ARRB1 iso2 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. Note: This description may include information from UniProtKB..
Protein type: Adaptor/scaffold
Chromosomal Location of Human Ortholog: 11q13.4
Cellular Component:  basolateral plasma membrane; chromatin; clathrin-coated pit; cytoplasm; cytoplasmic vesicle; cytoplasmic vesicle membrane; cytosol; dendritic spine; endosome; Golgi membrane; lysosomal membrane; nuclear body; nucleoplasm; nucleus; plasma membrane; postsynaptic density; postsynaptic membrane; pseudopodium
Molecular Function:  alpha-1A adrenergic receptor binding; alpha-1B adrenergic receptor binding; angiotensin receptor binding; AP-2 adaptor complex binding; arrestin family protein binding; clathrin adaptor activity; cysteine-type endopeptidase inhibitor activity involved in apoptotic process; enzyme inhibitor activity; estrogen receptor binding; follicle-stimulating hormone receptor binding; GTPase activator activity; insulin-like growth factor receptor binding; ion channel binding; mitogen-activated protein kinase kinase binding; protein binding; protein phosphorylated amino acid binding; transcription factor binding; transcription regulatory region DNA binding; ubiquitin protein ligase binding; V2 vasopressin receptor binding
Biological Process:  activation of MAPK activity; apoptotic process; follicle-stimulating hormone signaling pathway; G protein-coupled receptor internalization; G protein-coupled receptor signaling pathway; histone acetylation; membrane organization; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of ERK1 and ERK2 cascade; negative regulation of GTPase activity; negative regulation of interleukin-6 production; negative regulation of interleukin-8 production; negative regulation of neuron apoptotic process; negative regulation of NF-kappaB transcription factor activity; negative regulation of Notch signaling pathway; negative regulation of protein ubiquitination; phototransduction; platelet activation; positive regulation of cell proliferation; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of histone acetylation; positive regulation of histone H4 acetylation; positive regulation of insulin secretion involved in cellular response to glucose stimulus; positive regulation of peptidyl-serine phosphorylation; positive regulation of protein binding; positive regulation of protein phosphorylation; positive regulation of protein ubiquitination; positive regulation of receptor internalization; positive regulation of Rho protein signal transduction; positive regulation of smooth muscle cell apoptotic process; positive regulation of transcription by RNA polymerase II; proteasome-mediated ubiquitin-dependent protein catabolic process; protein transport; protein ubiquitination; response to drug; stress fiber assembly; transcription by RNA polymerase II; ubiquitin-dependent protein catabolic process
Reference #:  P49407-2 (UniProtKB)
Alt. Names/Synonyms: ARB1; ARR1; ARRB1; arrestin 2; Arrestin beta-1; arrestin, beta 1; beta-arrestin; Beta-arrestin-1
Gene Symbols: ARRB1
Molecular weight: 46,309 Da
Basal Isoelectric point: 5.95  Predict pI for various phosphorylation states
CST Pathways:  GPCR Signaling to MAPKs  |  Hedgehog Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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ARRB1 iso2

Protein Structure Not Found.

Cross-references to other databases:  cBioPortal  |  Wikipedia  |  Pfam  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein