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==The crystal structure of human ABL2 in complex with 5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE==
==The crystal structure of human ABL2 in complex with 5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE==
<StructureSection load='3hmi' size='340' side='right' caption='[[3hmi]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
<StructureSection load='3hmi' size='340' side='right'caption='[[3hmi]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3hmi]] 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=3HMI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HMI FirstGlance]. <br>
<table><tr><td colspan='2'>[[3hmi]] 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=3HMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HMI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DKI:5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE'>DKI</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]] 1.65&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gvu|3gvu]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DKI:5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE'>DKI</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABL2 ([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=3hmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmi OCA], [https://pdbe.org/3hmi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hmi RCSB], [https://www.ebi.ac.uk/pdbsum/3hmi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmi 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=3hmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmi OCA], [http://pdbe.org/3hmi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hmi RCSB], [http://www.ebi.ac.uk/pdbsum/3hmi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmi 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>  
== 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/hm/3hmi_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hm/3hmi_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>
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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=3hmi 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=3hmi ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
==See Also==
*[[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: Allerston, C]]
[[Category: Allerston C]]
[[Category: Arrowsmith, C H]]
[[Category: Arrowsmith CH]]
[[Category: Barr, A]]
[[Category: Barr A]]
[[Category: Bountra, C]]
[[Category: Bountra C]]
[[Category: Chaikuad, A]]
[[Category: Chaikuad A]]
[[Category: Delft, F von]]
[[Category: Edwards A]]
[[Category: Edwards, A]]
[[Category: Knapp S]]
[[Category: Knapp, S]]
[[Category: Mahajan P]]
[[Category: Mahajan, P]]
[[Category: Salah E]]
[[Category: Structural genomic]]
[[Category: Savitsky P]]
[[Category: Salah, E]]
[[Category: Shrestha B]]
[[Category: Savitsky, P]]
[[Category: Ugochukwu E]]
[[Category: Shrestha, B]]
[[Category: Weigelt J]]
[[Category: Ugochukwu, E]]
[[Category: Von Delft F]]
[[Category: Weigelt, J]]
[[Category: Abelson murine leukemia viral oncogene]]
[[Category: Abl]]
[[Category: Abl2]]
[[Category: Atp-binding]]
[[Category: Cell adhesion]]
[[Category: Cytoskeleton]]
[[Category: Kinase]]
[[Category: Lipoprotein]]
[[Category: Magnesium]]
[[Category: Manganese]]
[[Category: Metal-binding]]
[[Category: Myristate]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Sgc]]
[[Category: Sh2 domain]]
[[Category: Sh3 domain]]
[[Category: Transferase]]
[[Category: Tyrosine kinase]]
[[Category: Tyrosine-protein kinase]]

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