ARRB1 - Beta-arrestin-1 - human protein (Function)
 
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ARRB1 »  Beta-arrestin-1
 
Protein also known as:  Arrestin beta-1.
Gene name:  ARRB1
Family name: Arrestin
Entry whose protein(s) existence is based on evidence at protein level
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1 136 2
GENE REF ISO

Function

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Overview 
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. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3.  
19
  • CuratedUniProtKB
GO molecular function 
Alpha-1A adrenergic receptor bindingdefinition[GO:0031691] silver  
  • IEAOrtholog Compara
Alpha-1B adrenergic receptor bindingdefinition[GO:0031692] silver  
  • IEAOrtholog Compara
Angiotensin receptor bindingdefinition[GO:0031701]  
1
  • IPIUniProtKB
AP-2 adaptor complex bindingdefinition[GO:0035612] silver  
  • IEAOrtholog Compara
Clathrin adaptor activitydefinition[GO:0035615] silver  
  • IEAOrtholog Compara
Cysteine-type endopeptidase inhibitor activity involved in apoptotic processdefinition[GO:0043027] silver  
  • IEAOrtholog Compara
Enzyme inhibitor activitydefinition[GO:0004857]  
1
  • TASPINC
Estrogen receptor bindingdefinition[GO:0030331] silver  
  • IEAOrtholog Compara
Follicle-stimulating hormone receptor bindingdefinition[GO:0031762] silver  
  • IEAOrtholog Compara
GTPase activator activitydefinition[GO:0005096]  
1
  • IMPUniProtKB
Not  Histone acetyltransferase activitydefinition[GO:0004402]  
1
  • IDAUniProtKB
Insulin-like growth factor receptor bindingdefinition[GO:0005159]  
1
  • IPIUniProtKB
Ion channel bindingdefinition[GO:0044325] silver  
  • IEAOrtholog Compara
Mitogen-activated protein kinase kinase bindingdefinition[GO:0031434] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
12
  • IPIUniProtKB
  • IPIIntAct
Protein phosphorylated amino acid bindingdefinition[GO:0045309] silver  
  • IEAOrtholog Compara
Transcription factor bindingdefinition[GO:0008134]  
1
  • IPIUniProtKB
Transcription regulatory region DNA bindingdefinition[GO:0044212]  
1
  • IMPBHF-UCL
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • IPIUniProtKB
V2 vasopressin receptor bindingdefinition[GO:0031896] silver  
  • IEAOrtholog Compara
GO biological process 
Activation of MAPK activitydefinition[GO:0000187] silver  
  • IEAOrtholog Compara
Apoptotic DNA fragmentationdefinition[GO:0006309] silver  
  • IEAOrtholog Compara
Follicle-stimulating hormone signaling pathwaydefinition[GO:0042699] silver  
  • IEAOrtholog Compara
G-protein coupled receptor internalizationdefinition[GO:0002031]  
2
  • IMPUniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066] silver  
  • IEAOrtholog Compara
Negative regulation of ERK1 and ERK2 cascadedefinition[GO:0070373] silver  
  • IEAOrtholog Compara
Negative regulation of GTPase activitydefinition[GO:0034260] silver  
  • IEAOrtholog Compara
Negative regulation of interleukin-6 productiondefinition[GO:0032715]  
1
  • IDAUniProtKB
Negative regulation of interleukin-8 productiondefinition[GO:0032717]  
1
  • IDAUniProtKB
Negative regulation of NF-kappaB transcription factor activitydefinition[GO:0032088]  
1
  • IDAUniProtKB
Negative regulation of protein phosphorylationdefinition[GO:0001933] silver  
  • IEAOrtholog Compara
Negative regulation of protein ubiquitinationdefinition[GO:0031397]  
1
  • IDAUniProtKB
Phototransductiondefinition[GO:0007602] silver  
  • IEAOrtholog Compara
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • IDAUniProtKB
Positive regulation of GTPase activitydefinition[GO:0043547]  
1
  • IMPGOC
Positive regulation of histone acetylationdefinition[GO:0035066]  
1
  • IMPBHF-UCL
Positive regulation of histone H4 acetylationdefinition[GO:0090240]  
1
  • IMPUniProtKB
Positive regulation of insulin secretion involved in cellular response to glucose stimulusdefinition[GO:0035774] silver  
  • IEAOrtholog Compara
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138] silver  
  • IEAOrtholog Compara
Positive regulation of protein bindingdefinition[GO:0032092] silver  
  • IEAOrtholog Compara
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IMPUniProtKB
Positive regulation of protein ubiquitinationdefinition[GO:0031398] silver  
  • IEAOrtholog Compara
Positive regulation of receptor internalizationdefinition[GO:0002092]  
1
  • IMPUniProtKB
Positive regulation of Rho protein signal transductiondefinition[GO:0035025]  
1
  • IMPUniProtKB
Positive regulation of smooth muscle cell apoptotic processdefinition[GO:0034393] silver  
  • IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IMPBHF-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic processdefinition[GO:0043161]  
1
  • IMPUniProtKB
Protein transportdefinition[GO:0015031]  
  • IEAUniProtKB KW
Protein ubiquitinationdefinition[GO:0016567]  
1
  • IMPUniProtKB
Stress fiber assemblydefinition[GO:0043149]  
1
  • IMPUniProtKB
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
1
  • IMPUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Chemokine signaling pathway  hsa04062+408  
Endocytosis  hsa04144+408  
MAPK signaling pathway  hsa04010+408  
Phototransduction  hsa04744+408  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Hemostasis  REACT_604  
Membrane Trafficking  REACT_11123  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Protein transport  definition   [KW-0653]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Transport  definition   [KW-0813]
Molecular function 
Signal transduction inhibitor  definition   [KW-0734]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: Arrestin_beta_1
GenomeRNAi: 408
PRO: PR:P49407