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3e7o

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Current revision (12:59, 30 August 2023) (edit) (undo)
 
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<StructureSection load='3e7o' size='340' side='right'caption='[[3e7o]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
<StructureSection load='3e7o' size='340' side='right'caption='[[3e7o]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3e7o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3e7o]] 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=3E7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7O FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=35F:N-{3-[5-(1H-1,2,4-TRIAZOL-3-YL)-1H-INDAZOL-3-YL]PHENYL}FURAN-2-CARBOXAMIDE'>35F</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK9, JNK2, PRKM9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=35F:N-{3-[5-(1H-1,2,4-TRIAZOL-3-YL)-1H-INDAZOL-3-YL]PHENYL}FURAN-2-CARBOXAMIDE'>35F</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7o OCA], [https://pdbe.org/3e7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7o RCSB], [https://www.ebi.ac.uk/pdbsum/3e7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7o 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=3e7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7o OCA], [https://pdbe.org/3e7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7o RCSB], [https://www.ebi.ac.uk/pdbsum/3e7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7o ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/MK09_HUMAN MK09_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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:10376527</ref> <ref>PMID:15805466</ref> <ref>PMID:17525747</ref> <ref>PMID:19675674</ref> <ref>PMID:20595622</ref> <ref>PMID:21364637</ref> MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.<ref>PMID:10376527</ref> <ref>PMID:15805466</ref> <ref>PMID:17525747</ref> <ref>PMID:19675674</ref> <ref>PMID:20595622</ref> <ref>PMID:21364637</ref>
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[https://www.uniprot.org/uniprot/MK09_HUMAN MK09_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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:10376527</ref> <ref>PMID:15805466</ref> <ref>PMID:17525747</ref> <ref>PMID:19675674</ref> <ref>PMID:20595622</ref> <ref>PMID:21364637</ref> MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.<ref>PMID:10376527</ref> <ref>PMID:15805466</ref> <ref>PMID:17525747</ref> <ref>PMID:19675674</ref> <ref>PMID:20595622</ref> <ref>PMID:21364637</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Mitogen-activated protein kinase]]
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[[Category: Kuglstatter A]]
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[[Category: Kuglstatter, A]]
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[[Category: Villasenor AG]]
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[[Category: Villasenor, A G]]
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[[Category: Activation loop]]
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[[Category: Atp-binding]]
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[[Category: Indazole inhibitor]]
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[[Category: Kinase]]
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[[Category: Map kinase insert]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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Current revision

Crystal Structure of JNK2

PDB ID 3e7o

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