Version 5.4
Bos taurus Protein: ARRB1
Summary
InnateDB Protein IDBP-687437.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol ARRB1
Protein Name Beta-arrestin-1
Synonyms
Species Bos taurus
Ensembl Protein ENSBTAP00000027296
InnateDB Gene IDBG-635576 (ARRB1)
Protein Structure
UniProt Annotation
Function 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. Involved in IL8-mediated granule release in neutrophils. Binds phosphoinositides. Binds inositol hexakisphosphate (InsP6) (By similarity). 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 (By similarity). {ECO:0000250}.
Subcellular Localization Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit {ECO:0000305}. Cell projection, pseudopodium {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Note=Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs. The monomeric form is predominantly located in the nucleus. The oligomeric form is located in the cytoplasm. Translocates to the nucleus upon stimulation of OPRD1 (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Beta-arrestin 1A is found in cortex, cerebellum, striatum, pineal gland, retina and heart. Beta- arrestin 1B is found in spleen, lung, pituitary and kidney.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 216 interaction(s) predicted by orthology.
Predicted by orthology
Total 216 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005096 GTPase activator activity
GO:0005159 insulin-like growth factor receptor binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0031434 mitogen-activated protein kinase kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0031701 angiotensin receptor binding
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process
GO:0044212 transcription regulatory region DNA binding
Biological Process
GO:0001934 positive regulation of protein phosphorylation
GO:0002031 G-protein coupled receptor internalization
GO:0002092 positive regulation of receptor internalization
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006810 transport
GO:0007165 signal transduction
GO:0007602 phototransduction
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway
GO:0009968 negative regulation of signal transduction
GO:0015031 protein transport
GO:0016567 protein ubiquitination
GO:0031397 negative regulation of protein ubiquitination
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032092 positive regulation of protein binding
GO:0032715 negative regulation of interleukin-6 production
GO:0032717 negative regulation of interleukin-8 production
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0035025 positive regulation of Rho protein signal transduction
GO:0035066 positive regulation of histone acetylation
GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0043149 stress fiber assembly
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043547 positive regulation of GTPase activity
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0090240 positive regulation of histone H4 acetylation
Cellular Component
GO:0000785 chromatin
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005905 coated pit
GO:0016020 membrane
GO:0016023 cytoplasmic membrane-bounded vesicle
GO:0031143 pseudopodium
GO:0031410 cytoplasmic vesicle
GO:0042995 cell projection
Protein Structure and Domains
PDB ID
InterPro IPR000698 Arrestin
IPR011021 Arrestin-like, N-terminal
IPR011022 Arrestin C-terminal-like domain
IPR014756 Immunoglobulin E-set
PFAM PF00339
PF02752
PRINTS PR00309
PIRSF
SMART SM01017
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P17870
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 281637
UniGene Bt.52082
RefSeq NP_776668
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL M33601
GenPept AAA30387

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca