Proteopedia - User contributions [en]

Sandbox Reserved 1662

2022-01-19T19:50:56Z

Daniel Jedlicka:

{{Sandbox_Reserved_ESBS20_}}
== '''UCP2''' ==

<Structure load='2lck' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

The uncoupling protein 2 (UCP2) protein is a transmembrane protein found in the mitochondria of various tissues such as white adipose tissue and muscle tissue. This protein allows uncoupling of the membrane electrochemical potential in the mitochondrial respiratory chain, resulting in heat generation. This protein is a carrier of protons and chlorides.The UCP2 protein is found in Homo sapiens and it is known under other names: BMIQ4, SLC25A8, UCPH. The gene coding for this protein is found on the chromosome 11 and has 5 transcripts for Homo sapiens.

== A transmembrane protein ==

The protein consists of 309 amino acids, with domains located in the mitochondrial matrix, the inner mitochondrial membrane and in the intermembrane mitochondrial space. More precisely it can be described as a chain of <scene name='86/868195/Transmembrane_helices/1'>six transmembrane helices</scene> and three amphipathic helices. The structure consists of three pseudo-repeats linking a transmembrane helix via a loop to an amphipathic helix, followed by another transmembrane alpha helix. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>

Transmembrane helices are mainly composed of hydrophobic amino acids containing lots of alanine, valine, and leucine. <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>
The determination and characterization of the structure of the membrane protein UCP2 was a difficulty that has been overcome thanks to a specific NMR method. This method combines two technics: the use of NMR residual dipolar couplings (RDCs) which give orientation restraints and Paramagnetic Relaxation Enhancement (PRE) which determines distance restraints. Experimental RDCs of UCP2 were compared to assemblies of known molecular fragments (from a Protein Data Bank) in order to determine local and secondary structures. Moreover, PRE restraints provide their spatial arrangement in the tertiary fold. <ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220743/pdf/10620491.pdf]Ricquier, D., Bouillaud, F., (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP</ref>

== An ion carrier protein ==

It is known that the electrochemical potential of the inner mitochondrial membrane is due to a proton gradient. UCP2 allows to translocate protons to the mitochondrial matrix (following the exergonic direction) and to couple the translocation with an emission of heat. However, the mechanism of this proton translocation is unknown. UCP2 moreover functions as a chloride carrier. Some experiments were performed to find out more about the structure associated with this transport, in particular the positively charged transmembrane alpha helix <scene name='86/868195/Tm2/1'>TM2</scene> (in the second pattern). Mutants were created lacking positive charged amino acids (arginine and lysine muted in glutamine): R76Q, R88Q, R96Q, and K104Q. After purification and insertion of those mutants in liposomes it has been observed that Cl- transport crucially decreases compared to the wild type. This positive alpha helix, therefore, is necessary to transport chloride-ions. <ref>[https://doi.org/10.1021/acs.biochem.5b00177]Hoang, T., Matovic, T., Parker, J., Smith, M.D., Jelokhani-Niaraki, M., Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2, Biochemistry 2015, 54, 14, 2303–2313, </ref>
Moreover these experiments have shown that the positively charged domain allows precipitation of salts resulting in a dense packing in UCP2. This conformation amplifies the proton transport rate.

== A regulated protein ==

Electron paramagnetic resonance studies showed conformational change in presence of long chain fatty acids. Fatty acids play a major role in the activation of the UCP2 protein. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>
Furthermore, it was observed that UCP2 is inhibited by GDP. Thus, a low cellular energy level will favor the production of ATP by the ATP synthase at the end of the respiratory chain instead of uncoupling. Some experiments with mutants have shown, that the GDP binding site is close to the <scene name='86/868195/Helices_1_and_4/1'>helices 1 and 4</scene> <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>

While the structure of the protein is now well known, the mechanisms of uncoupling are more difficult to study. Understanding how the uncoupling proteins work is a key topic, as these proteins play a role in diseases such as cancer or obesity.

<scene name='86/868195/Test/1'>TextToBeDisplayed</scene>

== References ==

<references/> Further information about this protein:
http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000175567;r=11:73974667-73983307
http://may2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000033685
https://www.proteinatlas.org/ENSG00000175567-UCP2/tissue
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7351
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCP2
https://datamed.org/display-item.php?repository=0002&id=5952dfd35152c64c3b10b93c&query=UCP2
https://humancyc.org/gene?orgid=HUMAN&id=HS10953

Sandbox Reserved 1662

2022-01-19T19:50:46Z

Daniel Jedlicka:

</nowiki>{{Sandbox_Reserved_ESBS20_}}
== '''UCP2''' ==

<Structure load='2lck' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

The uncoupling protein 2 (UCP2) protein is a transmembrane protein found in the mitochondria of various tissues such as white adipose tissue and muscle tissue. This protein allows uncoupling of the membrane electrochemical potential in the mitochondrial respiratory chain, resulting in heat generation. This protein is a carrier of protons and chlorides.The UCP2 protein is found in Homo sapiens and it is known under other names: BMIQ4, SLC25A8, UCPH. The gene coding for this protein is found on the chromosome 11 and has 5 transcripts for Homo sapiens.

== A transmembrane protein ==

The protein consists of 309 amino acids, with domains located in the mitochondrial matrix, the inner mitochondrial membrane and in the intermembrane mitochondrial space. More precisely it can be described as a chain of <scene name='86/868195/Transmembrane_helices/1'>six transmembrane helices</scene> and three amphipathic helices. The structure consists of three pseudo-repeats linking a transmembrane helix via a loop to an amphipathic helix, followed by another transmembrane alpha helix. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>

Transmembrane helices are mainly composed of hydrophobic amino acids containing lots of alanine, valine, and leucine. <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>
The determination and characterization of the structure of the membrane protein UCP2 was a difficulty that has been overcome thanks to a specific NMR method. This method combines two technics: the use of NMR residual dipolar couplings (RDCs) which give orientation restraints and Paramagnetic Relaxation Enhancement (PRE) which determines distance restraints. Experimental RDCs of UCP2 were compared to assemblies of known molecular fragments (from a Protein Data Bank) in order to determine local and secondary structures. Moreover, PRE restraints provide their spatial arrangement in the tertiary fold. <ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220743/pdf/10620491.pdf]Ricquier, D., Bouillaud, F., (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP</ref>

== An ion carrier protein ==

It is known that the electrochemical potential of the inner mitochondrial membrane is due to a proton gradient. UCP2 allows to translocate protons to the mitochondrial matrix (following the exergonic direction) and to couple the translocation with an emission of heat. However, the mechanism of this proton translocation is unknown. UCP2 moreover functions as a chloride carrier. Some experiments were performed to find out more about the structure associated with this transport, in particular the positively charged transmembrane alpha helix <scene name='86/868195/Tm2/1'>TM2</scene> (in the second pattern). Mutants were created lacking positive charged amino acids (arginine and lysine muted in glutamine): R76Q, R88Q, R96Q, and K104Q. After purification and insertion of those mutants in liposomes it has been observed that Cl- transport crucially decreases compared to the wild type. This positive alpha helix, therefore, is necessary to transport chloride-ions. <ref>[https://doi.org/10.1021/acs.biochem.5b00177]Hoang, T., Matovic, T., Parker, J., Smith, M.D., Jelokhani-Niaraki, M., Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2, Biochemistry 2015, 54, 14, 2303–2313, </ref>
Moreover these experiments have shown that the positively charged domain allows precipitation of salts resulting in a dense packing in UCP2. This conformation amplifies the proton transport rate.

== A regulated protein ==

Electron paramagnetic resonance studies showed conformational change in presence of long chain fatty acids. Fatty acids play a major role in the activation of the UCP2 protein. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>
Furthermore, it was observed that UCP2 is inhibited by GDP. Thus, a low cellular energy level will favor the production of ATP by the ATP synthase at the end of the respiratory chain instead of uncoupling. Some experiments with mutants have shown, that the GDP binding site is close to the <scene name='86/868195/Helices_1_and_4/1'>helices 1 and 4</scene> <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>

While the structure of the protein is now well known, the mechanisms of uncoupling are more difficult to study. Understanding how the uncoupling proteins work is a key topic, as these proteins play a role in diseases such as cancer or obesity.

<scene name='86/868195/Test/1'>TextToBeDisplayed</scene>

== References ==

<references/> Further information about this protein:
http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000175567;r=11:73974667-73983307
http://may2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000033685
https://www.proteinatlas.org/ENSG00000175567-UCP2/tissue
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7351
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCP2
https://datamed.org/display-item.php?repository=0002&id=5952dfd35152c64c3b10b93c&query=UCP2
https://humancyc.org/gene?orgid=HUMAN&id=HS10953

Sandbox Reserved 1662

2022-01-19T19:50:12Z

Daniel Jedlicka:

<nowiki>''Insert non-formatted text here''</nowiki>{{Sandbox_Reserved_ESBS20_}}
== '''UCP2''' ==

<Structure load='2lck' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

The uncoupling protein 2 (UCP2) protein is a transmembrane protein found in the mitochondria of various tissues such as white adipose tissue and muscle tissue. This protein allows uncoupling of the membrane electrochemical potential in the mitochondrial respiratory chain, resulting in heat generation. This protein is a carrier of protons and chlorides.The UCP2 protein is found in Homo sapiens and it is known under other names: BMIQ4, SLC25A8, UCPH. The gene coding for this protein is found on the chromosome 11 and has 5 transcripts for Homo sapiens.

== A transmembrane protein ==

The protein consists of 309 amino acids, with domains located in the mitochondrial matrix, the inner mitochondrial membrane and in the intermembrane mitochondrial space. More precisely it can be described as a chain of <scene name='86/868195/Transmembrane_helices/1'>six transmembrane helices</scene> and three amphipathic helices. The structure consists of three pseudo-repeats linking a transmembrane helix via a loop to an amphipathic helix, followed by another transmembrane alpha helix. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>

Transmembrane helices are mainly composed of hydrophobic amino acids containing lots of alanine, valine, and leucine. <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>
The determination and characterization of the structure of the membrane protein UCP2 was a difficulty that has been overcome thanks to a specific NMR method. This method combines two technics: the use of NMR residual dipolar couplings (RDCs) which give orientation restraints and Paramagnetic Relaxation Enhancement (PRE) which determines distance restraints. Experimental RDCs of UCP2 were compared to assemblies of known molecular fragments (from a Protein Data Bank) in order to determine local and secondary structures. Moreover, PRE restraints provide their spatial arrangement in the tertiary fold. <ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220743/pdf/10620491.pdf]Ricquier, D., Bouillaud, F., (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP</ref>

== An ion carrier protein ==

It is known that the electrochemical potential of the inner mitochondrial membrane is due to a proton gradient. UCP2 allows to translocate protons to the mitochondrial matrix (following the exergonic direction) and to couple the translocation with an emission of heat. However, the mechanism of this proton translocation is unknown. UCP2 moreover functions as a chloride carrier. Some experiments were performed to find out more about the structure associated with this transport, in particular the positively charged transmembrane alpha helix <scene name='86/868195/Tm2/1'>TM2</scene> (in the second pattern). Mutants were created lacking positive charged amino acids (arginine and lysine muted in glutamine): R76Q, R88Q, R96Q, and K104Q. After purification and insertion of those mutants in liposomes it has been observed that Cl- transport crucially decreases compared to the wild type. This positive alpha helix, therefore, is necessary to transport chloride-ions. <ref>[https://doi.org/10.1021/acs.biochem.5b00177]Hoang, T., Matovic, T., Parker, J., Smith, M.D., Jelokhani-Niaraki, M., Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2, Biochemistry 2015, 54, 14, 2303–2313, </ref>
Moreover these experiments have shown that the positively charged domain allows precipitation of salts resulting in a dense packing in UCP2. This conformation amplifies the proton transport rate.

== A regulated protein ==

Electron paramagnetic resonance studies showed conformational change in presence of long chain fatty acids. Fatty acids play a major role in the activation of the UCP2 protein. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>
Furthermore, it was observed that UCP2 is inhibited by GDP. Thus, a low cellular energy level will favor the production of ATP by the ATP synthase at the end of the respiratory chain instead of uncoupling. Some experiments with mutants have shown, that the GDP binding site is close to the <scene name='86/868195/Helices_1_and_4/1'>helices 1 and 4</scene> <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>

While the structure of the protein is now well known, the mechanisms of uncoupling are more difficult to study. Understanding how the uncoupling proteins work is a key topic, as these proteins play a role in diseases such as cancer or obesity.

<scene name='86/868195/Test/1'>TextToBeDisplayed</scene>

== References ==

<references/> Further information about this protein:
http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000175567;r=11:73974667-73983307
http://may2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000033685
https://www.proteinatlas.org/ENSG00000175567-UCP2/tissue
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7351
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCP2
https://datamed.org/display-item.php?repository=0002&id=5952dfd35152c64c3b10b93c&query=UCP2
https://humancyc.org/gene?orgid=HUMAN&id=HS10953

Sandbox Reserved 1662

2022-01-19T19:49:35Z

Daniel Jedlicka:

<nowiki>''Insert non-formatted text here''</nowiki>{{Sandbox_Reserved_ESBS20_}}
== '''UCP2''' ==

<Structure load='2lck' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

The uncoupling protein 2 (UCP2) protein is a transmembrane protein found in the mitochondria of various tissues such as white adipose tissue and muscle tissue. This protein allows uncoupling of the membrane electrochemical potential in the mitochondrial respiratory chain, resulting in heat generation. This protein is a carrier of protons and chlorides.The UCP2 protein is found in Homo sapiens and it is known under other names: BMIQ4, SLC25A8, UCPH. The gene coding for this protein is found on the chromosome 11 and has 5 transcripts for Homo sapiens.

== A transmembrane protein ==

The protein consists of 309 amino acids, with domains located in the mitochondrial matrix, the inner mitochondrial membrane and in the intermembrane mitochondrial space. More precisely it can be described as a chain of <scene name='86/868195/Transmembrane_helices/1'>six transmembrane helices</scene> and three amphipathic helices. The structure consists of three pseudo-repeats linking a transmembrane helix via a loop to an amphipathic helix, followed by another transmembrane alpha helix. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>

Transmembrane helices are mainly composed of hydrophobic amino acids containing lots of alanine, valine, and leucine. <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>
The determination and characterization of the structure of the membrane protein UCP2 was a difficulty that has been overcome thanks to a specific NMR method. This method combines two technics: the use of NMR residual dipolar couplings (RDCs) which give orientation restraints and Paramagnetic Relaxation Enhancement (PRE) which determines distance restraints. Experimental RDCs of UCP2 were compared to assemblies of known molecular fragments (from a Protein Data Bank) in order to determine local and secondary structures. Moreover, PRE restraints provide their spatial arrangement in the tertiary fold. <ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220743/pdf/10620491.pdf]Ricquier, D., Bouillaud, F., (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP</ref>

== An ion carrier protein ==

It is known that the electrochemical potential of the inner mitochondrial membrane is due to a proton gradient. UCP2 allows to translocate protons to the mitochondrial matrix (following the exergonic direction) and to couple the translocation with an emission of heat. However, the mechanism of this proton translocation is unknown. UCP2 moreover functions as a chloride carrier. Some experiments were performed to find out more about the structure associated with this transport, in particular the positively charged transmembrane alpha helix <scene name='86/868195/Tm2/1'>TM2</scene> (in the second pattern). Mutants were created lacking positive charged amino acids (arginine and lysine muted in glutamine): R76Q, R88Q, R96Q, and K104Q. After purification and insertion of those mutants in liposomes it has been observed that Cl- transport crucially decreases compared to the wild type. This positive alpha helix, therefore, is necessary to transport chloride-ions. <ref>[https://doi.org/10.1021/acs.biochem.5b00177]Hoang, T., Matovic, T., Parker, J., Smith, M.D., Jelokhani-Niaraki, M., Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2, Biochemistry 2015, 54, 14, 2303–2313, </ref>
Moreover these experiments have shown that the positively charged domain allows precipitation of salts resulting in a dense packing in UCP2. This conformation amplifies the proton transport rate.

== A regulated protein ==

Some electron paramagnetic resonance studies show a changement of conformation in presence of fatty acids with long chains. Fatty acids are necessary to the setting up of the active form of the UCP2. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>
It is also observed that the UCP2 is inhibited by GDP. In that a low cellular energy level will favor the production of ATP by the ATP synthase at the end of the respiratory chain instead of uncoupling. Some experiments with mutants show that the GDP binding site is closer to the <scene name='86/868195/Helices_1_and_4/1'>helices 1 and 4</scene> <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>

If the structure of the protein is today well known, the mechanisms of the uncoupling are harder to study. The understanding of the uncoupling proteins’ running is a key issue because those proteins are implicated in some diseases such as cancers or obesity.

<scene name='86/868195/Test/1'>TextToBeDisplayed</scene>

== References ==

<references/> Further information about this protein:
http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000175567;r=11:73974667-73983307
http://may2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000033685
https://www.proteinatlas.org/ENSG00000175567-UCP2/tissue
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7351
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCP2
https://datamed.org/display-item.php?repository=0002&id=5952dfd35152c64c3b10b93c&query=UCP2
https://humancyc.org/gene?orgid=HUMAN&id=HS10953

Sandbox Reserved 1662

2022-01-19T19:48:44Z

Daniel Jedlicka:

<nowiki>''Insert non-formatted text here''</nowiki>{{Sandbox_Reserved_ESBS20_}}
== '''UCP2''' ==

<Structure load='2lck' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

The uncoupling protein 2 (UCP2) protein is a transmembrane protein found in the mitochondria of various tissues such as white adipose tissue and muscle tissue. This protein allows uncoupling of the membrane electrochemical potential in the mitochondrial respiratory chain, resulting in heat generation. This protein is a carrier of protons and chlorides.The UCP2 protein is found in Homo sapiens and it is known under other names: BMIQ4, SLC25A8, UCPH. The gene coding for this protein is found on the chromosome 11 and has 5 transcripts for Homo sapiens.

== A transmembrane protein ==

The protein consists of 309 amino acids, with domains located in the mitochondrial matrix, the inner mitochondrial membrane and in the intermembrane mitochondrial space. More precisely it can be described as a chain of <scene name='86/868195/Transmembrane_helices/1'>six transmembrane helices</scene> and three amphipathic helices. The structure consists of three pseudo-repeats linking a transmembrane helix via a loop to an amphipathic helix, followed by another transmembrane alpha helix. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>

Transmembrane helices are mainly composed of hydrophobic amino acids containing lots of alanine, valine, and leucine. <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>
The determination and characterization of the structure of the membrane protein UCP2 was a difficulty that has been overcome thanks to a specific NMR method. This method combines two technics: the use of NMR residual dipolar couplings (RDCs) which give orientation restraints and Paramagnetic Relaxation Enhancement (PRE) which determines distance restraints. Experimental RDCs of UCP2 were compared to assemblies of known molecular fragments (from a Protein Data Bank) in order to determine local and secondary structures. Moreover, PRE restraints provide their spatial arrangement in the tertiary fold. <ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220743/pdf/10620491.pdf]Ricquier, D., Bouillaud, F., (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP</ref>

== An ion carrier protein ==

It is known that the electrochemical potential of the inner mitochondrial membrane is due to a proton gradient. UCP2 allows to translocate protons to the mitochondrial matrix (following the exergonic direction) and to couple that with heat emission. However, the mechanism of this proton translocation is unknown.
UCP2 is also a chloride carrier. Some experiments were carried out about the structure related to this transport particularly about the positively charged transmembrane alpha helix <scene name='86/868195/Tm2/1'>TM2</scene>(in the second pattern). Mutants were created without positive charged amino acids (arginine and lysine muted in glutamine) : R76Q, R88Q, R96Q, and K104Q. After purification and insertion of those mutants in liposomes it is observed that Cl- transport crucially decreases compared with the wild type. So this positive alpha helix is necessary to chloride transport. <ref>[https://doi.org/10.1021/acs.biochem.5b00177]Hoang, T., Matovic, T., Parker, J., Smith, M.D., Jelokhani-Niaraki, M., Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2, Biochemistry 2015, 54, 14, 2303–2313, </ref>
Those experiments also shown that this positively charged domain allows precipitation of salts resulting in a dense packing in UCP2. This conformation significantly increases the proton transport rate.

== A regulated protein ==

Some electron paramagnetic resonance studies show a changement of conformation in presence of fatty acids with long chains. Fatty acids are necessary to the setting up of the active form of the UCP2. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>
It is also observed that the UCP2 is inhibited by GDP. In that a low cellular energy level will favor the production of ATP by the ATP synthase at the end of the respiratory chain instead of uncoupling. Some experiments with mutants show that the GDP binding site is closer to the <scene name='86/868195/Helices_1_and_4/1'>helices 1 and 4</scene> <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>

If the structure of the protein is today well known, the mechanisms of the uncoupling are harder to study. The understanding of the uncoupling proteins’ running is a key issue because those proteins are implicated in some diseases such as cancers or obesity.

<scene name='86/868195/Test/1'>TextToBeDisplayed</scene>

== References ==

<references/> Further information about this protein:
http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000175567;r=11:73974667-73983307
http://may2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000033685
https://www.proteinatlas.org/ENSG00000175567-UCP2/tissue
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7351
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCP2
https://datamed.org/display-item.php?repository=0002&id=5952dfd35152c64c3b10b93c&query=UCP2
https://humancyc.org/gene?orgid=HUMAN&id=HS10953

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Daniel Jedlicka:

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== '''UCP2''' ==

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The uncoupling protein 2 (UCP2) protein is a transmembrane protein found in the mitochondria of various tissues such as white adipose tissue and muscle tissue. This protein allows uncoupling of the membrane electrochemical potential in the mitochondrial respiratory chain, resulting in heat generation. This protein is a carrier of protons and chlorides.The UCP2 protein is found in Homo sapiens and it is known under other names: BMIQ4, SLC25A8, UCPH. The gene coding for this protein is found on the chromosome 11 and has 5 transcripts for Homo sapiens.

== A transmembrane protein ==

UCP2 is 309 amino acids long with domains located in the mitochondrial matrix, in the inner mitochondrial membrane and in the intermembrane mitochondrial space.
More precisely it can be described as a chain of <scene name='86/868195/Transmembrane_helices/1'>six transmembrane helices</scene> and three amphipathic helices. The structure consists of three pseudo-repeats in which a transmembrane helix is linked by a loop to an amphipathic helix, followed by another transmembrane alpha helix.<ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>

In addition, transmembrane helices are mainly composed of hydrophobic amino acids with a lot of alanine, valine and leucine. <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>
Membrane-protein structure determination and characterisation of UCP2 is a difficulty which is overcomed thanks to a specific NMR method. This method combines two technics : first, the use of NMR residual dipolar couplings (RDCs) which give orientation restraints and Paramagnetic Relaxation Enhancement (PRE) which determines distance restraints. Experimental RDCs of UCP2 were compared to assemblies of known molecular fragments (from the Protein Data Bank) aiming the determination of the local and secondary structures. Moreover, PRE restraints provide their spatial arrangement in the tertiary fold. <ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220743/pdf/10620491.pdf]Ricquier, D., Bouillaud, F., (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP</ref>

== An ion carrier protein ==

It is known that the electrochemical potential of the inner mitochondrial membrane is due to a proton gradient. UCP2 allows to translocate protons to the mitochondrial matrix (following the exergonic direction) and to couple that with heat emission. However, the mechanism of this proton translocation is unknown.
UCP2 is also a chloride carrier. Some experiments were carried out about the structure related to this transport particularly about the positively charged transmembrane alpha helix <scene name='86/868195/Tm2/1'>TM2</scene>(in the second pattern). Mutants were created without positive charged amino acids (arginine and lysine muted in glutamine) : R76Q, R88Q, R96Q, and K104Q. After purification and insertion of those mutants in liposomes it is observed that Cl- transport crucially decreases compared with the wild type. So this positive alpha helix is necessary to chloride transport. <ref>[https://doi.org/10.1021/acs.biochem.5b00177]Hoang, T., Matovic, T., Parker, J., Smith, M.D., Jelokhani-Niaraki, M., Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2, Biochemistry 2015, 54, 14, 2303–2313, </ref>
Those experiments also shown that this positively charged domain allows precipitation of salts resulting in a dense packing in UCP2. This conformation significantly increases the proton transport rate.

== A regulated protein ==

Some electron paramagnetic resonance studies show a changement of conformation in presence of fatty acids with long chains. Fatty acids are necessary to the setting up of the active form of the UCP2. <ref>[https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/2/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)-_-/Ch20_Kream_E_Uncoupling_Protein_2_(Mitochondrial)_MitochondrialUncouplingProtein2.html]Kream, E., Mitochondrial uncoupling protein 2 </ref>
It is also observed that the UCP2 is inhibited by GDP. In that a low cellular energy level will favor the production of ATP by the ATP synthase at the end of the respiratory chain instead of uncoupling. Some experiments with mutants show that the GDP binding site is closer to the <scene name='86/868195/Helices_1_and_4/1'>helices 1 and 4</scene> <ref>[https://www.uniprot.org/uniprot/P70406] UniProtKB - P70406 UCP2_MOUSE </ref>

If the structure of the protein is today well known, the mechanisms of the uncoupling are harder to study. The understanding of the uncoupling proteins’ running is a key issue because those proteins are implicated in some diseases such as cancers or obesity.

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== References ==

<references/> Further information about this protein:
http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000175567;r=11:73974667-73983307
http://may2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000033685
https://www.proteinatlas.org/ENSG00000175567-UCP2/tissue
https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7351
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCP2
https://datamed.org/display-item.php?repository=0002&id=5952dfd35152c64c3b10b93c&query=UCP2
https://humancyc.org/gene?orgid=HUMAN&id=HS10953