4hys - Revision history

OCA at 15:12, 20 September 2023

2023-09-20T15:12:44Z

←Older revision		Revision as of 15:12, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HYS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HYS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</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]] 2.415Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [https://pdbe.org/4hys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [https://www.ebi.ac.uk/pdbsum/4hys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hys 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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [https://pdbe.org/4hys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [https://www.ebi.ac.uk/pdbsum/4hys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hys ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:27, 9 November 2022

2022-11-09T08:27:44Z

←Older revision		Revision as of 08:27, 9 November 2022
Line 1:		Line 1:

	==Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan==		==Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan==
-	<StructureSection load='4hys' size='340' side='right' caption='[[4hys]], [[Resolution\|resolution]] 2.42Å' scene=''>	+	<StructureSection load='4hys' size='340' side='right'caption='[[4hys]], [[Resolution\|resolution]] 2.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4HYS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HYS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hy4\|4hy4]]</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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [https://pdbe.org/4hys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [https://www.ebi.ac.uk/pdbsum/4hys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hys ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, hCG_23734 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [~~http~~://pdbe.org/4hys PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4hys PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4hys 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/~~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: ~~Transferase~~]]	+	[[Category: Large Structures]]
-	[[Category: Janson, C]]	+	[[Category: Janson C]]
-	[[Category: Kuglstatter, A]]	+	[[Category: Kuglstatter A]]
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 19:52, 4 August 2016

2016-08-04T19:52:42Z

←Older revision		Revision as of 19:52, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan==		==Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan==
	<StructureSection load='4hys' size='340' side='right' caption='[[4hys]], [[Resolution\|resolution]] 2.42Å' scene=''>		<StructureSection load='4hys' size='340' side='right' caption='[[4hys]], [[Resolution\|resolution]] 2.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HYS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HYS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hy4\|4hy4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hy4\|4hy4]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, hCG_23734 ([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">MAPK8, hCG_23734 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [http://www.ebi.ac.uk/pdbsum/4hys 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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [http://pdbe.org/4hys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [http://www.ebi.ac.uk/pdbsum/4hys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hys 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 4hys" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Janson, C]]		[[Category: Janson, C]]

OCA at 13:03, 21 December 2014

2014-12-21T13:03:32Z

←Older revision		Revision as of 13:03, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4hys\| PDB=4hys \| SCENE= }}~~	+	==Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan==
-	===Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan===	+	<StructureSection load='4hys' size='340' side='right' caption='[[4hys]], [[Resolution\|resolution]] 2.42Å' scene=''>
-	{~~{ABSTRACT_PUBMED_23352510}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4hys]] 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=4HYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HYS FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BJ:TRANS-4-{[4-(1H-INDAZOL-1-YL)PYRIMIDIN-2-YL]AMINO}CYCLOHEXANOL'>1BJ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hy4\|4hy4]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK8, hCG_23734 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=4hys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hys RCSB], [http://www.ebi.ac.uk/pdbsum/4hys 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/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 ==
		+	A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation.

-	~~==Function==~~	+	Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead.,Palmer WS, Alam M, Arzeno HB, Chang KC, Dunn JP, Goldstein DM, Gong L, Goyal B, Hermann JC, Hogg JH, Hsieh G, Jahangir A, Janson C, Jin S, Ursula Kammlott R, Kuglstatter A, Lukacs C, Michoud C, Niu L, Reuter DC, Shao A, Silva T, Trejo-Martin TA, Stein K, Tan YC, Tivitmahaisoon P, Tran P, Wagner P, Weller P, Wu SY Bioorg Med Chem Lett. 2013 Mar 1;23(5):1486-92. doi: 10.1016/j.bmcl.2012.12.047. , Epub 2012 Dec 22. PMID:23352510<ref>PMID:23352510</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>
-	~~[[4hys]] 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=4HYS OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023352510</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]
-	[[Category: Janson, C.]]	+	[[Category: Janson, C]]
-	[[Category: Kuglstatter, A.]]	+	[[Category: Kuglstatter, A]]
	[[Category: Kinase inhibitor]]		[[Category: Kinase inhibitor]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 09:39, 30 October 2013

2013-10-30T09:39:10Z

←Older revision		Revision as of 09:39, 30 October 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4hys\| PDB=4hys \| SCENE= }}
		+	===Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan===
		+	{{ABSTRACT_PUBMED_23352510}}

-	~~The~~ entry ~~4hys~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Kuglstatter, A~~., ~~Janson~~, C.	+	==Function==
		+	[[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.

-	~~Description: Crystal~~ structure ~~of JNK1 in complex~~ with ~~JIP1 peptide and 4~~-~~(4-Indazol~~-~~1-yl-pyrimidin-2-ylamino)-cyclohexan~~	+	==About this Structure==
		+	[[4hys]] 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=4HYS OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023352510</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Transferase]]
		+	[[Category: Janson, C.]]
		+	[[Category: Kuglstatter, A.]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 20:46, 12 December 2012

2012-12-12T20:46:12Z

←Older revision		Revision as of 20:46, 12 December 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Kuglstatter, A., Janson, C.		Authors: Kuglstatter, A., Janson, C.

	Description: Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan		Description: Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan

OCA at 10:30, 5 December 2012

2012-12-05T10:30:30Z

←Older revision		Revision as of 10:30, 5 December 2012
Line 5:		Line 5:
	Authors: Kuglstatter, A., Janson, C.		Authors: Kuglstatter, A., Janson, C.

-	Description: ~~CRYSTAL STRUCTURE OF~~ JNK1 ~~IN COMPLEX WITH~~ JIP1 ~~PEPTIDE AND~~ 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan	+	Description: Crystal structure of JNK1 in complex with JIP1 peptide and 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan

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

2012-11-21T09:10:18Z

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

←Older revision

Revision as of 09:10, 21 November 2012

OCA: New page: '''Unreleased structure''' The entry 4hys is ON HOLD Authors: Kuglstatter, A., Janson, C. Description: CRYSTAL STRUCTURE OF JNK1 IN COMPLEX WITH JIP1 PEPTIDE AND 4-(4-Indazol-1-yl-pyri...

2012-11-21T09:10:16Z

New page: '''Unreleased structure''' The entry 4hys is ON HOLD Authors: Kuglstatter, A., Janson, C. Description: CRYSTAL STRUCTURE OF JNK1 IN COMPLEX WITH JIP1 PEPTIDE AND 4-(4-Indazol-1-yl-pyri...

New page

'''Unreleased structure'''

The entry 4hys is ON HOLD

Authors: Kuglstatter, A., Janson, C.

Description: CRYSTAL STRUCTURE OF JNK1 IN COMPLEX WITH JIP1 PEPTIDE AND 4-(4-Indazol-1-yl-pyrimidin-2-ylamino)-cyclohexan