Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009921
UniProt IDP49407
Primary gene name(s)ARRB1
Synonym gene name(s)ARR1
Protein nameBeta-arrestin-1
Protein functionFunctions 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. {ECO:0000250, ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15611106, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:18337459, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23633677}.
Subcellular locationCytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit {ECO:0000305}. Cell projection, pseudopodium {ECO:0000250}. Cytoplasmic vesicle. 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}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P49407
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
follicle-stimulating hormone signaling pathway [GO:0042699];
G-protein coupled receptor internalization [GO:0002031];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of GTPase activity [GO:0034260];
negative regulation of interleukin-6 production [GO:0032715];
negative regulation of interleukin-8 production [GO:0032717];
negative regulation of NF-kappaB transcription factor activity [GO:0032088];
negative regulation of protein ubiquitination [GO:0031397];
phototransduction [GO:0007602];
platelet activation [GO:0030168];
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of histone acetylation [GO:0035066];
positive regulation of histone H4 acetylation [GO:0090240];
positive regulation of insulin secretion involved in cellular response to glucose stimulus [GO:0035774];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of protein binding [GO:0032092];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of protein ubiquitination [GO:0031398];
positive regulation of receptor internalization [GO:0002092];
positive regulation of Rho protein signal transduction [GO:0035025];
positive regulation of smooth muscle cell apoptotic process [GO:0034393];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein transport [GO:0015031];
protein ubiquitination [GO:0016567];
stress fiber assembly [GO:0043149];
transcription from RNA polymerase II promoter [GO:0006366]
Gene Ontology
(Molecular Function)
Complete annatation
angiotensin receptor binding [GO:0031701];
cysteine-type endopeptidase inhibitor activity involved in apoptotic process [GO:0043027];
enzyme inhibitor activity [GO:0004857];
GTPase activator activity [GO:0005096];
insulin-like growth factor receptor binding [GO:0005159];
transcription factor binding [GO:0008134];
transcription regulatory region DNA binding [GO:0044212];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
basolateral plasma membrane [GO:0016323];
chromatin [GO:0000785];
coated pit [GO:0005905];
cytoplasm [GO:0005737];
cytoplasmic vesicle [GO:0031410];
cytoplasmic vesicle membrane [GO:0030659];
cytosol [GO:0005829];
dendritic spine [GO:0043197];
Golgi membrane [GO:0000139];
lysosomal membrane [GO:0005765];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
postsynaptic density [GO:0014069];
postsynaptic membrane [GO:0045211];
pseudopodium [GO:0031143]
Protein-protein interaction106901
Phylogenetic treeP49407
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-1.613110366135531.60963493622823e-061.19922974586416e-05
AZA vs. DISU-0.4166955100172990.100511425374350.641773180085401
AZA vs. IL7-0.05384159041326120.7801727062519120.999311006273513
AZA vs. SAHA-0.6504830928962740.008418334139145720.0872750817149124
DISU vs. CD31.18523963516780.001281279195200270.00512443687674419
DISU vs. IL70.3537435826679080.1615896510173910.521017966507434
DISU vs. SAHA-0.2327937056259120.4280157578069710.776911552450292
DMSO vs. AZA-0.02454334183626160.8840544765778761
DMSO vs. CD31.576981935348611.50170028567764e-061.03966520237747e-05
DMSO vs. DISU0.3901938645706870.1109752515913770.586319898851999
DMSO vs. IL7-0.02191404466717240.9032805342128710.979523619218739
DMSO vs. SAHA-0.6329198765659010.007785743012666990.0763428321040366
HIV vs. Mock in Activation0.08313130350412420.8943550463719660.999983755607037
HIV vs. Mock in Latency-0.07922090696732620.6332763577383140.999834320637052
IL7 vs. CD31.566974380367731.93732130571167e-061.76977236612073e-05
SAHA vs. CD30.9375052664389890.008751904321849910.0229535673738737
SAHA vs. IL7-0.6015419937419890.0142456207667120.0800367079528202
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -1.28587 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2IV8 X-ray 2.8Å P/Q=383-402.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat activates 17855543

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04740 Olfactory transduction - Homo sapiens (human)
hsa05032 Morphine addiction - Homo sapiens (human)