Homo sapiens Protein: GRK5 | |||||||||||||||||||||||
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Summary | |||||||||||||||||||||||
InnateDB Protein | IDBP-244779.6 | ||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||
Gene Symbol | GRK5 | ||||||||||||||||||||||
Protein Name | G protein-coupled receptor kinase 5 | ||||||||||||||||||||||
Synonyms | GPRK5; | ||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||
Ensembl Protein | ENSP00000376609 | ||||||||||||||||||||||
InnateDB Gene | IDBG-91131 (GRK5) | ||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||
Function | 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). {ECO:0000269PubMed:19661922, ECO:0000269PubMed:19801552, ECO:0000269PubMed:20038610, ECO:0000269PubMed:20124405, ECO:0000269PubMed:21728385}. | ||||||||||||||||||||||
Subcellular Localization | Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note=Predominantly localized at the plasma membrane; targeted to the cell surface through the interaction with phospholipids. Nucleus localization is regulated in a GPCR and Ca(2+)/calmodulin-dependent fashion. | ||||||||||||||||||||||
Disease Associations | |||||||||||||||||||||||
Tissue Specificity | Highest levels in heart, placenta, lung > skeletal muscle > brain, liver, pancreas > kidney. {ECO:0000269PubMed:7685906}. | ||||||||||||||||||||||
Comments | |||||||||||||||||||||||
Interactions | |||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 193 experimentally validated interaction(s) in this database.
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Gene Ontology | |||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||
InterPro |
IPR000239
GPCR kinase IPR000342 Regulator of G protein signalling domain IPR000719 Protein kinase domain IPR000961 AGC-kinase, C-terminal IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR011009 Protein kinase-like domain IPR016137 Regulator of G protein signalling superfamily IPR020635 Tyrosine-protein kinase, catalytic domain |
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PFAM |
PF00615
PF00069 PF07714 |
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PRINTS |
PR00717
PR01301 PR00109 |
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PIRSF | |||||||||||||||||||||||
SMART |
SM00133
SM00220 SM00315 SM00219 |
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TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | P34947 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-P34947 | ||||||||||||||||||||||
TrEMBL | Q24JT8 | ||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 2869 | ||||||||||||||||||||||
UniGene | Hs.524625 | ||||||||||||||||||||||
RefSeq | NP_005299 | ||||||||||||||||||||||
HUGO | HGNC:4544 | ||||||||||||||||||||||
OMIM | 600870 | ||||||||||||||||||||||
CCDS | CCDS7612 | ||||||||||||||||||||||
HPRD | 02926 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AL355273 AL355861 AL583824 BC064506 BC114448 CH471066 L15388 | ||||||||||||||||||||||
GenPept | AAA58620 AAH64506 AAI14449 CAI15804 CAI16487 CAI16759 EAW49394 EAW49395 | ||||||||||||||||||||||