ARRB1: regulates G-protein coupled receptors (GPCR) signaling by mediating both receptor desensitization and resensitization processes. Binds to GRK-phosphorylated receptor and sterically preclude its coupling to the cognate G- protein; the binding appears to require receptor determinants exposed only in the active receptor conformation. Targets many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins). Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Also involved in regulation of receptors other than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6). Involved in IL8-mediated granule release in neutrophils. Interacts with phosphorylated ADRB2 and CHRM2. Interacts with SRC (via the SH3 domain and the protein kinase domain); the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with RAF1, CHUK, IKBKB and Nik. Interacts with DVL1 and DVL2; the interaction is enhanced by DVL phosphorylation. Interacts with IGF1R. Belongs to the arrestin family. 2 isoforms of the human protein are produced by alternative splicing.
Protein type: Adaptor/scaffold
Chromosomal Location of Human Ortholog: 11q13
Cellular Component: cytoplasmic vesicle membrane; lysosomal membrane; coated pit; pseudopodium; cytosol; nucleoplasm; Golgi membrane; cytoplasm; plasma membrane; heterotrimeric G-protein complex; cytoplasmic vesicle; nucleus; chromatin
Molecular Function: angiotensin receptor binding; enzyme inhibitor activity; insulin-like growth factor receptor binding; protein binding; histone acetyltransferase activity; mitogen-activated protein kinase kinase binding; ubiquitin protein ligase binding; caspase inhibitor activity; transcription factor binding; GTPase activator activity
Biological Process: transcription from RNA polymerase II promoter; platelet activation; proteasomal ubiquitin-dependent protein catabolic process; Notch signaling pathway; positive regulation of protein binding; positive regulation of receptor internalization; positive regulation of Rho protein signal transduction; protein ubiquitination; negative regulation of caspase activity; positive regulation of peptidyl-serine phosphorylation; protein transport; G-protein coupled receptor internalization; inhibition of NF-kappaB transcription factor; negative regulation of interleukin-8 production; phototransduction; stress fiber formation; negative regulation of interleukin-6 production; negative regulation of protein ubiquitination; positive regulation of transcription from RNA polymerase II promoter; positive regulation of histone acetylation; positive regulation of protein amino acid phosphorylation; post-Golgi vesicle-mediated transport; blood coagulation; positive regulation of GTPase activity
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