ARRB1_HUMAN
ID ARRB1_HUMAN Reviewed; 418 AA.
AC P49407; B6V9G8; O75625; O75630; Q2PP20; Q9BTK8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 05-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Beta-arrestin-1;
DE AltName: Full=Arrestin beta-1;
DE AltName: Full=Non-visual arrestin-2 {ECO:0000303|PubMed:23886940};
GN Name=ARRB1; Synonyms=ARR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B).
RC TISSUE=Peripheral blood;
RX PubMed=8486659; DOI=10.1016/s0021-9258(18)98412-7;
RA Parruti G., Peracchia F., Sallese M., Ambrosini G., Masini M., Rotilio D.,
RA de Blasi A.;
RT "Molecular analysis of human beta-arrestin-1: cloning, tissue distribution,
RT and regulation of expression. Identification of two isoforms generated by
RT alternative splicing.";
RL J. Biol. Chem. 268:9753-9761(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B).
RC TISSUE=Brain;
RA Yu Q.M., Zhou T.H., Cheng Z.J., Ma L., Pei G.;
RT "Molecular cloning of two isoforms of human beta-arrestin 1.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1B).
RC TISSUE=Lung;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RT "Isolation of cDNA coding for Homo sapiens arrestin, beta 1 (ARRB1),
RT transcript variant 2.";
RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1A).
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH CCR2 AND GRK2.
RX PubMed=9501202; DOI=10.1073/pnas.95.6.2985;
RA Aragay A.M., Mellado M., Frade J.M., Martin A.M., Jimenez-Sainz M.C.,
RA Martinez-A C., Mayor F. Jr.;
RT "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization
RT mediated by the G protein-coupled receptor kinase 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2985-2990(1998).
RN [8]
RP MUTAGENESIS OF ARG-169.
RX PubMed=10066734; DOI=10.1074/jbc.274.11.6831;
RA Kovoor A., Celver J., Abdryashitov R.I., Chavkin C., Gurevich V.V.;
RT "Targeted construction of phosphorylation-independent beta-arrestin mutants
RT with constitutive activity in cells.";
RL J. Biol. Chem. 274:6831-6834(1999).
RN [9]
RP INTERACTION WITH ADRB2, AND SUBCELLULAR LOCATION.
RX PubMed=9924018; DOI=10.1126/science.283.5402.655;
RA Luttrell L.M., Ferguson S.S.G., Daaka Y., Miller W.E., Maudsley S.,
RA Della Rocca G.J., Lin F.-T., Kawakatsu H., Owada K., Luttrell D.K.,
RA Caron M.G., Lefkowitz R.J.;
RT "Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein
RT kinase complexes.";
RL Science 283:655-661(1999).
RN [10]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH ANTAGONIST-STIMULATED GPCRS.
RX PubMed=10748214; DOI=10.1074/jbc.m910348199;
RA Oakley R.H., Laporte S.A., Holt J.A., Caron M.G., Barak L.S.;
RT "Differential affinities of visual arrestin, beta arrestin1, and beta
RT arrestin2 for G protein-coupled receptors delineate two major classes of
RT receptors.";
RL J. Biol. Chem. 275:17201-17210(2000).
RN [11]
RP INTERACTION WITH HCK AND CXCR1.
RX PubMed=10973280; DOI=10.1038/79767;
RA Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E., Xu L.,
RA Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.;
RT "Regulation of tyrosine kinase activation and granule release through beta-
RT arrestin by CXCRI.";
RL Nat. Immunol. 1:227-233(2000).
RN [12]
RP FUNCTION IN INTERNALIZATION OF C5AR1, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH C5AR1.
RX PubMed=12464600; DOI=10.1074/jbc.m210120200;
RA Braun L., Christophe T., Boulay F.;
RT "Phosphorylation of key serine residues is required for internalization of
RT the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin,
RT dynamin, and clathrin-dependent pathway.";
RL J. Biol. Chem. 278:4277-4285(2003).
RN [13]
RP FUNCTION IN UBIQUITINATION OF IGF1R, AND INTERACTION WITH IGF1R AND MDM2.
RX PubMed=15878855; DOI=10.1074/jbc.m501129200;
RA Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A.,
RA Lefkowitz R.J., Larsson O.;
RT "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the
RT insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3
RT ligase.";
RL J. Biol. Chem. 280:24412-24419(2005).
RN [14]
RP FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
RX PubMed=14711824; DOI=10.1074/jbc.c300443200;
RA Ahn S., Wei H., Garrison T.R., Lefkowitz R.J.;
RT "Reciprocal regulation of angiotensin receptor-activated extracellular
RT signal-regulated kinases by beta-arrestins 1 and 2.";
RL J. Biol. Chem. 279:7807-7811(2004).
RN [15]
RP NUCLEAR FUNCTION IN TRANSCRIPTIONAL REGULATION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH CREB1.
RX PubMed=16325578; DOI=10.1016/j.cell.2005.09.011;
RA Kang J., Shi Y., Xiang B., Qu B., Su W., Zhu M., Zhang M., Bao G., Wang F.,
RA Zhang X., Yang R., Fan F., Chen X., Pei G., Ma L.;
RT "A nuclear function of beta-arrestin1 in GPCR signaling: regulation of
RT histone acetylation and gene transcription.";
RL Cell 123:833-847(2005).
RN [16]
RP FUNCTION IN CYTOSKELETAL REARRANGEMENT, AND SUBCELLULAR LOCATION.
RX PubMed=15611106; DOI=10.1074/jbc.m412924200;
RA Barnes W.G., Reiter E., Violin J.D., Ren X.-R., Milligan G.,
RA Lefkowitz R.J.;
RT "beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber
RT formation following receptor stimulation.";
RL J. Biol. Chem. 280:8041-8050(2005).
RN [17]
RP FUNCTION IN INTERNALIZATION OF CCR5, AND INTERACTION WITH CCR5.
RX PubMed=16144840; DOI=10.1074/jbc.m500535200;
RA Huettenrauch F., Pollok-Kopp B., Oppermann M.;
RT "G protein-coupled receptor kinases promote phosphorylation and beta-
RT arrestin-mediated internalization of CCR5 homo- and hetero-oligomers.";
RL J. Biol. Chem. 280:37503-37515(2005).
RN [18]
RP FUNCTION IN F2LR1-MEDIATED ERK SIGNALING, AND SUBCELLULAR LOCATION.
RX PubMed=15475570; DOI=10.1124/mol.104.006072;
RA Stalheim L., Ding Y., Gullapalli A., Paing M.M., Wolfe B.L., Morris D.R.,
RA Trejo J.;
RT "Multiple independent functions of arrestins in the regulation of protease-
RT activated receptor-2 signaling and trafficking.";
RL Mol. Pharmacol. 67:78-87(2005).
RN [19]
RP FUNCTION IN AVPR2-MEDIATED ERK SIGNALING.
RX PubMed=15671180; DOI=10.1073/pnas.0409534102;
RA Ren X.-R., Reiter E., Ahn S., Kim J., Chen W., Lefkowitz R.J.;
RT "Different G protein-coupled receptor kinases govern G protein and beta-
RT arrestin-mediated signaling of V2 vasopressin receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1448-1453(2005).
RN [20]
RP INTERACTION WITH AP2B1, AND MUTAGENESIS OF PHE-388; ASP-390 AND ARG-393.
RX PubMed=16516836; DOI=10.1016/j.devcel.2006.01.016;
RA Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M.,
RA Roth R., Heuser J.E., Owen D.J., Traub L.M.;
RT "Molecular switches involving the AP-2 beta2 appendage regulate endocytic
RT cargo selection and clathrin coat assembly.";
RL Dev. Cell 10:329-342(2006).
RN [21]
RP FUNCTION IN ADRB2-MEDIATED ERK SIGNALING, AND SUBCELLULAR LOCATION.
RX PubMed=16280323; DOI=10.1074/jbc.m506576200;
RA Shenoy S.K., Drake M.T., Nelson C.D., Houtz D.A., Xiao K., Madabushi S.,
RA Reiter E., Premont R.T., Lichtarge O., Lefkowitz R.J.;
RT "beta-arrestin-dependent, G protein-independent ERK1/2 activation by the
RT beta2 adrenergic receptor.";
RL J. Biol. Chem. 281:1261-1273(2006).
RN [22]
RP FUNCTION IN PTH1R-MEDIATED ERK SIGNALING.
RX PubMed=16492667; DOI=10.1074/jbc.m513380200;
RA Gesty-Palmer D., Chen M., Reiter E., Ahn S., Nelson C.D., Wang S.,
RA Eckhardt A.E., Cowan C.L., Spurney R.F., Luttrell L.M., Lefkowitz R.J.;
RT "Distinct beta-arrestin- and G protein-dependent pathways for parathyroid
RT hormone receptor-stimulated ERK1/2 activation.";
RL J. Biol. Chem. 281:10856-10864(2006).
RN [23]
RP FUNCTION IN INTERNALIZATION OF PTAFR, FUNCTION IN THE P38 MAPK SIGNALING
RP PATHWAY, FUNCTION IN ACTIN BUNDLE FORMATION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH PTAFR AND MAP2K3.
RX PubMed=16709866; DOI=10.4049/jimmunol.176.11.7039;
RA McLaughlin N.J., Banerjee A., Kelher M.R., Gamboni-Robertson F., Hamiel C.,
RA Sheppard F.R., Moore E.E., Silliman C.C.;
RT "Platelet-activating factor-induced clathrin-mediated endocytosis requires
RT beta-arrestin-1 recruitment and activation of the p38 MAPK signalosome at
RT the plasma membrane for actin bundle formation.";
RL J. Immunol. 176:7039-7050(2006).
RN [24]
RP FUNCTION IN TLR/IL-1 RECEPTOR SIGNALING, AND INTERACTION WITH TRAF6.
RX PubMed=16378096; DOI=10.1038/ni1294;
RA Wang Y., Tang Y., Teng L., Wu Y., Zhao X., Pei G.;
RT "Association of beta-arrestin and TRAF6 negatively regulates Toll-like
RT receptor-interleukin 1 receptor signaling.";
RL Nat. Immunol. 7:139-147(2006).
RN [25]
RP INTERACTION WITH GPR143.
RX PubMed=16524428; DOI=10.1111/j.1600-0749.2006.00292.x;
RA Innamorati G., Piccirillo R., Bagnato P., Palmisano I., Schiaffino M.V.;
RT "The melanosomal/lysosomal protein OA1 has properties of a G protein-
RT coupled receptor.";
RL Pigment Cell Res. 19:125-135(2006).
RN [26]
RP INTERACTION WITH AP2B1.
RX PubMed=17456551; DOI=10.1242/jcs.03444;
RA Fessart D., Simaan M., Zimmerman B., Comeau J., Hamdan F.F., Wiseman P.W.,
RA Bouvier M., Laporte S.A.;
RT "Src-dependent phosphorylation of beta2-adaptin dissociates the beta-
RT arrestin-AP-2 complex.";
RL J. Cell Sci. 120:1723-1732(2007).
RN [27]
RP FUNCTION IN BETA-ADRENERGIC RECEPTOR REGULATION.
RX PubMed=18337459; DOI=10.1096/fj.07-102459;
RA Deshpande D.A., Theriot B.S., Penn R.B., Walker J.K.;
RT "Beta-arrestins specifically constrain beta2-adrenergic receptor signaling
RT and function in airway smooth muscle.";
RL FASEB J. 22:2134-2141(2008).
RN [28]
RP FUNCTION IN INTERNALIZATION OF OPRD1.
RX PubMed=18419762; DOI=10.1111/j.1471-4159.2008.05431.x;
RA Zhang X., Wang F., Chen X., Chen Y., Ma L.;
RT "Post-endocytic fates of delta-opioid receptor are regulated by GRK2-
RT mediated receptor phosphorylation and distinct beta-arrestin isoforms.";
RL J. Neurochem. 106:781-792(2008).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [30]
RP FUNCTION IN INTERNALIZATION OF CCR2.
RX PubMed=19643177; DOI=10.1016/j.cellsig.2009.07.010;
RA Garcia Lopez M.A., Aguado Martinez A., Lamaze C., Martinez-Alonso C.,
RA Fischer T.;
RT "Inhibition of dynamin prevents CCL2-mediated endocytosis of CCR2 and
RT activation of ERK1/2.";
RL Cell. Signal. 21:1748-1757(2009).
RN [31]
RP PHOSPHORYLATION AT SER-412.
RX PubMed=19661922; DOI=10.1038/emboj.2009.215;
RA Barthet G., Carrat G., Cassier E., Barker B., Gaven F., Pillot M.,
RA Framery B., Pellissier L.P., Augier J., Kang D.S., Claeysen S., Reiter E.,
RA Baneres J.L., Benovic J.L., Marin P., Bockaert J., Dumuis A.;
RT "Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-
RT HT4 receptor signalling.";
RL EMBO J. 28:2706-2718(2009).
RN [32]
RP INTERACTION WITH MAP2K4/MKK4.
RX PubMed=19782076; DOI=10.1016/j.febslet.2009.09.035;
RA Li X., MacLeod R., Dunlop A.J., Edwards H.V., Advant N., Gibson L.C.,
RA Devine N.M., Brown K.M., Adams D.R., Houslay M.D., Baillie G.S.;
RT "A scanning peptide array approach uncovers association sites within the
RT JNK/beta arrestin signalling complex.";
RL FEBS Lett. 583:3310-3316(2009).
RN [33]
RP FUNCTION IN MIP-1-BETA-STIMULATED CHEMOTAXIS.
RX PubMed=19620252; DOI=10.1189/jlb.0908551;
RA Cheung R., Malik M., Ravyn V., Tomkowicz B., Ptasznik A., Collman R.G.;
RT "An arrestin-dependent multi-kinase signaling complex mediates MIP-
RT 1beta/CCL4 signaling and chemotaxis of primary human macrophages.";
RL J. Leukoc. Biol. 86:833-845(2009).
RN [34]
RP UBIQUITINATION, DEUBIQUITINATION BY USP33, AND INTERACTION WITH USP33.
RX PubMed=19363159; DOI=10.1073/pnas.0901083106;
RA Shenoy S.K., Modi A.S., Shukla A.K., Xiao K., Berthouze M., Ahn S.,
RA Wilkinson K.D., Miller W.E., Lefkowitz R.J.;
RT "Beta-arrestin-dependent signaling and trafficking of 7-transmembrane
RT receptors is reciprocally regulated by the deubiquitinase USP33 and the E3
RT ligase Mdm2.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6650-6655(2009).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [36]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [38]
RP FUNCTION, AND INTERACTION WITH ACKR3.
RX PubMed=22457824; DOI=10.1371/journal.pone.0034192;
RA Canals M., Scholten D.J., de Munnik S., Han M.K., Smit M.J., Leurs R.;
RT "Ubiquitination of CXCR7 controls receptor trafficking.";
RL PLoS ONE 7:E34192-E34192(2012).
RN [39]
RP FUNCTION, AND INTERACTION WITH ACKR4.
RX PubMed=23341447; DOI=10.1074/jbc.m112.406108;
RA Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M.,
RA van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J.,
RA Vischer H.F.;
RT "Beta-arrestin recruitment and G protein signaling by the atypical human
RT chemokine decoy receptor CCX-CKR.";
RL J. Biol. Chem. 288:7169-7181(2013).
RN [40]
RP FUNCTION, AND INTERACTION WITH ARRDC1.
RX PubMed=23886940; DOI=10.1242/jcs.130500;
RA Puca L., Chastagner P., Meas-Yedid V., Israel A., Brou C.;
RT "Alpha-arrestin 1 (ARRDC1) and beta-arrestins cooperate to mediate Notch
RT degradation in mammals.";
RL J. Cell Sci. 126:4457-4468(2013).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [42]
RP FUNCTION.
RX PubMed=23633677; DOI=10.1126/scisignal.2003627;
RA Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B.,
RA Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R.,
RA Locati M.;
RT "Beta-arrestin-dependent activation of the cofilin pathway is required for
RT the scavenging activity of the atypical chemokine receptor D6.";
RL Sci. Signal. 6:RA30-RA30(2013).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [44]
RP INTERACTION WITH GPR61; GPR62 AND GPR135.
RX PubMed=28827538; DOI=10.1038/s41598-017-08996-7;
RA Oishi A., Karamitri A., Gerbier R., Lahuna O., Ahmad R., Jockers R.;
RT "Orphan GPR61, GPR62 and GPR135 receptors and the melatonin MT2 receptor
RT reciprocally modulate their signaling functions.";
RL Sci. Rep. 7:8990-8990(2017).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 383-402 IN COMPLEX WITH AP2B1.
RX PubMed=16903783; DOI=10.1371/journal.pbio.0040262;
RA Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y.,
RA Mills I.G., Benmerah A., McMahon H.T.;
RT "Role of the AP2 beta-appendage hub in recruiting partners for clathrin-
RT coated vesicle assembly.";
RL PLoS Biol. 4:E262-E262(2006).
CC -!- FUNCTION: Functions in regulating agonist-mediated G-protein coupled
CC receptor (GPCR) signaling by mediating both receptor desensitization
CC and resensitization processes. During homologous desensitization, beta-
CC arrestins bind to the GPRK-phosphorylated receptor and sterically
CC preclude its coupling to the cognate G-protein; the binding appears to
CC require additional receptor determinants exposed only in the active
CC receptor conformation. The beta-arrestins target many receptors for
CC internalization by acting as endocytic adapters (CLASPs, clathrin-
CC associated sorting proteins) and recruiting the GPRCs to the adapter
CC protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the
CC extent of beta-arrestin involvement appears to vary significantly
CC depending on the receptor, agonist and cell type. Internalized
CC arrestin-receptor complexes traffic to intracellular endosomes, where
CC they remain uncoupled from G-proteins. Two different modes of arrestin-
CC mediated internalization occur. Class A receptors, like ADRB2, OPRM1,
CC ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the
CC plasma membrane and undergo rapid recycling. Class B receptors, like
CC AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with
CC arrestin and traffic with it to endosomal vesicles, presumably as
CC desensitized receptors, for extended periods of time. Receptor
CC resensitization then requires that receptor-bound arrestin is removed
CC so that the receptor can be dephosphorylated and returned to the plasma
CC membrane. Involved in internalization of P2RY4 and UTP-stimulated
CC internalization of P2RY2. Involved in phosphorylation-dependent
CC internalization of OPRD1 ands subsequent recycling. Involved in the
CC degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-
CC activated receptors. Beta-arrestins function as multivalent adapter
CC proteins that can switch the GPCR from a G-protein signaling mode that
CC transmits short-lived signals from the plasma membrane via small
CC molecule second messengers and ion channels to a beta-arrestin
CC signaling mode that transmits a distinct set of signals that are
CC initiated as the receptor internalizes and transits the intracellular
CC compartment. Acts as signaling scaffold for MAPK pathways such as
CC MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is
CC largely excluded from the nucleus and confined to cytoplasmic locations
CC such as endocytic vesicles, also called beta-arrestin signalosomes.
CC Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for
CC which the beta-arrestin-mediated signaling relies on both ARRB1 and
CC ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some
CC GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or
CC ARRB2 and is inhibited by the other respective beta-arrestin form
CC (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-
CC mediated activation (reciprocal regulation). Is required for SP-
CC stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized
CC NK1R resulting in ERK1/2 activation, which is required for the
CC antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-
CC mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway.
CC Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in
CC IGF1-stimulated AKT1 signaling leading to increased protection from
CC apoptosis. Involved in activation of the p38 MAPK signaling pathway and
CC in actin bundle formation. Involved in F2RL1-mediated cytoskeletal
CC rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber
CC formation by acting together with GNAQ to activate RHOA. Appears to
CC function as signaling scaffold involved in regulation of MIP-1-beta-
CC stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-
CC kappa-B-dependent transcription in response to GPCR or cytokine
CC stimulation by interacting with and stabilizing CHUK. May serve as
CC nuclear messenger for GPCRs. Involved in OPRD1-stimulated
CC transcriptional regulation by translocating to CDKN1B and FOS promoter
CC regions and recruiting EP300 resulting in acetylation of histone H4.
CC Involved in regulation of LEF1 transcriptional activity via interaction
CC with DVL1 and/or DVL2 Also involved in regulation of receptors other
CC than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling
CC through the interaction with TRAF6 which prevents TRAF6
CC autoubiquitination and oligomerization required for activation of NF-
CC kappa-B and JUN. Binds phosphoinositides. Binds
CC inositolhexakisphosphate (InsP6) (By similarity). Involved in IL8-
CC mediated granule release in neutrophils. Required for atypical
CC chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent
CC phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2
CC from endosomal compartment to cell membrane, increasing its efficiency
CC in chemokine uptake and degradation. Involved in the internalization of
CC the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH
CC signaling pathway by mediating the ubiquitination and degradation of
CC NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-
CC protein ligase to the receptor (PubMed:23886940). {ECO:0000250,
CC ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:14711824,
CC ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15611106,
CC ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15878855,
CC ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323,
CC ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667,
CC ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:18337459,
CC ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:19620252,
CC ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:22457824,
CC ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23633677,
CC ECO:0000269|PubMed:23886940}.
CC -!- SUBUNIT: Monomer. Homodimer. Homooligomer; the self-association is
CC mediated by InsP6-binding. Heterooligomer with ARRB2; the association
CC is mediated by InsP6-binding. Interacts with GPR143. Interacts with
CC ADRB2 (phosphorylated). Interacts with CHRM2 (phosphorylated).
CC Interacts with LHCGR. Interacts with CYTH2 and CASR. Interacts with
CC AP2B1 (dephosphorylated at 'Tyr-737'); phosphorylation of AP2B1 at
CC 'Tyr-737' disrupts the interaction. Interacts (dephosphorylated at Ser-
CC 412) with CLTC. Interacts with CCR2 and GRK2. Interacts with CRR5.
CC Interacts with PTAFR (phosphorylated on serine residues). Interacts
CC with CLTC and MAP2K3. Interacts with CREB1. Interacts with TRAF6.
CC Interacts with IGF1R and MDM2. Interacts with C5AR1. Interacts with
CC PDE4D. Interacts with SRC (via the SH3 domain and the protein kinase
CC domain); the interaction is independent of the phosphorylation state of
CC SRC C-terminus. Interacts with TACR1. Interacts with RAF1. Interacts
CC with CHUK, IKBKB and MAP3K14. Interacts with DVL1; the interaction is
CC enhanced by phosphorylation of DVL1. Interacts with DVL2; the
CC interaction is enhanced by phosphorylation of DVL2. Interacts with
CC IGF1R. Associates with MAP kinase p38. Part of a MAPK signaling complex
CC consisting of TACR1, ARRB1, SRC, MAPK1 (activated) and MAPK3
CC (activated). Part of a MAPK signaling complex consisting of F2RL1,
CC ARRB1, RAF1, MAPK1 (activated) and MAPK3 (activated) (By similarity).
CC Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1
CC (phosphorylated). Interacts with ACKR3 and ACKR4. Interacts with
CC ARRDC1; the interaction is direct (PubMed:23886940). Interacts with
CC GPR61, GPR62 and GPR135 (PubMed:28827538). {ECO:0000250,
CC ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:12464600,
CC ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840,
CC ECO:0000269|PubMed:16325578, ECO:0000269|PubMed:16378096,
CC ECO:0000269|PubMed:16516836, ECO:0000269|PubMed:16524428,
CC ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:16903783,
CC ECO:0000269|PubMed:17456551, ECO:0000269|PubMed:19363159,
CC ECO:0000269|PubMed:19782076, ECO:0000269|PubMed:22457824,
CC ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23886940,
CC ECO:0000269|PubMed:28827538, ECO:0000269|PubMed:9501202,
CC ECO:0000269|PubMed:9924018}.
CC -!- INTERACTION:
CC P49407; P63010-2: AP2B1; NbExp=3; IntAct=EBI-743313, EBI-11529439;
CC P49407; O15169: AXIN1; NbExp=2; IntAct=EBI-743313, EBI-710484;
CC P49407; P62158: CALM3; NbExp=3; IntAct=EBI-743313, EBI-397435;
CC P49407; P20963: CD247; NbExp=9; IntAct=EBI-743313, EBI-1165705;
CC P49407; P25101: EDNRA; NbExp=3; IntAct=EBI-743313, EBI-6624559;
CC P49407; P50148: GNAQ; NbExp=2; IntAct=EBI-743313, EBI-3909604;
CC P49407; Q5JWF2: GNAS; NbExp=5; IntAct=EBI-743313, EBI-4400880;
CC P49407; Q14749: GNMT; NbExp=12; IntAct=EBI-743313, EBI-744239;
CC P49407; P06396: GSN; NbExp=3; IntAct=EBI-743313, EBI-351506;
CC P49407; Q16665: HIF1A; NbExp=3; IntAct=EBI-743313, EBI-447269;
CC P49407; P11142: HSPA8; NbExp=4; IntAct=EBI-743313, EBI-351896;
CC P49407; Q99683: MAP3K5; NbExp=3; IntAct=EBI-743313, EBI-476263;
CC P49407; P53779: MAPK10; NbExp=2; IntAct=EBI-743313, EBI-713543;
CC P49407; P45984: MAPK9; NbExp=9; IntAct=EBI-743313, EBI-713568;
CC P49407; Q00987: MDM2; NbExp=3; IntAct=EBI-743313, EBI-389668;
CC P49407; P19338: NCL; NbExp=3; IntAct=EBI-743313, EBI-346967;
CC P49407; Q14978: NOLC1; NbExp=3; IntAct=EBI-743313, EBI-396155;
CC P49407; P14618: PKM; NbExp=3; IntAct=EBI-743313, EBI-353408;
CC P49407; P14859-6: POU2F1; NbExp=3; IntAct=EBI-743313, EBI-11526590;
CC P49407; P35813: PPM1A; NbExp=4; IntAct=EBI-743313, EBI-989143;
CC P49407; O75688: PPM1B; NbExp=4; IntAct=EBI-743313, EBI-1047039;
CC P49407; Q13523: PRPF4B; NbExp=2; IntAct=EBI-743313, EBI-395940;
CC P49407; P06702: S100A9; NbExp=2; IntAct=EBI-743313, EBI-1055001;
CC P49407; P12931: SRC; NbExp=3; IntAct=EBI-743313, EBI-621482;
CC P49407; Q15208: STK38; NbExp=3; IntAct=EBI-743313, EBI-458376;
CC P49407; Q13428: TCOF1; NbExp=3; IntAct=EBI-743313, EBI-396105;
CC P49407; P04637: TP53; NbExp=5; IntAct=EBI-743313, EBI-366083;
CC P49407; P27348: YWHAQ; NbExp=3; IntAct=EBI-743313, EBI-359854;
CC P49407; P25490: YY1; NbExp=4; IntAct=EBI-743313, EBI-765538;
CC P49407; O43298: ZBTB43; NbExp=5; IntAct=EBI-743313, EBI-740718;
CC P49407; O95218: ZRANB2; NbExp=4; IntAct=EBI-743313, EBI-1051583;
CC P49407; Q7DB77: tir; Xeno; NbExp=3; IntAct=EBI-743313, EBI-6480811;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane. Membrane,
CC clathrin-coated pit {ECO:0000305}. Cell projection, pseudopodium
CC {ECO:0000250}. Cytoplasmic vesicle. Note=Translocates to the plasma
CC membrane and colocalizes with antagonist-stimulated GPCRs. The
CC monomeric form is predominantly located in the nucleus. The oligomeric
CC form is located in the cytoplasm. Translocates to the nucleus upon
CC stimulation of OPRD1 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1A;
CC IsoId=P49407-1; Sequence=Displayed;
CC Name=1B;
CC IsoId=P49407-2; Sequence=VSP_000322;
CC -!- DOMAIN: The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction
CC the AP-2 complex subunit AP2B1 (By similarity). Binding to
CC phosphorylated GPCRs induces a conformationanl change that exposes the
CC motif to the surface. {ECO:0000250}.
CC -!- DOMAIN: The N-terminus binds InsP6 with low affinity. {ECO:0000250}.
CC -!- DOMAIN: The C-terminus binds InsP6 with high affinity. {ECO:0000250}.
CC -!- PTM: Constitutively phosphorylated at Ser-412 in the cytoplasm. At the
CC plasma membrane, is rapidly dephosphorylated, a process that is
CC required for clathrin binding and ADRB2 endocytosis but not for ADRB2
CC binding and desensitization. Once internalized, is rephosphorylated.
CC {ECO:0000269|PubMed:19661922}.
CC -!- PTM: The ubiquitination status appears to regulate the formation and
CC trafficking of beta-arrestin-GPCR complexes and signaling.
CC Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2;
CC the ubiquitination is required for rapid internalization of ADRB2.
CC Deubiquitinated by USP33; the deubiquitination leads to a dissociation
CC of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such
CC as ADRB2, induces transient ubiquitination and subsequently promotes
CC association with USP33. {ECO:0000269|PubMed:19363159}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Arrestin entry;
CC URL="https://en.wikipedia.org/wiki/Arrestin";
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DR EMBL; L04685; AAA35559.1; -; mRNA.
DR EMBL; L04685; AAA35558.1; -; mRNA.
DR EMBL; AF084040; AAC33295.1; -; mRNA.
DR EMBL; AF084940; AAC34123.1; -; mRNA.
DR EMBL; DQ314865; ABC40724.1; -; Genomic_DNA.
DR EMBL; FJ348262; ACI96306.1; -; mRNA.
DR EMBL; CH471076; EAW74962.1; -; Genomic_DNA.
DR EMBL; BC003636; AAH03636.1; -; mRNA.
DR CCDS; CCDS31640.1; -. [P49407-2]
DR CCDS; CCDS44684.1; -. [P49407-1]
DR PIR; B46682; B46682.
DR RefSeq; NP_004032.2; NM_004041.4. [P49407-1]
DR RefSeq; NP_064647.1; NM_020251.3. [P49407-2]
DR PDB; 2IV8; X-ray; 2.80 A; P/Q=383-402.
DR PDB; 6PWC; EM; 4.90 A; A=1-393.
DR PDB; 6TKO; EM; 3.30 A; B=1-418.
DR PDB; 6UP7; EM; 4.20 A; B=8-355.
DR PDBsum; 2IV8; -.
DR PDBsum; 6PWC; -.
DR PDBsum; 6TKO; -.
DR PDBsum; 6UP7; -.
DR AlphaFoldDB; P49407; -.
DR SMR; P49407; -.
DR BioGRID; 106901; 290.
DR CORUM; P49407; -.
DR DIP; DIP-29979N; -.
DR ELM; P49407; -.
DR IntAct; P49407; 232.
DR MINT; P49407; -.
DR STRING; 9606.ENSP00000409581; -.
DR BindingDB; P49407; -.
DR ChEMBL; CHEMBL1795088; -.
DR MoonDB; P49407; Curated.
DR MoonProt; P49407; -.
DR TCDB; 8.A.136.1.1; the beta-arrestin (arrb) family.
DR GlyGen; P49407; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49407; -.
DR PhosphoSitePlus; P49407; -.
DR BioMuta; ARRB1; -.
DR DMDM; 20141238; -.
DR OGP; P49407; -.
DR EPD; P49407; -.
DR jPOST; P49407; -.
DR MassIVE; P49407; -.
DR MaxQB; P49407; -.
DR PaxDb; P49407; -.
DR PeptideAtlas; P49407; -.
DR PRIDE; P49407; -.
DR ProteomicsDB; 56001; -. [P49407-1]
DR ProteomicsDB; 56002; -. [P49407-2]
DR Antibodypedia; 3527; 734 antibodies from 43 providers.
DR DNASU; 408; -.
DR Ensembl; ENST00000360025.7; ENSP00000353124.3; ENSG00000137486.17. [P49407-2]
DR Ensembl; ENST00000420843.7; ENSP00000409581.2; ENSG00000137486.17. [P49407-1]
DR GeneID; 408; -.
DR KEGG; hsa:408; -.
DR MANE-Select; ENST00000420843.7; ENSP00000409581.2; NM_004041.5; NP_004032.2.
DR UCSC; uc001owe.3; human. [P49407-1]
DR CTD; 408; -.
DR DisGeNET; 408; -.
DR GeneCards; ARRB1; -.
DR HGNC; HGNC:711; ARRB1.
DR HPA; ENSG00000137486; Low tissue specificity.
DR MIM; 107940; gene.
DR neXtProt; NX_P49407; -.
DR OpenTargets; ENSG00000137486; -.
DR PharmGKB; PA59; -.
DR VEuPathDB; HostDB:ENSG00000137486; -.
DR eggNOG; KOG3865; Eukaryota.
DR GeneTree; ENSGT00950000182887; -.
DR HOGENOM; CLU_033484_1_1_1; -.
DR InParanoid; P49407; -.
DR OMA; LYLAHEQ; -.
DR OrthoDB; 783081at2759; -.
DR PhylomeDB; P49407; -.
DR TreeFam; TF314260; -.
DR PathwayCommons; P49407; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-HSA-5635838; Activation of SMO.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; P49407; -.
DR SIGNOR; P49407; -.
DR BioGRID-ORCS; 408; 198 hits in 1081 CRISPR screens.
DR ChiTaRS; ARRB1; human.
DR EvolutionaryTrace; P49407; -.
DR GeneWiki; Arrestin_beta_1; -.
DR GenomeRNAi; 408; -.
DR Pharos; P49407; Tbio.
DR PRO; PR:P49407; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P49407; protein.
DR Bgee; ENSG00000137486; Expressed in monocyte and 167 other tissues.
DR ExpressionAtlas; P49407; baseline and differential.
DR Genevisible; P49407; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0031143; C:pseudopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0031701; F:angiotensin receptor binding; IPI:UniProtKB.
DR GO; GO:1990763; F:arrestin family protein binding; IPI:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; TAS:ProtInc.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:BHF-UCL.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; IMP:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IMP:BHF-UCL.
DR GO; GO:0090240; P:positive regulation of histone H4 acetylation; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:UniProtKB.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0043149; P:stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR Gene3D; 2.60.40.640; -; 1.
DR Gene3D; 2.60.40.840; -; 1.
DR InterPro; IPR000698; Arrestin.
DR InterPro; IPR014752; Arrestin-like_C.
DR InterPro; IPR011021; Arrestin-like_N.
DR InterPro; IPR011022; Arrestin_C-like.
DR InterPro; IPR017864; Arrestin_CS.
DR InterPro; IPR014753; Arrestin_N.
DR InterPro; IPR014756; Ig_E-set.
DR PANTHER; PTHR11792; PTHR11792; 1.
DR Pfam; PF02752; Arrestin_C; 1.
DR Pfam; PF00339; Arrestin_N; 1.
DR PRINTS; PR00309; ARRESTIN.
DR SMART; SM01017; Arrestin_C; 1.
DR SUPFAM; SSF81296; SSF81296; 2.
DR PROSITE; PS00295; ARRESTINS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Coated pit; Cytoplasm; Cytoplasmic vesicle; Membrane; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome;
KW Signal transduction inhibitor; Transcription; Transcription regulation;
KW Transport; Ubl conjugation.
FT CHAIN 1..418
FT /note="Beta-arrestin-1"
FT /id="PRO_0000205194"
FT REGION 1..163
FT /note="Interaction with SRC"
FT /evidence="ECO:0000250"
FT REGION 45..86
FT /note="Interaction with CHRM2"
FT /evidence="ECO:0000250"
FT REGION 318..418
FT /note="Interaction with TRAF6"
FT /evidence="ECO:0000269|PubMed:16378096"
FT REGION 353..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 385..395
FT /note="[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif"
FT COMPBIAS 353..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..411
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 250
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 324
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT BINDING 326
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250"
FT MOD_RES 47
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWG8"
FT MOD_RES 412
FT /note="Phosphoserine; by GRK5"
FT /evidence="ECO:0000269|PubMed:19661922,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 334..341
FT /note="Missing (in isoform 1B)"
FT /evidence="ECO:0000303|PubMed:8486659, ECO:0000303|Ref.2,
FT ECO:0000303|Ref.4"
FT /id="VSP_000322"
FT MUTAGEN 169
FT /note="R->E: Constitutive active; enables phosphorylation-
FT independent binding to GPCRs."
FT /evidence="ECO:0000269|PubMed:10066734"
FT MUTAGEN 388
FT /note="F->A: Abolishes interaction with AP2B1."
FT /evidence="ECO:0000269|PubMed:16516836"
FT MUTAGEN 390
FT /note="D->P: Abolishes interaction with AP2B1."
FT /evidence="ECO:0000269|PubMed:16516836"
FT MUTAGEN 393
FT /note="R->A: Abolishes interaction with AP2B1."
FT /evidence="ECO:0000269|PubMed:16516836"
FT CONFLICT 146
FT /note="V -> A (in Ref. 1; AAA35559/AAA35558)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="R -> G (in Ref. 1; AAA35559/AAA35558)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="K -> E (in Ref. 1; AAA35559/AAA35558)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="V -> E (in Ref. 2; AAC33295/AAC34123)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="K -> E (in Ref. 1; AAA35559/AAA35558)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="Q -> R (in Ref. 1; AAA35559/AAA35558)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="N -> D (in Ref. 1; AAA35559/AAA35558)"
FT /evidence="ECO:0000305"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 19..23
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 47..62
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 76..87
FT /evidence="ECO:0007829|PDB:6TKO"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:6TKO"
FT HELIX 99..108
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 140..153
FT /evidence="ECO:0007829|PDB:6TKO"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 165..171
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 183..187
FT /evidence="ECO:0007829|PDB:6TKO"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 228..241
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 247..258
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 270..274
FT /evidence="ECO:0007829|PDB:6TKO"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 319..329
FT /evidence="ECO:0007829|PDB:6TKO"
FT STRAND 342..351
FT /evidence="ECO:0007829|PDB:6TKO"
FT HELIX 384..394
FT /evidence="ECO:0007829|PDB:2IV8"
SQ SEQUENCE 418 AA; 47066 MW; 0A3C135092338D10 CRC64;
MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA
FRYGREDLDV LGLTFRKDLF VANVQSFPPA PEDKKPLTRL QERLIKKLGE HAYPFTFEIP
PNLPCSVTLQ PGPEDTGKAC GVDYEVKAFC AENLEEKIHK RNSVRLVIRK VQYAPERPGP
QPTAETTRQF LMSDKPLHLE ASLDKEIYYH GEPISVNVHV TNNTNKTVKK IKISVRQYAD
ICLFNTAQYK CPVAMEEADD TVAPSSTFCK VYTLTPFLAN NREKRGLALD GKLKHEDTNL
ASSTLLREGA NREILGIIVS YKVKVKLVVS RGGLLGDLAS SDVAVELPFT LMHPKPKEEP
PHREVPENET PVDTNLIELD TNDDDIVFED FARQRLKGMK DDKEEEEDGT GSPQLNNR
