4eih - Revision history

OCA at 15:02, 14 March 2024

2024-03-14T15:02:20Z

← Older revision		Revision as of 15:02, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EIH FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EIH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.2Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [https://pdbe.org/4eih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [https://www.ebi.ac.uk/pdbsum/4eih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eih 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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [https://pdbe.org/4eih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [https://www.ebi.ac.uk/pdbsum/4eih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eih ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN]] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>		[https://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The closely related Abl family kinases, Arg and Abl, play important non-redundant roles in the regulation of cell morphogenesis and motility. Despite similar N-terminal sequences, Arg and Abl interact with different substrates and binding partners with varying affinities. This selectivity may be due to slight differences in amino acid sequence leading to differential interactions with target proteins. We report that the Arg Src homology (SH) 2 domain binds two specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10-fold higher affinity than the Abl SH2 domain. We show that this significant affinity difference is due to the substitution of arginine 161 and serine 187 in Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2 domains with R161L and S187T mutations alone and in combination and find that these substitutions are sufficient to convert the low affinity Abl SH2 domain to a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin peptide. We crystallized the Arg SH2 domain for structural comparison to existing crystal structures of the Abl SH2 domain. We show that these two residues are important determinants of Arg and Abl SH2 domain binding specificity. Finally, we expressed Arg containing an "Abl-like" low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, although properly localized to the cell periphery, does not support wild type levels of cell edge protrusion. Together, these observations indicate that these two amino acid positions confer different binding affinities and cellular functions on the distinct Abl family kinases.

	Two amino Acid residues confer different binding affinities of abelson family kinase SRC homology 2 domains for phosphorylated cortactin.,Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ J Biol Chem. 2014 Jul 11;289(28):19704-13. doi: 10.1074/jbc.M114.556480. Epub, 2014 Jun 2. PMID:24891505<ref>PMID:24891505</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4eih" style="background-color:#fffaf0;"></div~~>

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

OCA at 07:12, 28 September 2022

2022-09-28T07:12:45Z

← Older revision		Revision as of 07:12, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of Arg SH2 domain==		==Crystal structure of Arg SH2 domain==
	<StructureSection load='4eih' size='340' side='right' caption='[[4eih]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='4eih' size='340' side='right'caption='[[4eih]], [[Resolution\|resolution]] 1.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EIH FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EIH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL2, ABLL, ARG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [https://pdbe.org/4eih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [https://www.ebi.ac.uk/pdbsum/4eih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eih ProSAT]</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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [~~http~~://pdbe.org/4eih PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4eih PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4eih ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN]] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>		[[https://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN]] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Non-specific protein-tyrosine kinase~~]]		[[Category: Large Structures]]
	[[Category: Boggon~~, T J~~]]		[[Category: Boggon TJ]]
	[[Category: Koleske~~, A J~~]]		[[Category: Koleske AJ]]
	[[Category: Liu, W]]		[[Category: Liu W]]
	[[Category: MacGrath~~, S M]]~~		[[Category: MacGrath SM]]
	~~[[Category: Phosphopeptide]]~~
	~~[[Category: Phosphotyrosine]]~~
	~~[[Category: Protein/protein interaction]]~~
	~~[[Category: Sh2 domain]]~~
	~~[[Category: Transferase~~]]

OCA at 00:05, 5 August 2016

2016-08-05T00:05:26Z

← Older revision		Revision as of 00:05, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of Arg SH2 domain==		==Crystal structure of Arg SH2 domain==
	<StructureSection load='4eih' size='340' side='right' caption='[[4eih]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='4eih' size='340' side='right' caption='[[4eih]], [[Resolution\|resolution]] 1.20Å' scene=''>
Line 6:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL2, ABLL, ARG ([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">ABL2, ABLL, ARG ([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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih 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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://pdbe.org/4eih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eih ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4eih" style="background-color:#fffaf0;"></div>

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

OCA at 14:14, 25 December 2014

2014-12-25T14:14:45Z

← Older revision		Revision as of 14:14, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EIH FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EIH FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL2, ABLL, ARG ([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">ABL2, ABLL, ARG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih 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=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN]] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Boggon, T J.]]		[[Category: Boggon, T J]]
	[[Category: Koleske, A J.]]		[[Category: Koleske, A J]]
	[[Category: Liu, W.]]		[[Category: Liu, W]]
	[[Category: MacGrath, S M.]]		[[Category: MacGrath, S M]]
	[[Category: Phosphopeptide]]		[[Category: Phosphopeptide]]
	[[Category: Phosphotyrosine]]		[[Category: Phosphotyrosine]]

OCA at 06:38, 30 July 2014

2014-07-30T06:38:24Z

← Older revision		Revision as of 06:38, 30 July 2014
Line 8:		Line 8:
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum]</span></td></tr>		<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum]</span></td></tr>
	<table>		<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The closely related Abl family kinases, Arg and Abl, play important non-redundant roles in the regulation of cell morphogenesis and motility. Despite similar N-terminal sequences, Arg and Abl interact with different substrates and binding partners with varying affinities. This selectivity may be due to slight differences in amino acid sequence leading to differential interactions with target proteins. We report that the Arg Src homology (SH) 2 domain binds two specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10-fold higher affinity than the Abl SH2 domain. We show that this significant affinity difference is due to the substitution of arginine 161 and serine 187 in Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2 domains with R161L and S187T mutations alone and in combination and find that these substitutions are sufficient to convert the low affinity Abl SH2 domain to a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin peptide. We crystallized the Arg SH2 domain for structural comparison to existing crystal structures of the Abl SH2 domain. We show that these two residues are important determinants of Arg and Abl SH2 domain binding specificity. Finally, we expressed Arg containing an "Abl-like" low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, although properly localized to the cell periphery, does not support wild type levels of cell edge protrusion. Together, these observations indicate that these two amino acid positions confer different binding affinities and cellular functions on the distinct Abl family kinases.

			Two amino Acid residues confer different binding affinities of abelson family kinase SRC homology 2 domains for phosphorylated cortactin.,Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ J Biol Chem. 2014 Jul 11;289(28):19704-13. doi: 10.1074/jbc.M114.556480. Epub, 2014 Jun 2. PMID:24891505<ref>PMID:24891505</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

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

OCA at 06:44, 11 June 2014

2014-06-11T06:44:24Z

← Older revision		Revision as of 06:44, 11 June 2014
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	~~{{STRUCTURE_4eih~~\| ~~PDB~~=4eih \| ~~SCENE~~= }}		==Crystal structure of Arg SH2 domain==
	===~~Crystal structure of Arg SH2 domain~~===		<StructureSection load='4eih' size='340' side='right' caption='[[4eih]], [[Resolution\|resolution]] 1.20Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4eih]] 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=4EIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EIH FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene><br>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABL2, ABLL, ARG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
			<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum]</span></td></tr>
			<table>

	==~~Function~~==		==See Also==
	[[~~http://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN]] Non-receptor tyrosine-protein~~ kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>		*[[Tyrosine kinase\|Tyrosine kinase]]
			__TOC__
	~~==About this Structure==~~		</StructureSection>
	~~[[4eih~~]] 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=4EIH OCA].		[[Category: Human]]

	~~==Reference==~~
	~~<references group="xtra"/>~~<~~references~~/>
	[[Category: ~~Homo sapiens~~]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Boggon, T J.]]		[[Category: Boggon, T J.]]

OCA at 22:40, 10 April 2013

2013-04-10T22:40:43Z

← Older revision		Revision as of 22:40, 10 April 2013
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	~~'''Unreleased~~ structure~~'''~~		{{STRUCTURE_4eih\| PDB=4eih \| SCENE= }}
			===Crystal structure of Arg SH2 domain===

	~~The entry 4eih is ON HOLD~~ ~~until Apr 05 2014~~		==Function==
			[[http://www.uniprot.org/uniprot/ABL2_HUMAN ABL2_HUMAN]] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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:15886098</ref> <ref>PMID:15735735</ref> <ref>PMID:16678104</ref> <ref>PMID:17306540</ref> <ref>PMID:18945674</ref>

	~~Authors~~: ~~Liu, W~~.~~, MacGrath, S~~.M.~~, Koleske, A~~.J.~~, Boggon, T~~.J.		==About this Structure==
			[[4eih]] 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=4EIH OCA].

	~~Description~~:		==Reference==
			<references group="xtra"/><references/>
			[[Category: Homo sapiens]]
			[[Category: Non-specific protein-tyrosine kinase]]
			[[Category: Boggon, T J.]]
			[[Category: Koleske, A J.]]
			[[Category: Liu, W.]]
			[[Category: MacGrath, S M.]]
			[[Category: Phosphopeptide]]
			[[Category: Phosphotyrosine]]
			[[Category: Protein/protein interaction]]
			[[Category: Sh2 domain]]
			[[Category: Transferase]]

OCA at 16:07, 20 March 2013

2013-03-20T16:07:06Z

← Older revision		Revision as of 16:07, 20 March 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4eih is ON HOLD until ~~Paper Publication~~		The entry 4eih is ON HOLD until Apr 05 2014

	Authors: Liu, W., MacGrath, S.M., Koleske, A.J., Boggon, T.J.		Authors: Liu, W., MacGrath, S.M., Koleske, A.J., Boggon, T.J.

	Description:		Description:

OCA at 07:32, 18 April 2012

2012-04-18T07:32:01Z

← Older revision		Revision as of 07:32, 18 April 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4eih is ON HOLD		The entry 4eih is ON HOLD until Paper Publication

	Authors: Liu, W., MacGrath, S.M., Koleske, A.J., Boggon, T.J.		Authors: Liu, W., MacGrath, S.M., Koleske, A.J., Boggon, T.J.

	Description: ~~Protein X~~		Description:

OCA: Protected "4eih" [edit=sysop:move=sysop]

2012-04-11T06:44:19Z

Protected "4eih" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:44, 11 April 2012
(No difference)