InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Grk5

Summary

InnateDB Protein

IDBP-181928.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Grk5

Protein Name

G protein-coupled receptor kinase 5

Synonyms

Gprk5;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000003313

InnateDB Gene

IDBG-181926 (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:10624964, ECO:0000269PubMed:14565944, ECO:0000269PubMed:18711143, ECO:0000269PubMed:19478075}.

Subcellular Localization

Cytoplasm {ECO:0000250}. 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
They are also associated with 162 interaction(s) predicted by orthology.

Experimentally validated
Total	2 [view]
Protein-Protein	2 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	162 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007217	tachykinin receptor signaling pathway
GO:0016055	Wnt signaling pathway
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

Protein Structure and Domains

PDB ID

MGI:109161

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