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 10-MAY-2017, entry version 166.
DE RecName: Full=Beta-arrestin-1;
DE AltName: Full=Arrestin beta-1;
GN Name=ARRB1; Synonyms=ARR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B).
RC TISSUE=Peripheral blood;
RX PubMed=8486659;
RA Parruti G., Peracchia F., Sallese M., Ambrosini G., Masini M.,
RA Rotilio D., de Blasi A.;
RT "Molecular analysis of human beta-arrestin-1: cloning, tissue
RT distribution, and regulation of expression. Identification of two
RT isoforms generated by 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT desensitization 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
RT mutants 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
RT protein kinase complexes.";
RL Science 283:655-661(1999).
RN [10]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH ANTAGONIST-STIMULATED
RP 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
RT of 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.,
RA Xu L., Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.;
RT "Regulation of tyrosine kinase activation and granule release through
RT beta-arrestin by CXCRI.";
RL Nat. Immunol. 1:227-233(2000).
RN [12]
RP FUNCTION IN INTERNALIZATION OF C5AR1, SUBCELLULAR LOCATION, AND
RP INTERACTION 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
RT internalization of the complement 5a (C5a) anaphylatoxin receptor via
RT a beta-arrestin, 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
RP 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
RT the insulin-like growth factor-1 receptor by acting as adaptor for the
RT MDM2 E3 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,
RP AND 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.,
RA Wang F., 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
RT fiber formation following receptor stimulation.";
RL J. Biol. Chem. 280:8041-8050(2005).
RN [17]
RP FUNCTION IN 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-
RT 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.,
RA Morris D.R., Trejo J.;
RT "Multiple independent functions of arrestins in the regulation of
RT protease-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
RT beta-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
RP 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
RT endocytic 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.,
RA Madabushi S., Reiter E., Premont R.T., Lichtarge O., Lefkowitz R.J.;
RT "beta-arrestin-dependent, G protein-independent ERK1/2 activation by
RT the 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.,
RA Lefkowitz R.J.;
RT "Distinct beta-arrestin- and G protein-dependent pathways for
RT parathyroid 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
RP SIGNALING PATHWAY, FUNCTION IN ACTIN BUNDLE FORMATION, SUBCELLULAR
RP LOCATION, AND 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.,
RA Hamiel C., Sheppard F.R., Moore E.E., Silliman C.C.;
RT "Platelet-activating factor-induced clathrin-mediated endocytosis
RT requires beta-arrestin-1 recruitment and activation of the p38 MAPK
RT signalosome at 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.,
RA 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.,
RA Wiseman P.W., 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
RT signaling 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
RT 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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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.,
RA Reiter E., Baneres J.L., Benovic J.L., Marin P., Bockaert J.,
RA Dumuis A.;
RT "Beta-arrestin1 phosphorylation by GRK5 regulates G protein-
RT independent 5-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
RT the 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.,
RA 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
RT the E3 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
RP BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome 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
RT human chemokine decoy receptor CCX-CKR.";
RL J. Biol. Chem. 288:7169-7181(2013).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION
RP BY 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 [41]
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.,
RA Bonecchi R., Locati M.;
RT "Beta-arrestin-dependent activation of the cofilin pathway is required
RT for the scavenging activity of the atypical chemokine receptor D6.";
RL Sci. Signal. 6:RA30-RA30(2013).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION
RP BY 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.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 383-402 IN COMPLEX WITH
RP 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
RT clathrin-coated vesicle assembly.";
RL PLoS Biol. 4:E262-E262(2006).
CC -!- FUNCTION: Functions in regulating agonist-mediated G-protein
CC coupled receptor (GPCR) signaling by mediating both receptor
CC desensitization and resensitization processes. During homologous
CC desensitization, beta-arrestins bind to the GPRK-phosphorylated
CC receptor and sterically preclude its coupling to the cognate G-
CC protein; the binding appears to require additional receptor
CC determinants exposed only in the active receptor conformation. The
CC beta-arrestins target many receptors for internalization by acting
CC as endocytic adapters (CLASPs, clathrin-associated sorting
CC proteins) and recruiting the GPRCs to the adapter protein 2
CC 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,
CC where they remain uncoupled from G-proteins. Two different modes
CC of arrestin-mediated internalization occur. Class A receptors,
CC like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-
CC arrestin at or near the plasma membrane and undergo rapid
CC recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and
CC TACR1 internalize as a complex with arrestin and traffic with it
CC to endosomal vesicles, presumably as desensitized receptors, for
CC extended periods of time. Receptor resensitization then requires
CC that receptor-bound arrestin is removed so that the receptor can
CC be dephosphorylated and returned to the plasma membrane. Involved
CC in internalization of P2RY4 and UTP-stimulated internalization of
CC P2RY2. Involved in phosphorylation-dependent internalization of
CC OPRD1 ands subsequent recycling. Involved in the degradation of
CC cAMP by recruiting cAMP phosphodiesterases to ligand-activated
CC receptors. Beta-arrestins function as multivalent adapter proteins
CC 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
CC intracellular compartment. Acts as signaling scaffold for MAPK
CC pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-
CC arrestin scaffold is largely excluded from the nucleus and
CC confined to cytoplasmic locations such as endocytic vesicles, also
CC called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2
CC resulting in ERK activation. GPCRs for which the beta-arrestin-
CC mediated signaling relies on both ARRB1 and ARRB2 (codependent
CC regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the
CC beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2
CC and is inhibited by the other respective beta-arrestin form
CC (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and
CC AVPR2-mediated activation (reciprocal regulation). Is required for
CC SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to
CC internalized NK1R resulting in ERK1/2 activation, which is
CC required for the antiapoptotic effects of SP. Is involved in
CC proteinase-activated F2RL1-mediated ERK activity. Acts as
CC signaling scaffold for the AKT1 pathway. Is involved in alpha-
CC thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated
CC AKT1 signaling leading to increased protection from apoptosis.
CC Involved in activation of the p38 MAPK signaling pathway and in
CC actin bundle formation. Involved in F2RL1-mediated cytoskeletal
CC rearrangement and chemotaxis. Involved in AGTR1-mediated stress
CC fiber formation by acting together with GNAQ to activate RHOA.
CC Appears to function as signaling scaffold involved in regulation
CC of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in
CC attenuation of NF-kappa-B-dependent transcription in response to
CC GPCR or cytokine stimulation by interacting with and stabilizing
CC CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1-
CC stimulated transcriptional regulation by translocating to CDKN1B
CC and FOS promoter regions and recruiting EP300 resulting in
CC acetylation of histone H4. Involved in regulation of LEF1
CC transcriptional activity via interaction with DVL1 and/or DVL2
CC Also involved in regulation of receptors other than GPCRs.
CC Involved in Toll-like receptor and IL-1 receptor signaling through
CC the interaction with TRAF6 which prevents TRAF6 autoubiquitination
CC and oligomerization required for activation of NF-kappa-B and JUN.
CC Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6)
CC (By similarity). Involved in IL8-mediated granule release in
CC neutrophils. Required for atypical chemokine receptor ACKR2-
CC induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin
CC (CFL1) and for the up-regulation of ACKR2 from endosomal
CC compartment to cell membrane, increasing its efficiency in
CC chemokine uptake and degradation. Involved in the internalization
CC of the atypical chemokine receptor ACKR3. {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 -!- SUBUNIT: Monomer. Homodimer. Homooligomer; the self-association is
CC mediated by InsP6-binding. Heterooligomer with ARRB2; the
CC association is mediated by InsP6-binding. Interacts with GPR143.
CC Interacts with ADRB2 (phosphorylated). Interacts with CHRM2
CC (phosphorylated). Interacts with LHCGR. Interacts with CYTH2 and
CC CASR. Interacts with AP2B1 (dephosphorylated at 'Tyr-737');
CC phosphorylation of AP2B1 at 'Tyr-737' disrupts the interaction.
CC Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with
CC CCR2 and GRK2. Interacts with CRR5. Interacts with PTAFR
CC (phosphorylated on serine residues). Interacts with CLTC and
CC MAP2K3. Interacts with CREB1. Interacts with TRAF6. Interacts with
CC IGF1R and MDM2. Interacts with C5AR1. Interacts with PDE4D.
CC Interacts with SRC (via the SH3 domain and the protein kinase
CC domain); the interaction is independent of the phosphorylation
CC state of SRC C-terminus. Interacts with TACR1. Interacts with
CC RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts with DVL1;
CC the interaction is enhanced by phosphorylation of DVL1. Interacts
CC with DVL2; the interaction is enhanced by phosphorylation of DVL2.
CC Interacts with IGF1R. Associates with MAP kinase p38. Part of a
CC MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1
CC (activated) and MAPK3 (activated). Part of a MAPK signaling
CC complex consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and
CC MAPK3 (activated) (By similarity). Interacts with MAP2K4/MKK4.
CC Interacts with HCK and CXCR1 (phosphorylated). Interacts with
CC ACKR3 and ACKR4. {ECO:0000250, ECO:0000269|PubMed:10973280,
CC ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:15878855,
CC ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16325578,
CC ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16516836,
CC ECO:0000269|PubMed:16524428, ECO:0000269|PubMed:16709866,
CC ECO:0000269|PubMed:16903783, ECO:0000269|PubMed:17456551,
CC ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:19782076,
CC ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23341447,
CC ECO:0000269|PubMed:9501202, ECO:0000269|PubMed:9924018}.
CC -!- INTERACTION:
CC P62158:CALM3; NbExp=3; IntAct=EBI-743313, EBI-397435;
CC P20963:CD247; NbExp=9; IntAct=EBI-743313, EBI-1165705;
CC P50148:GNAQ; NbExp=2; IntAct=EBI-743313, EBI-3909604;
CC Q5JWF2:GNAS; NbExp=5; IntAct=EBI-743313, EBI-4400880;
CC Q14749:GNMT; NbExp=7; IntAct=EBI-743313, EBI-744239;
CC P06396:GSN; NbExp=3; IntAct=EBI-743313, EBI-351506;
CC Q16665:HIF1A; NbExp=3; IntAct=EBI-743313, EBI-447269;
CC P11142:HSPA8; NbExp=4; IntAct=EBI-743313, EBI-351896;
CC Q99683:MAP3K5; NbExp=3; IntAct=EBI-743313, EBI-476263;
CC P53779:MAPK10; NbExp=2; IntAct=EBI-743313, EBI-713543;
CC P45984:MAPK9; NbExp=7; IntAct=EBI-743313, EBI-713568;
CC P19338:NCL; NbExp=3; IntAct=EBI-743313, EBI-346967;
CC Q14978:NOLC1; NbExp=3; IntAct=EBI-743313, EBI-396155;
CC P14618:PKM; NbExp=3; IntAct=EBI-743313, EBI-353408;
CC P35813:PPM1A; NbExp=4; IntAct=EBI-743313, EBI-989143;
CC O75688:PPM1B; NbExp=4; IntAct=EBI-743313, EBI-1047039;
CC Q13523:PRPF4B; NbExp=2; IntAct=EBI-743313, EBI-395940;
CC P06702:S100A9; NbExp=2; IntAct=EBI-743313, EBI-1055001;
CC Q15208:STK38; NbExp=3; IntAct=EBI-743313, EBI-458376;
CC Q13428:TCOF1; NbExp=3; IntAct=EBI-743313, EBI-396105;
CC Q7DB77:tir (xeno); NbExp=3; IntAct=EBI-743313, EBI-6480811;
CC P27348:YWHAQ; NbExp=3; IntAct=EBI-743313, EBI-359854;
CC P25490:YY1; NbExp=4; IntAct=EBI-743313, EBI-765538;
CC O43298:ZBTB43; NbExp=3; IntAct=EBI-743313, EBI-740718;
CC O95218:ZRANB2; NbExp=4; IntAct=EBI-743313, EBI-1051583;
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
CC plasma membrane and colocalizes with antagonist-stimulated GPCRs.
CC The monomeric form is predominantly located in the nucleus. The
CC oligomeric form is located in the cytoplasm. Translocates to the
CC nucleus upon 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
CC interaction the AP-2 complex subunit AP2B1 (By similarity).
CC Binding to phosphorylated GPCRs induces a conformationanl change
CC that exposes the motif to the surface. {ECO:0000250}.
CC -!- DOMAIN: The N-terminus binds InsP6 with low affinity.
CC {ECO:0000250}.
CC -!- DOMAIN: The C-terminus binds InsP6 with high affinity.
CC {ECO:0000250}.
CC -!- PTM: Constitutively phosphorylated at Ser-412 in the cytoplasm. At
CC the plasma membrane, is rapidly dephosphorylated, a process that
CC is required for clathrin binding and ADRB2 endocytosis but not for
CC ADRB2 binding and desensitization. Once internalized, is
CC rephosphorylated. {ECO:0000269|PubMed:19661922}.
CC -!- PTM: The ubiquitination status appears to regulate the formation
CC and trafficking of beta-arrestin-GPCR complexes and signaling.
CC Ubiquitination appears to occur GPCR-specific. Ubiquitinated by
CC MDM2; the ubiquitination is required for rapid internalization of
CC ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a
CC dissociation of the beta-arrestin-GPCR complex. Stimulation of a
CC class A GPCR, such as ADRB2, induces transient ubiquitination and
CC subsequently promotes association with USP33.
CC {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";
CC -----------------------------------------------------------------------
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CC -----------------------------------------------------------------------
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 UniGene; Hs.503284; -.
DR UniGene; Hs.625320; -.
DR PDB; 2IV8; X-ray; 2.80 A; P/Q=383-402.
DR PDBsum; 2IV8; -.
DR ProteinModelPortal; P49407; -.
DR SMR; P49407; -.
DR BioGrid; 106901; 255.
DR DIP; DIP-29979N; -.
DR IntAct; P49407; 212.
DR MINT; MINT-128176; -.
DR STRING; 9606.ENSP00000409581; -.
DR BindingDB; P49407; -.
DR ChEMBL; CHEMBL1795088; -.
DR iPTMnet; P49407; -.
DR PhosphoSitePlus; P49407; -.
DR BioMuta; ARRB1; -.
DR DMDM; 20141238; -.
DR OGP; P49407; -.
DR EPD; P49407; -.
DR MaxQB; P49407; -.
DR PaxDb; P49407; -.
DR PeptideAtlas; P49407; -.
DR PRIDE; P49407; -.
DR DNASU; 408; -.
DR Ensembl; ENST00000360025; ENSP00000353124; ENSG00000137486. [P49407-2]
DR Ensembl; ENST00000420843; ENSP00000409581; ENSG00000137486. [P49407-1]
DR GeneID; 408; -.
DR KEGG; hsa:408; -.
DR UCSC; uc001owe.3; human. [P49407-1]
DR CTD; 408; -.
DR DisGeNET; 408; -.
DR GeneCards; ARRB1; -.
DR HGNC; HGNC:711; ARRB1.
DR HPA; CAB003763; -.
DR HPA; HPA049318; -.
DR MIM; 107940; gene.
DR neXtProt; NX_P49407; -.
DR OpenTargets; ENSG00000137486; -.
DR PharmGKB; PA59; -.
DR eggNOG; KOG3865; Eukaryota.
DR eggNOG; ENOG410XR0F; LUCA.
DR GeneTree; ENSGT00390000013152; -.
DR HOGENOM; HOG000231319; -.
DR HOVERGEN; HBG002399; -.
DR InParanoid; P49407; -.
DR KO; K04439; -.
DR OMA; LMHPKPL; -.
DR OrthoDB; EOG091G05M2; -.
DR PhylomeDB; P49407; -.
DR TreeFam; TF314260; -.
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-6802949; Signaling by RAS mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF 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 SignaLink; P49407; -.
DR SIGNOR; P49407; -.
DR ChiTaRS; ARRB1; human.
DR EvolutionaryTrace; P49407; -.
DR GeneWiki; Arrestin_beta_1; -.
DR GenomeRNAi; 408; -.
DR PRO; PR:P49407; -.
DR Proteomes; UP000005640; Chromosome 11.
DR Bgee; ENSG00000137486; -.
DR CleanEx; HS_ARRB1; -.
DR ExpressionAtlas; P49407; baseline and differential.
DR Genevisible; P49407; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
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; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
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; TAS:ProtInc.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0031143; C:pseudopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0031691; F:alpha-1A adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0031701; F:angiotensin receptor binding; IPI:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IEA:Ensembl.
DR GO; GO:0035615; F:clathrin adaptor activity; IEA:Ensembl.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0004857; F:enzyme inhibitor activity; TAS:ProtInc.
DR GO; GO:0030331; F:estrogen receptor binding; IEA:Ensembl.
DR GO; GO:0031762; F:follicle-stimulating hormone receptor binding; IEA:Ensembl.
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:0044325; F:ion channel binding; IEA:Ensembl.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IEA:Ensembl.
DR GO; GO:0045309; F:protein phosphorylated amino acid binding; IEA:Ensembl.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IMP:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0031896; F:V2 vasopressin receptor binding; IEA:Ensembl.
DR GO; GO:0000187; P:activation of MAPK activity; IEA:Ensembl.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IEA:Ensembl.
DR GO; GO:0002031; P:G-protein coupled receptor internalization; IMP:UniProtKB.
DR GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl.
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:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0007602; P:phototransduction; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
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:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
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:0034393; P:positive regulation of smooth muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; 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:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0043149; P:stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR Gene3D; 2.60.40.840; -; 1.
DR InterPro; IPR000698; Arrestin.
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; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Membrane; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Signal transduction inhibitor; Transcription;
KW Transcription regulation; Transport; Ubl conjugation.
FT CHAIN 1 418 Beta-arrestin-1.
FT /FTId=PRO_0000205194.
FT REGION 1 163 Interaction with SRC. {ECO:0000250}.
FT REGION 45 86 Interaction with CHRM2. {ECO:0000250}.
FT REGION 318 418 Interaction with TRAF6.
FT {ECO:0000269|PubMed:16378096}.
FT MOTIF 385 395 [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif.
FT BINDING 250 250 Inositol hexakisphosphate. {ECO:0000250}.
FT BINDING 255 255 Inositol hexakisphosphate. {ECO:0000250}.
FT BINDING 324 324 Inositol hexakisphosphate. {ECO:0000250}.
FT BINDING 326 326 Inositol hexakisphosphate. {ECO:0000250}.
FT MOD_RES 47 47 Phosphotyrosine.
FT {ECO:0000250|UniProtKB:Q8BWG8}.
FT MOD_RES 412 412 Phosphoserine; by GRK5.
FT {ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:23186163,
FT ECO:0000244|PubMed:24275569,
FT ECO:0000269|PubMed:19661922}.
FT VAR_SEQ 334 341 Missing (in isoform 1B).
FT {ECO:0000303|PubMed:8486659,
FT ECO:0000303|Ref.2, ECO:0000303|Ref.4}.
FT /FTId=VSP_000322.
FT MUTAGEN 169 169 R->E: Constitutive active; enables
FT phosphorylation-independent binding to
FT GPCRs. {ECO:0000269|PubMed:10066734}.
FT MUTAGEN 388 388 F->A: Abolishes interaction with AP2B1.
FT {ECO:0000269|PubMed:16516836}.
FT MUTAGEN 390 390 D->P: Abolishes interaction with AP2B1.
FT {ECO:0000269|PubMed:16516836}.
FT MUTAGEN 393 393 R->A: Abolishes interaction with AP2B1.
FT {ECO:0000269|PubMed:16516836}.
FT CONFLICT 146 146 V -> A (in Ref. 1; AAA35559/AAA35558).
FT {ECO:0000305}.
FT CONFLICT 165 165 R -> G (in Ref. 1; AAA35559/AAA35558).
FT {ECO:0000305}.
FT CONFLICT 229 229 K -> E (in Ref. 1; AAA35559/AAA35558).
FT {ECO:0000305}.
FT CONFLICT 329 329 V -> E (in Ref. 2; AAC33295/AAC34123).
FT {ECO:0000305}.
FT CONFLICT 400 400 K -> E (in Ref. 1; AAA35559/AAA35558).
FT {ECO:0000305}.
FT CONFLICT 414 414 Q -> R (in Ref. 1; AAA35559/AAA35558).
FT {ECO:0000305}.
FT CONFLICT 417 417 N -> D (in Ref. 1; AAA35559/AAA35558).
FT {ECO:0000305}.
FT HELIX 384 394 {ECO:0000244|PDB:2IV8}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 61 79 ipat:ARRESTINS [T]
FT MYHIT 194 355 ipfam:Arrestin_C [T]
FT MYHIT 193 356 ismart:Arrestin_C [T]
FT MYHIT 19 174 ipfam:Arrestin_N [T]
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
//
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