4k9y - Revision history

OCA at 11:48, 30 November 2022

OCA — Wed, 30 Nov 2022 11:48:11 GMT

←Older revision		Revision as of 11:48, 30 November 2022
Line 1:		Line 1:

	==FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea==		==FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea==
-	<StructureSection load='4k9y' size='340' side='right' caption='[[4k9y]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4k9y' size='340' side='right'caption='[[4k9y]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4k9y]] 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=4K9Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4K9Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4k9y]] 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=4K9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K9Y FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K9Y:1-[4-(6-AMINO-9H-PURIN-9-YL)PHENYL]-3-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA'>K9Y</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K9Y:1-[4-(6-AMINO-9H-PURIN-9-YL)PHENYL]-3-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA'>K9Y</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gu6\|4gu6]], [[4gu9\|4gu9]], [[4k8a\|4k8a]], [[4kab\|4kab]], [[4kao\|4kao]]</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=4k9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9y OCA], [https://pdbe.org/4k9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k9y RCSB], [https://www.ebi.ac.uk/pdbsum/4k9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9y ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTK2, FAK, FAK1 ([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='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=4k9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9y OCA], [~~http~~://pdbe.org/4k9y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4k9y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4k9y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9y ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.<ref>PMID:11980671</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:17431114</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>	+	[https://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN] Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.<ref>PMID:11980671</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:17431114</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.<ref>PMID:10655584</ref> <ref>PMID:11331870</ref> <ref>PMID:11980671</ref> <ref>PMID:15166238</ref> <ref>PMID:15561106</ref> <ref>PMID:15895076</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:16927379</ref> <ref>PMID:17431114</ref> <ref>PMID:18497331</ref> <ref>PMID:18292575</ref> <ref>PMID:18256281</ref> <ref>PMID:18206965</ref> <ref>PMID:19138410</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:20109444</ref> <ref>PMID:21454698</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>	+	[https://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.<ref>PMID:10655584</ref> <ref>PMID:11331870</ref> <ref>PMID:11980671</ref> <ref>PMID:15166238</ref> <ref>PMID:15561106</ref> <ref>PMID:15895076</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:16927379</ref> <ref>PMID:17431114</ref> <ref>PMID:18497331</ref> <ref>PMID:18292575</ref> <ref>PMID:18256281</ref> <ref>PMID:18206965</ref> <ref>PMID:19138410</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:20109444</ref> <ref>PMID:21454698</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Focal adhesion kinase\|Focal adhesion kinase]]	+	*[[Focal adhesion kinase 3D structures\|Focal adhesion 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: Dresing, V]]	+	[[Category: Dresing V]]
-	[[Category: Graedler, U]]	+	[[Category: Graedler U]]
-	[[Category: Heinrich, T]]	+	[[Category: Heinrich T]]
-	[[Category: Lehmann, M]]	+	[[Category: Lehmann M]]
-	[[Category: Musil, D]]	+	[[Category: Musil D]]
-	~~[[Category: Atp binding]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex]]~~	+
-	~~[[Category: Tyrosine protein kinase~~]]	+

OCA at 13:49, 11 August 2016

OCA — Thu, 11 Aug 2016 13:49:27 GMT

←Older revision		Revision as of 13:49, 11 August 2016
Line 1:		Line 1:
		+
	==FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea==		==FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea==
	<StructureSection load='4k9y' size='340' side='right' caption='[[4k9y]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4k9y' size='340' side='right' caption='[[4k9y]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4k9y]] 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=4K9Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K9Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4k9y]] 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=4K9Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K9Y FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K9Y:1-[4-(6-AMINO-9H-PURIN-9-YL)PHENYL]-3-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA'>K9Y</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K9Y:1-[4-(6-AMINO-9H-PURIN-9-YL)PHENYL]-3-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA'>K9Y</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gu6\|4gu6]], [[4gu9\|4gu9]], [[4k8a\|4k8a]], [[4kab\|4kab]], [[4kao\|4kao]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gu6\|4gu6]], [[4gu9\|4gu9]], [[4k8a\|4k8a]], [[4kab\|4kab]], [[4kao\|4kao]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTK2, FAK, FAK1 ([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">PTK2, FAK, FAK1 ([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=4k9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k9y RCSB], [http://www.ebi.ac.uk/pdbsum/4k9y 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=4k9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9y OCA], [http://pdbe.org/4k9y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k9y RCSB], [http://www.ebi.ac.uk/pdbsum/4k9y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k9y ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4k9y" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Dresing, V]]		[[Category: Dresing, V]]

OCA at 14:13, 4 January 2015

OCA — Sun, 04 Jan 2015 14:13:30 GMT

←Older revision		Revision as of 14:13, 4 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4k9y\| PDB=4k9y \| SCENE= }}~~	+	==FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea==
-	===FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea===	+	<StructureSection load='4k9y' size='340' side='right' caption='[[4k9y]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23973211}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4k9y]] 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=4K9Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K9Y FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K9Y:1-[4-(6-AMINO-9H-PURIN-9-YL)PHENYL]-3-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA'>K9Y</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gu6\|4gu6]], [[4gu9\|4gu9]], [[4k8a\|4k8a]], [[4kab\|4kab]], [[4kao\|4kao]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTK2, FAK, FAK1 ([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=4k9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k9y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k9y RCSB], [http://www.ebi.ac.uk/pdbsum/4k9y PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.<ref>PMID:11980671</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:17431114</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>		[[http://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.<ref>PMID:11980671</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:17431114</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.<ref>PMID:10655584</ref> <ref>PMID:11331870</ref> <ref>PMID:11980671</ref> <ref>PMID:15166238</ref> <ref>PMID:15561106</ref> <ref>PMID:15895076</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:16927379</ref> <ref>PMID:17431114</ref> <ref>PMID:18497331</ref> <ref>PMID:18292575</ref> <ref>PMID:18256281</ref> <ref>PMID:18206965</ref> <ref>PMID:19138410</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:20109444</ref> <ref>PMID:21454698</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>		[[http://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.<ref>PMID:10655584</ref> <ref>PMID:11331870</ref> <ref>PMID:11980671</ref> <ref>PMID:15166238</ref> <ref>PMID:15561106</ref> <ref>PMID:15895076</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:16927379</ref> <ref>PMID:17431114</ref> <ref>PMID:18497331</ref> <ref>PMID:18292575</ref> <ref>PMID:18256281</ref> <ref>PMID:18206965</ref> <ref>PMID:19138410</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:20109444</ref> <ref>PMID:21454698</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered by surface plasmon resonance (SPR) screening of our in-house fragment library. Site specific binding of the primary hits was confirmed in a competition setup using a high-affinity ATP-site inhibitor of FAK. Protein crystallography revealed the binding mode of 41 out of 48 selected fragment hits within the ATP-site. Structural comparison of the fragment binding modes with a DFG-out inhibitor of FAK initiated first synthetic follow-up optimization leading to improved binding affinity.

-	~~==About this Structure==~~	+	Fragment-based discovery of focal adhesion kinase inhibitors.,Gradler U, Bomke J, Musil D, Dresing V, Lehmann M, Holzemann G, Greiner H, Esdar C, Krier M, Heinrich T Bioorg Med Chem Lett. 2013 Oct 1;23(19):5401-9. doi: 10.1016/j.bmcl.2013.07.050. , Epub 2013 Jul 31. PMID:23973211<ref>PMID:23973211</ref>
-	~~[[4k9y]] 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=4K9Y OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Focal adhesion kinase\|Focal adhesion kinase]]		*[[Focal adhesion kinase\|Focal adhesion kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:023973211</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: Dresing, V.]]	+	[[Category: Dresing, V]]
-	[[Category: Graedler, U.]]	+	[[Category: Graedler, U]]
-	[[Category: Heinrich, T.]]	+	[[Category: Heinrich, T]]
-	[[Category: Lehmann, M.]]	+	[[Category: Lehmann, M]]
-	[[Category: Musil, D.]]	+	[[Category: Musil, D]]
	[[Category: Atp binding]]		[[Category: Atp binding]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]
	[[Category: Tyrosine protein kinase]]		[[Category: Tyrosine protein kinase]]

OCA at 05:10, 10 October 2013

OCA — Thu, 10 Oct 2013 05:10:55 GMT

←Older revision		Revision as of 05:10, 10 October 2013
Line 11:		Line 11:
	==About this Structure==		==About this Structure==
	[[4k9y]] 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=4K9Y OCA].		[[4k9y]] 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=4K9Y OCA].
		+
		+	==See Also==
		+	*[[Focal adhesion kinase\|Focal adhesion kinase]]

	==Reference==		==Reference==

OCA at 05:24, 12 September 2013

OCA — Thu, 12 Sep 2013 05:24:21 GMT

←Older revision		Revision as of 05:24, 12 September 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4k9y\| PDB=4k9y \| SCENE= }}
		+	===FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea===
		+	{{ABSTRACT_PUBMED_23973211}}

-	~~The entry 4k9y~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.<ref>PMID:11980671</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:17431114</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>

-	~~Authors~~: ~~Musil~~, D., ~~Graedler~~, U., ~~Lehmann~~, M., ~~Heinrich~~, T., ~~Dresing~~, V.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/FAK1_HUMAN FAK1_HUMAN]] Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.<ref>PMID:10655584</ref> <ref>PMID:11331870</ref> <ref>PMID:11980671</ref> <ref>PMID:15166238</ref> <ref>PMID:15561106</ref> <ref>PMID:15895076</ref> <ref>PMID:18006843</ref> <ref>PMID:17395594</ref> <ref>PMID:16927379</ref> <ref>PMID:17431114</ref> <ref>PMID:18497331</ref> <ref>PMID:18292575</ref> <ref>PMID:18256281</ref> <ref>PMID:18206965</ref> <ref>PMID:19138410</ref> <ref>PMID:19147981</ref> <ref>PMID:20495381</ref> <ref>PMID:20109444</ref> <ref>PMID:21454698</ref> <ref>PMID:16919435</ref> <ref>PMID:18677107</ref> <ref>PMID:19224453</ref>

-	~~Description: FOCAL ADHESION KINASE Catalytic domain in complex with~~ 1-[4-(6-~~Amino-purin-9-yl)-phenyl~~]-~~3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea~~	+	==About this Structure==
		+	[[4k9y]] 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=4K9Y OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023973211</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Dresing, V.]]
		+	[[Category: Graedler, U.]]
		+	[[Category: Heinrich, T.]]
		+	[[Category: Lehmann, M.]]
		+	[[Category: Musil, D.]]
		+	[[Category: Atp binding]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]
		+	[[Category: Tyrosine protein kinase]]

OCA at 08:48, 30 June 2013

OCA — Sun, 30 Jun 2013 08:48:18 GMT

←Older revision		Revision as of 08:48, 30 June 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4k9y is ON HOLD	+	The entry 4k9y is ON HOLD until Paper Publication

	Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V.		Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V.

	Description: FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea		Description: FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea

OCA at 07:19, 8 May 2013

OCA — Wed, 08 May 2013 07:19:11 GMT

←Older revision		Revision as of 07:19, 8 May 2013
Line 5:		Line 5:
	Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V.		Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V.

-	Description: FOCAL ADHESION KINASE ~~CATALYTIC DOMAIN IN COMPLEX WITH~~ 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea	+	Description: FOCAL ADHESION KINASE Catalytic domain in complex with 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea

OCA: Protected "4k9y" [edit=sysop:move=sysop]

OCA — Thu, 02 May 2013 07:13:39 GMT

Protected "4k9y" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:13, 2 May 2013

OCA: New page: '''Unreleased structure''' The entry 4k9y is ON HOLD Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V. Description: FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COM...

OCA — Thu, 02 May 2013 07:13:38 GMT

New page: '''Unreleased structure''' The entry 4k9y is ON HOLD Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V. Description: FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COM...

New page

'''Unreleased structure'''

The entry 4k9y is ON HOLD

Authors: Musil, D., Graedler, U., Lehmann, M., Heinrich, T., Dresing, V.

Description: FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH 1-[4-(6-Amino-purin-9-yl)-phenyl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea