Version 5.4
Bos taurus Protein: GRK5
Summary
InnateDB Protein IDBP-692626.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol GRK5
Protein Name G protein-coupled receptor kinase 5
Synonyms GPRK5;
Species Bos taurus
Ensembl Protein ENSBTAP00000010492
InnateDB Gene IDBG-640359 (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 (Beta-2 adrenergic receptor), 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) (By similarity). {ECO:0000250}.
Subcellular Localization Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. 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 (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Highest levels in lung, heart, retina, lingual epithelium. Very little in brain, liver, kidney. {ECO:0000269PubMed:8120045}.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 158 interaction(s) predicted by orthology.
Experimentally validated
Total 1 [view]
Protein-Protein 1 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 158 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004703 G-protein coupled receptor kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008289 lipid binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
Biological Process
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007217 tachykinin receptor signaling pathway
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway
GO:0016055 Wnt signaling pathway
GO:0016310 phosphorylation
GO:0038032 termination of G-protein coupled receptor signaling pathway
GO:0043066 negative regulation of apoptotic process
GO:0046777 protein autophosphorylation
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0016020 membrane
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
PFAM PF00615
PF00069
PF07714
PRINTS PR00717
PR01301
PR00109
PIRSF
SMART SM00133
SM00220
SM00315
SM00219
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P43249
PhosphoSite PhosphoSite-P43249
TrEMBL
UniProt Splice Variant
Entrez Gene 281801
UniGene Bt.4263
RefSeq NP_776756
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL U01206
GenPept AAA17561

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca