View source for 9brm


==Crystal Structure of Human G Protein-Coupled Receptor Kinase 5 in Complex with GRL077-22==
<StructureSection load='9brm' size='340' side='right'caption='[[9brm]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9brm]] 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=9BRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BRM 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]] 2.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ARC:(3~{Z})-3-[[3,5-dimethyl-4-[[(2~{S})-2-(oxan-4-yl)-2-oxidanyl-ethyl]carbamoyl]-1~{H}-pyrrol-2-yl]methylidene]-2-oxidanylidene-~{N}-[(1~{R})-1-phenylethyl]-7~{H}-indole-5-carboxamide'>A1ARC</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=9brm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9brm OCA], [https://pdbe.org/9brm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9brm RCSB], [https://www.ebi.ac.uk/pdbsum/9brm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9brm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRK5_HUMAN GRK5_HUMAN] Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro).<ref>PMID:19661922</ref> <ref>PMID:19801552</ref> <ref>PMID:20038610</ref> <ref>PMID:20124405</ref> <ref>PMID:21728385</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen Y]]
[[Category: Tesmer JJG]]