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2jo8

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Current revision (10:08, 20 December 2023) (edit) (undo)
 
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==Solution structure of C-terminal domain of human mammalian sterile 20-like kinase 1 (MST1)==
==Solution structure of C-terminal domain of human mammalian sterile 20-like kinase 1 (MST1)==
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<StructureSection load='2jo8' size='340' side='right'caption='[[2jo8]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2jo8' size='340' side='right'caption='[[2jo8]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2jo8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JO8 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2jo8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JO8 FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STK4, MST1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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">Solution NMR</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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2jo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jo8 OCA], [https://pdbe.org/2jo8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jo8 RCSB], [https://www.ebi.ac.uk/pdbsum/2jo8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jo8 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=2jo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jo8 OCA], [https://pdbe.org/2jo8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jo8 RCSB], [https://www.ebi.ac.uk/pdbsum/2jo8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jo8 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://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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[https://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>
== 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: Non-specific serine/threonine protein kinase]]
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[[Category: Cheong C]]
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[[Category: Cheong, C]]
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[[Category: Cheong H-K]]
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[[Category: Cheong, H K]]
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[[Category: Guntert P]]
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[[Category: Guntert, P]]
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[[Category: Hwang E]]
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[[Category: Hwang, E]]
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[[Category: Jeon YH]]
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[[Category: Jeon, Y H]]
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[[Category: Lee JO]]
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[[Category: Lee, J O]]
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[[Category: Lim D-S]]
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[[Category: Lim, D S]]
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[[Category: Paakkonen K]]
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[[Category: Paakkonen, K]]
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[[Category: Ryu K-S]]
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[[Category: Ryu, K S]]
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[[Category: C-terminal domain]]
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[[Category: Dimer]]
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[[Category: Human mammalian sterile 20-like kinase 1]]
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[[Category: Protein]]
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[[Category: Transferase]]
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Current revision

Solution structure of C-terminal domain of human mammalian sterile 20-like kinase 1 (MST1)

PDB ID 2jo8

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