UniProt Accession

 ARRB1_HUMAN; P49407; B6V9G8; O75625; O75630; Q2PP20; Q9BTK8 

Genbank Protein ID

 L04685; L04685; AF084040; AF084940; DQ314865; FJ348262; CH471076; BC003636 

Genbank Nucleotide ID

 AAA35559.1; AAA35558.1; AAC33295.1; AAC34123.1; ABC40724.1; ACI96306.1; EAW74962.1; AAH03636.1 

Protein Name

 Beta-arrestin-1 

Protein Synonyms/Alias

 Arrestin beta-1 

Gene Name

 ARRB1 

Gene Synonyms/Alias

 ARR1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
49	LVDPEYLKERRVYVT	ubiquitination	[1]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

Functional Description

 Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G- protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta- arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. 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. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta- arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for which the beta-arrestin- mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha- thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1- stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 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) (By similarity). Involved in IL8-mediated granule release in neutrophils. 

Sequence Annotation

 REGION 1 163 Interaction with SRC (By similarity).
 REGION 45 86 Interaction with CHRM2 (By similarity).
 REGION 318 418 Interaction with TRAF6.
 MOTIF 385 395 [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif.
 BINDING 250 250 Inositol hexakisphosphate (By
 BINDING 255 255 Inositol hexakisphosphate (By
 BINDING 324 324 Inositol hexakisphosphate (By
 BINDING 326 326 Inositol hexakisphosphate (By
 MOD_RES 47 47 Phosphotyrosine (By similarity).
 MOD_RES 412 412 Phosphoserine; by GRK5.  

Keyword

 3D-structure; Alternative splicing; Cell membrane; Cell projection; Coated pit; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Membrane; Nucleus; Phosphoprotein; Protein transport; Reference proteome; Signal transduction inhibitor; Transcription; Transcription regulation; Transport; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 418 AA 

Protein Sequence

Gene Ontology

 GO:0000785; C:chromatin; IDA:BHF-UCL.
 GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
 GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0000139; C:Golgi membrane; TAS:Reactome.
 GO:0005765; C:lysosomal membrane; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; TAS:ProtInc.
 GO:0031143; C:pseudopodium; IEA:UniProtKB-SubCell.
 GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IEA:Compara.
 GO:0004857; F:enzyme inhibitor activity; TAS:ProtInc.
 GO:0005096; F:GTPase activator activity; IMP:UniProtKB.
 GO:0044212; F:transcription regulatory region DNA binding; IMP:BHF-UCL.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0002031; P:G-protein coupled receptor internalization; IMP:UniProtKB.
 GO:0032715; P:negative regulation of interleukin-6 production; IDA:UniProtKB.
 GO:0032717; P:negative regulation of interleukin-8 production; IDA:UniProtKB.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
 GO:0007219; P:Notch signaling pathway; TAS:Reactome.
 GO:0007602; P:phototransduction; IEA:Compara.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
 GO:0090240; P:positive regulation of histone H4 acetylation; IMP:UniProtKB.
 GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Compara.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Compara.
 GO:0032092; P:positive regulation of protein binding; IEA:Compara.
 GO:0035025; P:positive regulation of Rho protein signal transduction; IMP:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
 GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
 GO:0015031; P:protein transport; IEA:UniProtKB-KW.
 GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
 GO:0043149; P:stress fiber assembly; IMP:UniProtKB.
 GO:0006366; P:transcription from RNA polymerase II promoter; IMP:UniProtKB. 

Interpro

 IPR000698; Arrestin.
 IPR011021; Arrestin-like_N.
 IPR014752; Arrestin_C.
 IPR011022; Arrestin_C-like.
 IPR017864; Arrestin_CS.
 IPR014753; Arrestin_N.
 IPR014756; Ig_E-set. 

Pfam

 PF02752; Arrestin_C
 PF00339; Arrestin_N 

SMART

 SM01017; Arrestin_C 

PROSITE

 PS00295; ARRESTINS 

PRINTS

 PR00309; ARRESTIN.