3egu - Revision history

OCA at 09:47, 21 February 2024

2024-02-21T09:47:39Z

← Older revision		Revision as of 09:47, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3egu' size='340' side='right'caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='3egu' size='340' side='right'caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EGU FirstGlance]. <br>		<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EGU FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.25Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em~~;~~'>[[2o88\|2o88]], [[1bbz\|1bbz]], [[3eg0\|3eg0]], [[3eg1\|3eg1]], [[3eg2\|3eg2]], [[3eg3\|3eg3]]</div>~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>ABL1, ABL, JTK7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~
	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2]~~ </~~span~~></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [https://pdbe.org/3egu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [https://www.ebi.ac.uk/pdbsum/3egu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3egu ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [https://pdbe.org/3egu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [https://www.ebi.ac.uk/pdbsum/3egu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3egu ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).		[https://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref> <ref>PMID:9144171</ref> <ref>PMID:9461559</ref> <ref>PMID:10391250</ref> <ref>PMID:12379650</ref> <ref>PMID:11971963</ref> <ref>PMID:12531427</ref> <ref>PMID:12672821</ref> <ref>PMID:15556646</ref> <ref>PMID:15031292</ref> <ref>PMID:15886098</ref> <ref>PMID:15657060</ref> <ref>PMID:16943190</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:17623672</ref> <ref>PMID:18328268</ref> <ref>PMID:18945674</ref> <ref>PMID:19891780</ref> <ref>PMID:20417104</ref> <ref>PMID:16424036</ref> <ref>PMID:20357770</ref>		[https://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref> <ref>PMID:9144171</ref> <ref>PMID:9461559</ref> <ref>PMID:10391250</ref> <ref>PMID:12379650</ref> <ref>PMID:11971963</ref> <ref>PMID:12531427</ref> <ref>PMID:12672821</ref> <ref>PMID:15556646</ref> <ref>PMID:15031292</ref> <ref>PMID:15886098</ref> <ref>PMID:15657060</ref> <ref>PMID:16943190</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:17623672</ref> <ref>PMID:18328268</ref> <ref>PMID:18945674</ref> <ref>PMID:19891780</ref> <ref>PMID:20417104</ref> <ref>PMID:16424036</ref> <ref>PMID:20357770</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3egu ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3egu ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The interaction of Abl-Src homology 3 domain (SH3) with the high affinity peptide p41 is the most notable example of the inconsistency existing between the currently accepted description of SH3 complexes and their binding thermodynamic signature. We had previously hypothesized that the presence of interfacial water molecules is partially responsible for this thermodynamic behavior. We present here a thermodynamic, structural, and molecular dynamics simulation study of the interaction of p41 with Abl-SH3 and a set of mutants designed to alter the water-mediated interaction network. Our results provide a detailed description of the dynamic properties of the interfacial water molecules and a molecular interpretation of the thermodynamic effects elicited by the mutations in terms of the modulation of the water-mediated hydrogen bond network. In the light of these results, a new dual binding mechanism is proposed that provides a better description of proline-rich ligand recognition by Abl-SH3 and that has important implications for rational design.

	Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl.,Palencia A, Camara-Artigas A, Pisabarro MT, Martinez JC, Luque I J Biol Chem. 2010 Jan 22;285(4):2823-33. Epub 2009 Nov 10. PMID:19906645<ref>PMID:19906645</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3egu" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific protein-tyrosine kinase]]~~		[[Category: Camara-Artigas A]]
	[[Category: Camara-Artigas, A]]
	~~[[Category: Atp-binding]]~~
	~~[[Category: Beta]]~~
	~~[[Category: Cell adhesion]]~~
	~~[[Category: Cytoskeleton]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Lipoprotein]]~~
	~~[[Category: Magnesium]]~~
	~~[[Category: Manganese]]~~
	~~[[Category: Metal-binding]]~~
	~~[[Category: Myristate]]~~
	~~[[Category: Nucleotide-binding]]~~
	~~[[Category: Nucleus]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Proto-oncogene]]~~
	~~[[Category: Sh2 domain]]~~
	~~[[Category: Sh3 domain]]~~
	~~[[Category: Transferase]]~~
	~~[[Category: Tyrosine-protein kinase~~]]

OCA at 19:40, 20 October 2021

2021-10-20T19:40:03Z

← Older revision		Revision as of 19:40, 20 October 2021
Line 1:		Line 1:

	==Crystal structure of the N114A mutant of ABL-SH3 domain==		==Crystal structure of the N114A mutant of ABL-SH3 domain==
	<StructureSection load='3egu' size='340' side='right' caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='3egu' size='340' side='right'caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3EGU FirstGlance]. <br>		<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EGU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2o88\|2o88]], [[1bbz\|1bbz]], [[3eg0\|3eg0]], [[3eg1\|3eg1]], [[3eg2\|3eg2]], [[3eg3\|3eg3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2o88\|2o88]], [[1bbz\|1bbz]], [[3eg0\|3eg0]], [[3eg1\|3eg1]], [[3eg2\|3eg2]], [[3eg3\|3eg3]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [~~http~~://pdbe.org/3egu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3egu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3egu ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [https://pdbe.org/3egu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [https://www.ebi.ac.uk/pdbsum/3egu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3egu ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).		[[https://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref> <ref>PMID:9144171</ref> <ref>PMID:9461559</ref> <ref>PMID:10391250</ref> <ref>PMID:12379650</ref> <ref>PMID:11971963</ref> <ref>PMID:12531427</ref> <ref>PMID:12672821</ref> <ref>PMID:15556646</ref> <ref>PMID:15031292</ref> <ref>PMID:15886098</ref> <ref>PMID:15657060</ref> <ref>PMID:16943190</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:17623672</ref> <ref>PMID:18328268</ref> <ref>PMID:18945674</ref> <ref>PMID:19891780</ref> <ref>PMID:20417104</ref> <ref>PMID:16424036</ref> <ref>PMID:20357770</ref>		[[https://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref> <ref>PMID:9144171</ref> <ref>PMID:9461559</ref> <ref>PMID:10391250</ref> <ref>PMID:12379650</ref> <ref>PMID:11971963</ref> <ref>PMID:12531427</ref> <ref>PMID:12672821</ref> <ref>PMID:15556646</ref> <ref>PMID:15031292</ref> <ref>PMID:15886098</ref> <ref>PMID:15657060</ref> <ref>PMID:16943190</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:17623672</ref> <ref>PMID:18328268</ref> <ref>PMID:18945674</ref> <ref>PMID:19891780</ref> <ref>PMID:20417104</ref> <ref>PMID:16424036</ref> <ref>PMID:20357770</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3egu_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3egu_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 33:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 3egu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3egu" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Camara-Artigas, A]]		[[Category: Camara-Artigas, A]]

OCA at 09:11, 25 October 2017

2017-10-25T09:11:00Z

← Older revision		Revision as of 09:11, 25 October 2017
Line 1:		Line 1:

	==Crystal structure of the N114A mutant of ABL-SH3 domain==		==Crystal structure of the N114A mutant of ABL-SH3 domain==
	<StructureSection load='3egu' size='340' side='right' caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='3egu' size='340' side='right' caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [http://pdbe.org/3egu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [http://www.ebi.ac.uk/pdbsum/3egu PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [http://pdbe.org/3egu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [http://www.ebi.ac.uk/pdbsum/3egu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3egu ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 32:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 3egu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3egu" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Tyrosine kinase\|Tyrosine kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 02:21, 10 February 2016

2016-02-10T02:21:31Z

← Older revision		Revision as of 02:21, 10 February 2016
Line 2:		Line 2:
	<StructureSection load='3egu' size='340' side='right' caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='3egu' size='340' side='right' caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EGU FirstGlance]. <br>		<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EGU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2o88\|2o88]], [[1bbz\|1bbz]], [[3eg0\|3eg0]], [[3eg1\|3eg1]], [[3eg2\|3eg2]], [[3eg3\|3eg3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2o88\|2o88]], [[1bbz\|1bbz]], [[3eg0\|3eg0]], [[3eg1\|3eg1]], [[3eg2\|3eg2]], [[3eg3\|3eg3]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [http://www.ebi.ac.uk/pdbsum/3egu PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [http://pdbe.org/3egu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [http://www.ebi.ac.uk/pdbsum/3egu PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3egu ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 31:		Line 31:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3egu" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Camara-Artigas, A]]		[[Category: Camara-Artigas, A]]

OCA at 14:26, 18 December 2014

2014-12-18T14:26:35Z

← Older revision		Revision as of 14:26, 18 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3egu\| PDB=3egu \| SCENE= }}~~		==Crystal structure of the N114A mutant of ABL-SH3 domain==
	===Crystal structure of the N114A mutant of ABL-SH3 domain===		<StructureSection load='3egu' size='340' side='right' caption='[[3egu]], [[Resolution\|resolution]] 2.25Å' scene=''>
	~~{{ABSTRACT_PUBMED_19906645}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3egu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EGU FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2o88\|2o88]], [[1bbz\|1bbz]], [[3eg0\|3eg0]], [[3eg1\|3eg1]], [[3eg2\|3eg2]], [[3eg3\|3eg3]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL1, ABL, JTK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3egu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3egu RCSB], [http://www.ebi.ac.uk/pdbsum/3egu PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).		[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
			== Function ==
			[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref> <ref>PMID:9144171</ref> <ref>PMID:9461559</ref> <ref>PMID:10391250</ref> <ref>PMID:12379650</ref> <ref>PMID:11971963</ref> <ref>PMID:12531427</ref> <ref>PMID:12672821</ref> <ref>PMID:15556646</ref> <ref>PMID:15031292</ref> <ref>PMID:15886098</ref> <ref>PMID:15657060</ref> <ref>PMID:16943190</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:17623672</ref> <ref>PMID:18328268</ref> <ref>PMID:18945674</ref> <ref>PMID:19891780</ref> <ref>PMID:20417104</ref> <ref>PMID:16424036</ref> <ref>PMID:20357770</ref>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3egu_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The interaction of Abl-Src homology 3 domain (SH3) with the high affinity peptide p41 is the most notable example of the inconsistency existing between the currently accepted description of SH3 complexes and their binding thermodynamic signature. We had previously hypothesized that the presence of interfacial water molecules is partially responsible for this thermodynamic behavior. We present here a thermodynamic, structural, and molecular dynamics simulation study of the interaction of p41 with Abl-SH3 and a set of mutants designed to alter the water-mediated interaction network. Our results provide a detailed description of the dynamic properties of the interfacial water molecules and a molecular interpretation of the thermodynamic effects elicited by the mutations in terms of the modulation of the water-mediated hydrogen bond network. In the light of these results, a new dual binding mechanism is proposed that provides a better description of proline-rich ligand recognition by Abl-SH3 and that has important implications for rational design.

	~~==Function==~~		Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl.,Palencia A, Camara-Artigas A, Pisabarro MT, Martinez JC, Luque I J Biol Chem. 2010 Jan 22;285(4):2823-33. Epub 2009 Nov 10. PMID:19906645<ref>PMID:19906645</ref>
	[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of ~~proteins controlling cytoskeleton dynamics like WASF3 (involved~~ in ~~branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule~~-~~binding proteins). Phosphorylation of WASF3 is critical for~~ the ~~stimulation~~ of ~~lamellipodia formation and cell migration~~. ~~Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1~~, ~~CRK~~, ~~CRKL~~, ~~DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR~~, ~~facilitates the formation of neuromuscular synapses through MUSK~~, ~~inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes~~. ~~Other substrates which are involved in endocytosis regulation are the caveolin~~ (~~CAV1~~) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-~~induced apoptosis~~. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref><ref>PMID:9144171</ref><ref>PMID:9461559</ref><ref>PMID:10391250</ref><ref>PMID:12379650</ref><ref>PMID:11971963</ref><ref>PMID:12531427</ref><ref>PMID:12672821</ref><ref>PMID:15556646</ref><ref>PMID:15031292</ref><ref>PMID:15886098</ref><ref>PMID:15657060</ref><ref>PMID:16943190</ref><ref>PMID:16678104</ref><ref>PMID:17306540</ref><ref>PMID:17623672</ref><ref>PMID:18328268</ref><ref>PMID:18945674</ref><ref>PMID:19891780</ref><ref>PMID:20417104</ref><ref>PMID:16424036</ref><ref>PMID:~~20357770~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[3egu]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:/~~/~~oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].~~		</div>

	==See Also==		==See Also==
	*[[~~Proto-oncogene tyrosine-protein~~ kinase\|~~Proto-oncogene tyrosine-protein~~ kinase]]		*[[Tyrosine kinase\|Tyrosine kinase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:019906645</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Camara-Artigas, A.]]		[[Category: Camara-Artigas, A]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Beta]]		[[Category: Beta]]

OCA at 22:38, 24 March 2013

2013-03-24T22:38:44Z

← Older revision		Revision as of 22:38, 24 March 2013
Line 1:		Line 1:
	~~[[Image:3egu.png\|left\|200px]]~~

	{{STRUCTURE_3egu\| PDB=3egu \| SCENE= }}		{{STRUCTURE_3egu\| PDB=3egu \| SCENE= }}
			===Crystal structure of the N114A mutant of ABL-SH3 domain===
			{{ABSTRACT_PUBMED_19906645}}

	===~~Crystal structure of the N114A mutant~~ of ABL~~-SH3 domain===~~		==Disease==
			[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

	~~{{ABSTRACT_PUBMED_19906645}}~~		==Function==
			[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref><ref>PMID:9144171</ref><ref>PMID:9461559</ref><ref>PMID:10391250</ref><ref>PMID:12379650</ref><ref>PMID:11971963</ref><ref>PMID:12531427</ref><ref>PMID:12672821</ref><ref>PMID:15556646</ref><ref>PMID:15031292</ref><ref>PMID:15886098</ref><ref>PMID:15657060</ref><ref>PMID:16943190</ref><ref>PMID:16678104</ref><ref>PMID:17306540</ref><ref>PMID:17623672</ref><ref>PMID:18328268</ref><ref>PMID:18945674</ref><ref>PMID:19891780</ref><ref>PMID:20417104</ref><ref>PMID:16424036</ref><ref>PMID:20357770</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
	<ref group="xtra">PMID:019906645</ref><references group="xtra"/>		<ref group="xtra">PMID:019906645</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 15:59, 20 October 2012

2012-10-20T15:59:18Z

← Older revision		Revision as of 15:59, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[3egu]] is a 1 chain structure ~~of [[Proto-oncogene tyrosine-protein kinase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].		[[3egu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].

	==See Also==		==See Also==

OCA: Protected "3egu" [edit=sysop:move=sysop]

2012-07-26T20:13:44Z

Protected "3egu" [edit=sysop:move=sysop]

← Older revision	Revision as of 20:13, 26 July 2012
(No difference)

OCA at 20:13, 26 July 2012

2012-07-26T20:13:43Z

← Older revision		Revision as of 20:13, 26 July 2012
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	~~{{Seed}}~~
	[[Image:3egu.png\|left\|200px]]		[[Image:3egu.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3egu", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_3egu\| PDB=3egu \| SCENE= }}		{{STRUCTURE_3egu\| PDB=3egu \| SCENE= }}

	===Crystal structure of the N114A mutant of ABL-SH3 domain===		===Crystal structure of the N114A mutant of ABL-SH3 domain===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_19906645}}, adds the Publication Abstract to the page~~
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	~~-->~~
	{{ABSTRACT_PUBMED_19906645}}		{{ABSTRACT_PUBMED_19906645}}

	==About this Structure==		==About this Structure==
	~~3EGU~~ is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].		[[3egu]] is a 1 chain structure of [[Proto-oncogene tyrosine-protein kinase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].

			==See Also==
			*[[Proto-oncogene tyrosine-protein kinase\|Proto-oncogene tyrosine-protein kinase]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~19906645~~</ref><references group="xtra"/>		<ref group="xtra">PMID:019906645</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Camara-Artigas, A.]]		[[Category: Camara-Artigas, A.]]
	~~[[Category: Alternative splicing]]~~
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Beta]]		[[Category: Beta]]
	[[Category: Cell adhesion]]		[[Category: Cell adhesion]]
	~~[[Category: Chromosomal rearrangement]]~~
	~~[[Category: Cytoplasm]]~~
	[[Category: Cytoskeleton]]		[[Category: Cytoskeleton]]
	[[Category: Kinase]]		[[Category: Kinase]]
Line 43:		Line 31:
	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	~~[[Category: Polymorphism]]~~
	[[Category: Proto-oncogene]]		[[Category: Proto-oncogene]]
	[[Category: Sh2 domain]]		[[Category: Sh2 domain]]
Line 49:		Line 36:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Tyrosine-protein kinase]]		[[Category: Tyrosine-protein kinase]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 17 10:01:49 2010''~~

OCA at 08:01, 17 February 2010

2010-02-17T08:01:50Z

← Older revision		Revision as of 08:01, 17 February 2010
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
	[[Image:3egu.~~jpg~~\|left\|200px]]		[[Image:3egu.png\|left\|200px]]

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	===Crystal structure of the N114A mutant of ABL-SH3 domain===		===Crystal structure of the N114A mutant of ABL-SH3 domain===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_19906645}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 19906645 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_19906645}}

	==About this Structure==		==About this Structure==
	3EGU is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].		3EGU is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGU OCA].

			==Reference==
			<ref group="xtra">PMID:19906645</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
Line 41:		Line 50:
	[[Category: Tyrosine-protein kinase]]		[[Category: Tyrosine-protein kinase]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Sep 16 09~~:07:49 ~~2009~~''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 17 10:01:49 2010''