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<StructureSection load='3vug' size='340' side='right'caption='[[3vug]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
<StructureSection load='3vug' size='340' side='right'caption='[[3vug]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3vug]] 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=3VUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VUG FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vug]] 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=3VUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VUG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3.24&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vud|3vud]], [[3vuh|3vuh]], [[3vui|3vui]], [[3vuk|3vuk]], [[3vul|3vul]], [[3vum|3vum]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vug OCA], [https://pdbe.org/3vug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vug RCSB], [https://www.ebi.ac.uk/pdbsum/3vug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vug 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=3vug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vug OCA], [https://pdbe.org/3vug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vug RCSB], [https://www.ebi.ac.uk/pdbsum/3vug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vug ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/JIP1_HUMAN JIP1_HUMAN]] Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://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 ==
[[https://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;">
== Publication Abstract from PubMed ==
Intracellular proteins can have free cysteines that may contribute to their structure, function, and stability; however, free cysteines can lead to chemical instabilities in solution because of oxidation-driven aggregation. The MAP kinase, c-Jun N-terminal kinase 1 (JNK1), possesses seven free cysteines and is an important drug target for autoimmune diseases, cancers, and apoptosis-related diseases. To characterize the role of cysteine residues in the structure, function, and stability of JNK1, we prepared and evaluated wild-type JNK1 and seven cysteine-deficient JNK1 proteins. The nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments showed that the chemical stability of JNK1 increased as the number of cysteines decreased. The contribution of each cysteine residue to biological function and thermal stability was highly susceptible to the environment surrounding the particular cysteine mutation. The mutations of solvent-exposed cysteine to serine did not influence biological function and increased the thermal stability. The mutation of the accessible cysteine involved in the hydrophobic pocket did not affect biological function, although a moderate thermal destabilization was observed. Cysteines in the loosely assembled hydrophobic environment moderately contributed to thermal stability, and the mutations of these cysteines had a negligible effect on enzyme activity. The other cysteines are involved in the tightly filled hydrophobic core, and mutation of these residues was found to correlate with thermal stability and enzyme activity. These findings about the role of cysteine residues should allow us to obtain a stable JNK1 and thus promote the discovery of potent JNK1 inhibitors.
 
Seven cysteine-deficient mutants depict the interplay between thermal and chemical stabilities of individual cysteine residues in mitogen-activated protein kinase c-Jun N-terminal kinase 1.,Nakaniwa T, Fukada H, Inoue T, Gouda M, Nakai R, Kirii Y, Adachi M, Tamada T, Segawa S, Kuroki R, Tada T, Kinoshita T Biochemistry. 2012 Oct 23;51(42):8410-21. doi: 10.1021/bi300918w. Epub 2012 Oct, 11. PMID:23020677<ref>PMID:23020677</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vug" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Mitogen-activated protein kinase]]
[[Category: Inoue T]]
[[Category: Inoue, T]]
[[Category: Kinoshita T]]
[[Category: Kinoshita, T]]
[[Category: Nakaniwa T]]
[[Category: Nakaniwa, T]]
[[Category: Atp binding]]
[[Category: Map kinase]]
[[Category: Phosphorylation]]
[[Category: Transcription]]
[[Category: Transferase-transferase inhibitor complex]]

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