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| ==Crystal structure of Mst1 kinase== | | ==Crystal structure of Mst1 kinase== |
| <StructureSection load='3com' size='340' side='right' caption='[[3com]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3com' size='340' side='right'caption='[[3com]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3com]] 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=3COM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3COM FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3COM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3COM FirstGlance]. <br> |
| </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | | </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=3com FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3com OCA], [https://pdbe.org/3com PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3com RCSB], [https://www.ebi.ac.uk/pdbsum/3com PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3com ProSAT], [https://www.topsan.org/Proteins/NYSGXRC/3com TOPSAN]</span></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STK4, MST1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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| <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=3com FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3com OCA], [http://pdbe.org/3com PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3com RCSB], [http://www.ebi.ac.uk/pdbsum/3com PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3com ProSAT], [http://www.topsan.org/Proteins/NYSGXRC/3com TOPSAN]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[http://www.uniprot.org/uniprot/STK4_HUMAN STK4_HUMAN]] Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.<ref>PMID:8816758</ref> <ref>PMID:8702870</ref> <ref>PMID:11278283</ref> <ref>PMID:11517310</ref> <ref>PMID:12757711</ref> <ref>PMID:15109305</ref> <ref>PMID:16510573</ref> <ref>PMID:16751106</ref> <ref>PMID:16930133</ref> <ref>PMID:17932490</ref> <ref>PMID:18328708</ref> <ref>PMID:18986304</ref> <ref>PMID:19525978</ref> <ref>PMID:21245099</ref> <ref>PMID:21512132</ref> <ref>PMID:21212262</ref>
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| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| ==See Also== | | ==See Also== |
| *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Large Structures]] |
| [[Category: Non-specific serine/threonine protein kinase]]
| | [[Category: Atwell S]] |
| [[Category: Atwell, S]] | | [[Category: Burley SK]] |
| [[Category: Burley, S K]] | | [[Category: Dickey M]] |
| [[Category: Dickey, M]] | | [[Category: Leon B]] |
| [[Category: Leon, B]] | | [[Category: Sauder JM]] |
| [[Category: Structural genomic]]
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| [[Category: Sauder, J M]] | |
| [[Category: Alternative splicing]]
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| [[Category: Apoptosis]]
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| [[Category: Atp-binding]]
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| [[Category: Coiled coil]]
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| [[Category: Cytoplasm]]
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| [[Category: Kinase]]
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| [[Category: Magnesium]]
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| [[Category: Metal-binding]]
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| [[Category: Mst1]]
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| [[Category: Nucleotide-binding]]
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| [[Category: Nucleus]]
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| [[Category: NYSGXRC, New York SGX Research Center for Structural Genomics]]
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| [[Category: Phosphoprotein]]
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| [[Category: Polymorphism]]
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| [[Category: PSI, Protein structure initiative]]
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| [[Category: Serine/threonine-protein kinase 4]]
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| [[Category: Ste20-like kinase]]
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| [[Category: Transferase]]
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