Proteopedia - User contributions [en]

Prp19

2011-04-02T04:57:43Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-Ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18, which are associated with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play a role in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately thereafter. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged, involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a role in the specificity of the base pairing between U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T04:56:20Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18, which are associated with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play a role in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately thereafter. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged, involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a role in the specificity of the base pairing between U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T04:53:27Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18, which are associated with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play a role in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged, involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a role in the specificity of the base pairing between U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T04:52:04Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18, which are associated with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play a role in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged, involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a role in the specificity in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T04:49:48Z

Aaron Smith: /* Role in Splicing */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18, which are associated with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play a role in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T04:43:21Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T04:40:07Z

Aaron Smith:

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>.

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T00:45:17Z

Aaron Smith: /* Structure */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T00:40:52Z

Aaron Smith: /* Role in Splicing */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRNPs themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the di-snRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins, coined the nineteen complex, or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T00:37:24Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image above, as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-02T00:33:53Z

Aaron Smith: /* Introduction */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-01T04:20:50Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-01T04:19:19Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins<ref>pmid:11814058.</ref>. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-01T04:18:11Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref><ref>pmid:10322433</ref>. The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-01T04:14:37Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a specificity role in the base pairing of U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>

=References=

<references />

Prp19

2011-04-01T04:06:03Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller fold can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T04:04:58Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T04:04:01Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T04:00:19Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.<ref>pmid:16540691</ref>
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:58:58Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after.
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:51:24Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of [http://en.wikipedia.org/wiki/LSmLsm] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:49:43Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='Prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:47:51Z

Aaron Smith:

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==
[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='prp19/2bay'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:46:29Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='prp19/2bay/3'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:44:37Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name=2bay>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:38:10Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen <scene name='2bay'>here</scene>

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:36:50Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen [SCENE=2bayhere]

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:36:18Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen [SCENE= 2bayhere]

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:35:46Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen [ SCENE= 2bay }}here]

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:33:22Z

Aaron Smith: /* U-Box Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. The secondary structure can be seen [{{STRUCTURE_2bay | PDB=2bay | SCENE= }}here]

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:31:53Z

Aaron Smith:

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19. {{STRUCTURE_2bay | PDB=2bay | SCENE= }}

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T03:29:45Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. The Beta Propeller structure can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form a Beta Propeller fold which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Blade repeats can often be used as platforms for binding of other proteins or ligands.<ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The propeller fold in PRP19's WD40 domain is comprised of seven blades and is asymmetrical due to a slight distortion in blades one and seven. The region around blade five is highly conserved and is necessary for interaction between PRP19 and Cwc2, another splicing factor found in the NTC. The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T02:36:41Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
Research has shown that PRP19 is required for a reaction in which the structure of the U6 snRNP is re-arranged involving destabilization of Lsm proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.

<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T02:35:54Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
<ref>PMID:16540691</ref>

=References=

<references />

Prp19

2011-04-01T02:34:56Z

Aaron Smith: /* The Nineteen Complex */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=
<ref>PMID:1086602</ref>

=References=

<references />

Prp19

2011-04-01T02:25:52Z

Aaron Smith:

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=The Nineteen Complex=

=References=

<references />

Prp19

2011-04-01T02:24:40Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:23:35Z

Aaron Smith: /* Structure */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref name="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="Wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:23:11Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="Wd40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:22:32Z

Aaron Smith: /* Structure */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref="wd40domain">pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.<ref name="Wed40domain"/>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:19:38Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref>pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref> The WD40 domain of PRP19 is found between residues 165 and 503. Its structure was solved in 2010 by X-Ray diffraction at a resolution of 2.6 Angstroms.

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:16:59Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref>pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] Secondary Structure of the WD40 Domain of PRP19. Beta Propeller structures can be seen.

WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:15:45Z

Aaron Smith: /* WD40 Domain */

{{STRUCTURE_3lrv | PDB=3lrv | SCENE= }}

==Introduction==
PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers Zinc fingers], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref>. However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.
<ref name="novel"/>

=Structure=
In Humans, the gene which is homologous to that of PRP19 in ''S. cerevisiae'' is located on chromosome 11 (11q12.2).<ref>"Entrez Gene: PRPF19 PRP19/PSO4 pre-mRNA processing factor 19 homolog (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27339.</ref> The protein is 503 amino acid residues in length and forms a tetramer with a centrally coiled domain<Ref name="something">PMID:16388587</ref>. The protein was found to have a molecular weight of 56 kDa <ref>pmid:17276391</ref>Two majors functional domains have been identified, the [http://proteopedia.com/wiki/index.php/3lrv WD40 domain] and the [http://proteopedia.com/wiki/index.php/2bay U Box domain]<ref>pmid:20462492</ref>

==U-Box Domain==

[[Image:2bay_small.jpg]] This is a CPK coloured representation of the U Box Domain of PRP19

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bond and or salt bridges. In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/> The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via xray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

==WD40 Domain==
[[Image:3lrv_small.jpg]] This is a CPK coloured representation of the WD40 Domain of PRP19.

[[Image:3LRV_-_secondary_small.jpg]] WD40 domains can be found throughout a large variety of organisms and are highly abundant in eukaryotic proteins. WD40 domains can have several functions including cell cycle control, involvement in signal transduction, assembly of the cytoskeleton, gene transcriptional activiation and pre mRNA processing. Conserved repeats ~40 residues long, consisting of tryptophan and aspartic acid residues, form Beta Propeller structures which can be seen in the image to the left as well as in the default scene image. The default scene also shows 4 SO4 molecules binding which help to activate the complex. Beta Propeller repeats can often as as platforms for binding of other proteins or ligands. <ref>http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=190</ref>

=Role in Splicing=
Research has shown that different PRP proteins are involved in splicing in very different ways. For instance, some PRP proteins are directly associated with snRNPs (snurps) such as PRP8 and PRP18's with the [http://en.wikipedia.org/wiki/U5_snRNA U5] snRNP. Others interact with with snRNA at different times, such as PRP17 and PRP18 with U5, which are thought to play a functional role. Certain PRP proteins are involved in specific steps, such as PRP2's involvement in the first cleavage / ligation reaction. Furthermore, some PRPs play roles in snRNP binding. That is, PRP9, PRP11 and PRP21 are thought to help promote U2 binding early on in the spliceosomal assembly process. <ref name ="functional"/> Another important role of PRP proteins is helping to anneal the snRPS themselves. An example of this is [http://proteopedia.com/wiki/index.php/Sandbox_Reserved_340 PRP24] aiding in the association of U4 and U6, which form the disnRNP<ref name ="guthriescience">PMID 9452384</ref>.

Studies have found that PRP19 associates with the spliceosome around the time that the U4 snRNP disassociates from the complex. This is thought to be evidence towards PRP19's involvement in the conformational rearrangement that occurs at this stage of the splicing process.<ref name ="functional"/> Other evidence suggests that PRP19 acts to stabilize the association of U5 and U6 with the active spliceosome. Researchers have also suggested that PRP19 is part of a heteromeric complex which is comprised of at least eight different proteins,coined the nineteen complex or NTC.<ref name ="2004EMBO">PMID:15175653</ref> There is also evidence that PRP19 may be part of an even larger complex consisting of the U2, U5 and U6 snRNA as well as many other proteins.<ref name="ohi">PMID:12088152</ref>

=References=

<references />

Prp19

2011-04-01T02:09:46Z

Aaron Smith: /* WD40 Domain */

Prp19

2011-04-01T02:09:28Z

Aaron Smith: /* WD40 Domain */

Prp19

2011-04-01T02:09:02Z

Aaron Smith: /* WD40 Domain */

Prp19

2011-04-01T02:07:02Z

Aaron Smith: /* WD40 Domain */

File:3LRV - secondary small.jpg

2011-04-01T02:06:07Z

Aaron Smith:

Prp19

2011-04-01T01:26:56Z

Aaron Smith: /* WD40 Domain */

Prp19

2011-04-01T01:26:10Z

Aaron Smith: /* WD40 Domain */