View source for 8xey


==The Crystal Structure of C-terminal kinase domain of RSK2 from Biortus==
<StructureSection load='8xey' size='340' side='right'caption='[[8xey]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8xey]] is a 1 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=8XEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XEY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=8xey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xey OCA], [https://pdbe.org/8xey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xey RCSB], [https://www.ebi.ac.uk/pdbsum/8xey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xey ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KS6A3_HUMAN KS6A3_HUMAN] Coffin-Lowry syndrome;X-linked nonsyndromic intellectual deficit. Defects in RPS6KA3 are the cause of Coffin-Lowry syndrome (CLS) [MIM:[https://omim.org/entry/303600 303600]. A X-linked mental retardation associated with facial and digital dysmorphisms, progressive skeletal malformations, growth retardation, hearing deficit and paroxysmal movement disorders.<ref>PMID:8955270</ref> <ref>PMID:9837815</ref> <ref>PMID:10094187</ref> <ref>PMID:10528858</ref> <ref>PMID:14986828</ref> <ref>PMID:15214012</ref>   Defects in RPS6KA3 are the cause of mental retardation X-linked type 19 (MRX19) [MIM:[https://omim.org/entry/300844 300844]. MRX19 is a non-syndromic form of mild to moderate mental retardation. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. In contrast to syndromic or specific X-linked mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation.<ref>PMID:10319851</ref> <ref>PMID:17100996</ref> 
== Function ==
[https://www.uniprot.org/uniprot/KS6A3_HUMAN KS6A3_HUMAN] Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1.<ref>PMID:8250835</ref> <ref>PMID:9770464</ref> <ref>PMID:10436156</ref> <ref>PMID:16213824</ref> <ref>PMID:16223362</ref> <ref>PMID:17360704</ref> <ref>PMID:18722121</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng W]]
[[Category: Lv Z]]
[[Category: Meng Q]]
[[Category: Wang F]]
[[Category: Zhang B]]