ARRB1 cDNA Clone – Arrestin, Beta 1 (Human)

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]

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: chromatin; cytoplasm; cytoplasmic vesicle; cytoplasmic vesicle membrane; cytosol; Golgi membrane; heterotrimeric G-protein complex; lysosomal membrane; nucleoplasm; nucleus; plasma membrane

Molecular Function: angiotensin receptor binding; enzyme inhibitor activity; GTPase activator activity; histone acetyltransferase activity; insulin-like growth factor receptor binding; protein binding; transcription factor binding; ubiquitin protein ligase binding

Biological Process: G-protein coupled receptor internalization; inhibition of NF-kappaB transcription factor; negative regulation of interleukin-6 production; negative regulation of interleukin-8 production; negative regulation of protein ubiquitination; platelet activation; positive regulation of histone acetylation; positive regulation of protein amino acid phosphorylation; positive regulation of receptor internalization; positive regulation of Rho protein signal transduction; positive regulation of transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; protein ubiquitination; stress fiber formation; transcription from RNA polymerase II promoter