4e73 - Revision history

OCA at 14:54, 14 March 2024

OCA — Thu, 14 Mar 2024 14:54:04 GMT

←Older revision		Revision as of 14:54, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E73 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E73 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</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]] 2.27Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [https://pdbe.org/4e73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [https://www.ebi.ac.uk/pdbsum/4e73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e73 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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [https://pdbe.org/4e73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [https://www.ebi.ac.uk/pdbsum/4e73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e73 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref>	+	[https://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl-1, 4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified as a novel, druglike and selective quinolone pan JNK inhibitor. In this communication, some of the structure-activity relationship of the azaquinolone analogues leading to 4 is discussed. The focus is on how changes at the amide functionality affected the biochemical potency, cellular potency, metabolic properties, and solubility of this class of JNK inhibitors. Optimization of these properties led to the identification of the adamantyl analogue, 4. 4 achieved proof of mechanism in both rat and mouse TNF-alpha challenge models.	+
-		+
-	Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor.,Haynes NE, Scott NR, Chen LC, Janson CA, Li JK, Lukacs CM, Railkar A, Tozzo E, Whittard T, Brown NF, Cheung AW ACS Med Chem Lett. 2012 Aug 8;3(9):764-8. doi: 10.1021/ml300175c. eCollection, 2012 Sep 13. PMID:24900545<ref>PMID:24900545</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4e73" style="background-color:#fffaf0;"></div~~>	+

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

OCA at 06:54, 28 September 2022

OCA — Wed, 28 Sep 2022 06:54:38 GMT

←Older revision		Revision as of 06:54, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor==		==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor==
-	<StructureSection load='4e73' size='340' side='right' caption='[[4e73]], [[Resolution\|resolution]] 2.27Å' scene=''>	+	<StructureSection load='4e73' size='340' side='right'caption='[[4e73]], [[Resolution\|resolution]] 2.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E73 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E73 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ukh\|1ukh]]</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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [https://pdbe.org/4e73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [https://www.ebi.ac.uk/pdbsum/4e73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e73 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, JNK1, PRKM8, SAPK1, SAPK1C ([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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [~~http~~://pdbe.org/4e73 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e73 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e73 ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> [[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response.	+	[[https://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 20:

	==See Also==		==See Also==
-	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]	+	*[[Mitogen-activated protein kinase 3D structures\|Mitogen-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Mitogen-activated protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Janson~~, C A~~]]	+	[[Category: Janson CA]]
-	[[Category: Lukacs~~, C M]]~~	+	[[Category: Lukacs CM]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 14:00, 11 August 2016

OCA — Thu, 11 Aug 2016 14:00:49 GMT

←Older revision		Revision as of 14:00, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor==		==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor==
	<StructureSection load='4e73' size='340' side='right' caption='[[4e73]], [[Resolution\|resolution]] 2.27Å' scene=''>		<StructureSection load='4e73' size='340' side='right' caption='[[4e73]], [[Resolution\|resolution]] 2.27Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, JNK1, PRKM8, SAPK1, SAPK1C ([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">MAPK8, JNK1, PRKM8, SAPK1, SAPK1C ([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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [http://www.ebi.ac.uk/pdbsum/4e73 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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [http://pdbe.org/4e73 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [http://www.ebi.ac.uk/pdbsum/4e73 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e73 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 4e73" style="background-color:#fffaf0;"></div>

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

OCA at 11:48, 20 January 2015

OCA — Tue, 20 Jan 2015 11:48:15 GMT

←Older revision		Revision as of 11:48, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E73 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E73 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ukh\|1ukh]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ukh\|1ukh]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, JNK1, PRKM8, SAPK1, SAPK1C ([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">MAPK8, JNK1, PRKM8, SAPK1, SAPK1C ([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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [http://www.ebi.ac.uk/pdbsum/4e73 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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [http://www.ebi.ac.uk/pdbsum/4e73 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref>		[[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref>
Line 30:		Line 30:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
-	[[Category: Janson, C A.]]	+	[[Category: Janson, C A]]
-	[[Category: Lukacs, C M.]]	+	[[Category: Lukacs, C M]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:06, 24 September 2014

OCA — Wed, 24 Sep 2014 07:06:04 GMT

←Older revision		Revision as of 07:06, 24 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4e73\| PDB=4e73 \| SCENE= }}~~	+	==Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor==
-	===Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor===	+	<StructureSection load='4e73' size='340' side='right' caption='[[4e73]], [[Resolution\|resolution]] 2.27Å' scene=''>
-		+	== Structural highlights ==
-	==Disease==	+	<table><tr><td colspan='2'>[[4e73]] is a 2 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=4E73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E73 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NR:METHYL+3-(4-{[(1R,2S,3S,5S,7S)-5-AMINOTRICYCLO[3.3.1.1~3,7~]DEC-2-YL]CARBAMOYL}BENZYL)-4-OXO-1-PHENYL-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-2-CARBOXYLATE'>0NR</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ukh\|1ukh]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, JNK1, PRKM8, SAPK1, SAPK1C ([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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=4e73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e73 RCSB], [http://www.ebi.ac.uk/pdbsum/4e73 PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref>		[[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> [[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl-1, 4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified as a novel, druglike and selective quinolone pan JNK inhibitor. In this communication, some of the structure-activity relationship of the azaquinolone analogues leading to 4 is discussed. The focus is on how changes at the amide functionality affected the biochemical potency, cellular potency, metabolic properties, and solubility of this class of JNK inhibitors. Optimization of these properties led to the identification of the adamantyl analogue, 4. 4 achieved proof of mechanism in both rat and mouse TNF-alpha challenge models.

-	~~==Function==~~	+	Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor.,Haynes NE, Scott NR, Chen LC, Janson CA, Li JK, Lukacs CM, Railkar A, Tozzo E, Whittard T, Brown NF, Cheung AW ACS Med Chem Lett. 2012 Aug 8;3(9):764-8. doi: 10.1021/ml300175c. eCollection, 2012 Sep 13. PMID:24900545<ref>PMID:24900545</ref>
-	~~[[http://www~~.~~uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation~~, ~~differentiation~~, ~~migration~~, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, ~~two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn~~, ~~MAPK8/JNK1 phosphorylates a number of transcription factors~~, ~~primarily components of AP-1 such as JUN~~, ~~JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1~~, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, ~~MAPK8 and MAPK9 are required for polarized differentiation of~~ T~~-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation~~, ~~BCL2 dissociation from BECN1~~, ~~and thus activation of autophagy~~. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (~~HSF4~~)~~, the deacetylase SIRT1, ELK1, or the E3 ligase ITCH~~.~~<ref>PMID~~:~~16581800<~~/ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. ~~However~~, ~~there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms~~.~~<ref>~~PMID:~~16581800</ref>~~ <ref>PMID:~~17296730~~</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> [[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4e73]] is~~ a ~~2 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=4E73 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	<references ~~group="xtra"~~/><~~references~~/>	+	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
-	[[Category: ~~Homo sapiens~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Janson, C A.]]		[[Category: Janson, C A.]]

OCA at 16:17, 19 June 2013

OCA — Wed, 19 Jun 2013 16:17:27 GMT

←Older revision		Revision as of 16:17, 19 June 2013
Line 1:		Line 1:
-	~~WITHDRAWN: The~~ PDB entry 4E73 ~~was withdrawn~~.	+	{{STRUCTURE_4e73\| PDB=4e73 \| SCENE= }}
		+	===Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor===
		+
		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:10700186</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/MK08_HUMAN MK08_HUMAN]] Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.<ref>PMID:16581800</ref> <ref>PMID:17296730</ref> <ref>PMID:18307971</ref> <ref>PMID:18570871</ref> <ref>PMID:20027304</ref> <ref>PMID:21364637</ref> <ref>PMID:21095239</ref> <ref>PMID:21856198</ref> [[http://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response.
		+
		+	==About this Structure==
		+	[[4e73]] is a 2 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=4E73 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Mitogen-activated protein kinase]]
		+	[[Category: Janson, C A.]]
		+	[[Category: Lukacs, C M.]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 01:19, 4 April 2013

OCA — Thu, 04 Apr 2013 01:19:05 GMT

←Older revision		Revision as of 01:19, 4 April 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	WITHDRAWN: The PDB entry 4E73 was withdrawn.
-		+
-	The entry ~~4e73 is ON HOLD until Paper Publication~~	+
-		+
-	~~Authors: Lukacs, C~~.~~M., Janson, C.A.~~	+
-		+
-	~~Description: Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor~~	+

OCA at 06:39, 11 April 2012

OCA — Wed, 11 Apr 2012 06:39:14 GMT

←Older revision		Revision as of 06:39, 11 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4e73 is ON HOLD	+	The entry 4e73 is ON HOLD until Paper Publication

	Authors: Lukacs, C.M., Janson, C.A.		Authors: Lukacs, C.M., Janson, C.A.

	Description: Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor		Description: Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor

OCA: Protected "4e73" [edit=sysop:move=sysop]

OCA — Wed, 28 Mar 2012 07:22:57 GMT

Protected "4e73" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:22, 28 March 2012

OCA: New page: '''Unreleased structure''' The entry 4e73 is ON HOLD Authors: Lukacs, C.M., Janson, C.A. Description: Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor

OCA — Wed, 28 Mar 2012 07:22:57 GMT

New page: '''Unreleased structure''' The entry 4e73 is ON HOLD Authors: Lukacs, C.M., Janson, C.A. Description: Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor

New page

'''Unreleased structure'''

The entry 4e73 is ON HOLD

Authors: Lukacs, C.M., Janson, C.A.

Description: Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor