GRK5

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).

GRK5 Related Areas

Cardiovascular>>Blood Pressure Regulation>>GRK5

Enzyme>>Protein Kinase>>Intracellular Kinase>>G Protein-Coupled Receptor Kinase (GRK)>>GRK5

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>G Protein-Coupled Receptor Kinase (GRK)>>GRK5

GRK5 Alternative Names

GRK5, FLJ39780, GPRK5 [Homo sapiens]

Grk5, Gprk5 [Mus musculus]

Summaries for GRK5

Entrez Gene summary for GRK5:

This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs).

OMIM - description for GRK5:

G protein-coupled receptor (GPCR) kinases (GRKs), such as GRK5, are important regulators of GPCR function and mediate receptor desensitization, internalization, and signaling. Several non-GPCR proteins also serve as GRK substrates, and GRKs have been shown to have kinase-independent functions in receptor and effector regulation

Wikipedia summary for GRK5:

G protein-coupled receptor kinase 5 is an enzyme that in humans is encoded by the GRK5 gene.[1][2] This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs)

Human GRK5 Protein General Information

 

• Protein names: Recommended name: G protein-coupled receptor kinase 5
• Sequence length: 590 AA.
• Sequence similarities: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 protein kinase domain. Contains 1 RGS domain.
• Polymorphism: Variant Leu-41 variant is rare in European-Americans individuals but common in African-Americans individuals (40% of the African-American individuals studied carry at least one allele). Variant leu-41 is associated with decreased mortality in African-Americans with heart failure or cardiac ischemia.
• Subunit structure: Interacts with ST13 (via the C-terminus 303-319 AA). Interacts with TP53/p53. Interacts with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT (serotonin). Interacts with HDAC5
• Subcellular location: 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 Ca2+/calmodulin-dependent fashion.
• Tissue specificity: Highest levels in heart, placenta, lung > skeletal muscle > brain, liver, pancreas > kidney.
• Catalytic activity: ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.

General information above from UniProt

Function for GRK5 Protein

UniProtKB:

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).

Genatlas:

• GRK mediates phosphatidylinositol 4,5-biphosphate (PIP2) dependent phosphorylation of beta adrenergic receptor 1
• inhibition of thrombin-activated phosphoinositide hydrolysis in endothelial cells
• nuclear HDAC kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on GPCRs
• GRK5/6 is a novel kinases for the single transmembrane receptor LRP6 during Wnt signaling