ARRB1_RAT
ID ARRB1_RAT Reviewed; 418 AA.
AC P29066;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Beta-arrestin-1;
DE AltName: Full=Arrestin beta-1;
GN Name=Arrb1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1517224; DOI=10.1016/s0021-9258(19)37125-x;
RA Attramadal H., Arriza J.L., Aoki C., Dawson T.M., Codina J., Kwatra M.M.,
RA Snyder S.H., Caron M.G., Lefkowitz R.J.;
RT "Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene
RT family.";
RL J. Biol. Chem. 267:17882-17890(1992).
RN [2]
RP FUNCTION IN INTERNALIZATION OF ADRB2, AND MUTAGENESIS OF VAL-53.
RX PubMed=8553074; DOI=10.1126/science.271.5247.363;
RA Ferguson S.S.G., Downey W.E. III, Colapietro A.-M., Barak L.S., Menard L.,
RA Caron M.G.;
RT "Role of beta-arrestin in mediating agonist-promoted G protein-coupled
RT receptor internalization.";
RL Science 271:363-366(1996).
RN [3]
RP FUNCTION IN DESENSITIZATION, FUNCTION IN INTERNALIZATION OF ADBR2,
RP PHOSPHORYLATION AT SER-412, INTERACTION WITH ADRB2 AND CLTC, AND
RP MUTAGENESIS OF SER-412.
RX PubMed=9388255; DOI=10.1074/jbc.272.49.31051;
RA Lin F.-T., Krueger K.M., Kendall H.E., Daaka Y., Fredericks Z.L.,
RA Pitcher J.A., Lefkowitz R.J.;
RT "Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated
RT by phosphorylation/dephosphorylation of beta-arrestin1.";
RL J. Biol. Chem. 272:31051-31057(1997).
RN [4]
RP FUNCTION IN INTERNALIZATION OF IGFR1, FUNCTION IN MAPK SIGNALING,
RP INTERACTION WITH IGF1R, AND MUTAGENESIS OF SER-412.
RX PubMed=9822622; DOI=10.1074/jbc.273.48.31640;
RA Lin F.-T., Daaka Y., Lefkowitz R.J.;
RT "beta-arrestins regulate mitogenic signaling and clathrin-mediated
RT endocytosis of the insulin-like growth factor I receptor.";
RL J. Biol. Chem. 273:31640-31643(1998).
RN [5]
RP FUNCTION IN INTERNALIZATION OF CHRM1; CHRM3 AND CHRM4.
RX PubMed=10212203; DOI=10.1074/jbc.274.18.12333;
RA Voegler O., Nolte B., Voss M., Schmidt M., Jakobs K.H., van Koppen C.J.;
RT "Regulation of muscarinic acetylcholine receptor sequestration and function
RT by beta-arrestin.";
RL J. Biol. Chem. 274:12333-12338(1999).
RN [6]
RP FUNCTION IN INTERNALIZATION OF IL8RA, AND SUBCELLULAR LOCATION.
RX PubMed=10347185; DOI=10.1074/jbc.274.23.16287;
RA Barlic J., Khandaker M.H., Mahon E., Andrews J., DeVries M.E.,
RA Mitchell G.B., Rahimpour R., Tan C.M., Ferguson S.S.G., Kelvin D.J.;
RT "beta-arrestins regulate interleukin-8-induced CXCR1 internalization.";
RL J. Biol. Chem. 274:16287-16294(1999).
RN [7]
RP INTERACTION WITH AP2B1, AND SUBCELLULAR LOCATION.
RX PubMed=10097102; DOI=10.1073/pnas.96.7.3712;
RA Laporte S.A., Oakley R.H., Zhang J., Holt J.A., Ferguson S.S.G.,
RA Caron M.G., Barak L.S.;
RT "The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin
RT adaptor AP-2 during endocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3712-3717(1999).
RN [8]
RP FUNCTION IN MAPK SIGNALING, SUBCELLULAR LOCATION, INTERACTION WITH SRC, AND
RP MUTAGENESIS OF VAL-53; PRO-91; PRO-121 AND SER-412.
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 [9]
RP INTERACTION WITH SRC.
RX PubMed=10753943; DOI=10.1074/jbc.275.15.11312;
RA Miller W.E., Maudsley S., Ahn S., Khan K.D., Luttrell L.M., Lefkowitz R.J.;
RT "beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase
RT c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor
RT endocytosis.";
RL J. Biol. Chem. 275:11312-11319(2000).
RN [10]
RP FUNCTION IN INTERNALIZATION OF EDNRA AND EDNRB, AND MUTAGENESIS OF VAL-53.
RX PubMed=10747877; DOI=10.1074/jbc.m000142200;
RA Bremnes T., Paasche J.D., Mehlum A., Sandberg C., Bremnes B.,
RA Attramadal H.;
RT "Regulation and intracellular trafficking pathways of the endothelin
RT receptors.";
RL J. Biol. Chem. 275:17596-17604(2000).
RN [11]
RP INTERACTION WITH AP2B1 AND CLTC, AND SUBCELLULAR LOCATION.
RX PubMed=10770944; DOI=10.1074/jbc.m002581200;
RA Laporte S.A., Oakley R.H., Holt J.A., Barak L.S., Caron M.G.;
RT "The interaction of beta-arrestin with the AP-2 adaptor is required for the
RT clustering of beta 2-adrenergic receptor into clathrin-coated pits.";
RL J. Biol. Chem. 275:23120-23126(2000).
RN [12]
RP FUNCTION IN MAPK SIGNALING, INTERACTION WITH RAF1, SUBCELLULAR LOCATION,
RP AND IDENTIFICATION IN A COMPLEX WITH F2RL1; MAPK1; MAPK3 AND RAF1.
RX PubMed=10725339; DOI=10.1083/jcb.148.6.1267;
RA DeFea K.A., Zalevsky J., Thoma M.S., Dery O., Mullins R.D., Bunnett N.W.;
RT "beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is
RT required for intracellular targeting of activated ERK1/2.";
RL J. Cell Biol. 148:1267-1281(2000).
RN [13]
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 [14]
RP FUNCTION IN MAPK SIGNALING, SUBCELLULAR LOCATION, INTERACTION WITH SRC AND
RP TACR1, AND IDENTIFICATION IN A COMPLEX WITH SRC; MAPK1; MAPK3 AND TACR1.
RX PubMed=10995467; DOI=10.1073/pnas.190276697;
RA DeFea K.A., Vaughn Z.D., O'Bryan E.M., Nishijima D., Dery O., Bunnett N.W.;
RT "The proliferative and antiapoptotic effects of substance P are facilitated
RT by formation of a beta -arrestin-dependent scaffolding complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:11086-11091(2000).
RN [15]
RP FUNCTION IN TRANSCRIPTIONAL REGULATION, AND INTERACTION WITH DVL1 AND DVL2.
RX PubMed=11742073; DOI=10.1073/pnas.211572798;
RA Chen W., Hu L.A., Semenov M.V., Yanagawa S., Kikuchi A., Lefkowitz R.J.,
RA Miller W.E.;
RT "beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity
RT through interaction with phosphorylated dishevelled proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14889-14894(2001).
RN [16]
RP FUNCTION INTERNALIZATION OF AGTR1, AND INTERACTION WITH AGTR1.
RX PubMed=11579203; DOI=10.1210/mend.15.10.0714;
RA Qian H., Pipolo L., Thomas W.G.;
RT "Association of beta-Arrestin 1 with the type 1A angiotensin II receptor
RT involves phosphorylation of the receptor carboxyl terminus and correlates
RT with receptor internalization.";
RL Mol. Endocrinol. 15:1706-1719(2001).
RN [17]
RP INTERACTION WITH AP2B1.
RX PubMed=11777907; DOI=10.1074/jbc.m108490200;
RA Laporte S.A., Miller W.E., Kim K.-M., Caron M.G.;
RT "beta-Arrestin/AP-2 interaction in G protein-coupled receptor
RT internalization: identification of a beta-arrestin binding site in beta 2-
RT adaptin.";
RL J. Biol. Chem. 277:9247-9254(2002).
RN [18]
RP FUNCTION IN ERK SIGNALING.
RX PubMed=11777902; DOI=10.1074/jbc.m106457200;
RA Tohgo A., Pierce K.L., Choy E.W., Lefkowitz R.J., Luttrell L.M.;
RT "beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK
RT activity but inhibits ERK-mediated transcription following angiotensin AT1a
RT receptor stimulation.";
RL J. Biol. Chem. 277:9429-9436(2002).
RN [19]
RP FUNCTION IN AKT1 SIGNALING.
RX PubMed=11901145; DOI=10.1074/jbc.m108995200;
RA Goel R., Phillips-Mason P.J., Raben D.M., Baldassare J.J.;
RT "alpha-Thrombin induces rapid and sustained Akt phosphorylation by beta-
RT arrestin1-dependent and -independent mechanisms, and only the sustained Akt
RT phosphorylation is essential for G1 phase progression.";
RL J. Biol. Chem. 277:18640-18648(2002).
RN [20]
RP FUNCTION IN CAMP DEGRADATION, AND INTERACTION WITH PDE4D.
RX PubMed=12399592; DOI=10.1126/science.1074683;
RA Perry S.J., Baillie G.S., Kohout T.A., McPhee I., Magiera M.M., Ang K.L.,
RA Miller W.E., McLean A.J., Conti M., Houslay M.D., Lefkowitz R.J.;
RT "Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by
RT beta-arrestins.";
RL Science 298:834-836(2002).
RN [21]
RP FUNCTION IN INTERNALIZATION OF GRM1.
RX PubMed=12519791; DOI=10.1074/jbc.m203992200;
RA Iacovelli L., Salvatore L., Capobianco L., Picascia A., Barletta E.,
RA Storto M., Mariggio S., Sallese M., Porcellini A., Nicoletti F.,
RA De Blasi A.;
RT "Role of G protein-coupled receptor kinase 4 and beta-arrestin 1 in
RT agonist-stimulated metabotropic glutamate receptor 1 internalization and
RT activation of mitogen-activated protein kinases.";
RL J. Biol. Chem. 278:12433-12442(2003).
RN [22]
RP FUNCTION IN CYTOSKELETAL REARRANGEMENT AND CHEMOTAXIS, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12821670; DOI=10.1074/jbc.m300573200;
RA Ge L., Ly Y., Hollenberg M., DeFea K.;
RT "A beta-arrestin-dependent scaffold is associated with prolonged MAPK
RT activation in pseudopodia during protease-activated receptor-2-induced
RT chemotaxis.";
RL J. Biol. Chem. 278:34418-34426(2003).
RN [23]
RP FUNCTION IN REGULATION OF NF-KAPPA-B, AND INTERACTION WITH CHUK; IKBKB AND
RP MAP3K14.
RX PubMed=15173580; DOI=10.1073/pnas.0402851101;
RA Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J.;
RT "beta-Arrestin inhibits NF-kappaB activity by means of its interaction with
RT the NF-kappaB inhibitor IkappaBalpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004).
RN [24]
RP FUNCTION IN UBIQUITINATION OF IGF1R.
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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [26]
RP FUNCTION IN INTERNALIZATION OF FPR1.
RX PubMed=17594911; DOI=10.1016/j.cellsig.2007.05.006;
RA Huet E., Boulay F., Barral S., Rabiet M.J.;
RT "The role of beta-arrestins in the formyl peptide receptor-like 1
RT internalization and signaling.";
RL Cell. Signal. 19:1939-1948(2007).
RN [27]
RP FUNCTION IN DESENSITIZATION OF AGTR1.
RX PubMed=18006496; DOI=10.1074/jbc.m706892200;
RA Lee M.-H., El-Shewy H.M., Luttrell D.K., Luttrell L.M.;
RT "Role of beta-arrestin-mediated desensitization and signaling in the
RT control of angiotensin AT1a receptor-stimulated transcription.";
RL J. Biol. Chem. 283:2088-2097(2008).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [29]
RP 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).
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 (By similarity). Negatively
CC regulates the NOTCH signaling pathway by mediating the ubiquitination
CC and degradation of NOTCH1 by ITCH. Participates in the recruitment of
CC the ubiquitin-protein ligase to the receptor (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P49407,
CC ECO:0000269|PubMed:10212203, ECO:0000269|PubMed:10347185,
CC ECO:0000269|PubMed:10725339, ECO:0000269|PubMed:10747877,
CC ECO:0000269|PubMed:10995467, ECO:0000269|PubMed:11579203,
CC ECO:0000269|PubMed:11742073, ECO:0000269|PubMed:11777902,
CC ECO:0000269|PubMed:11901145, ECO:0000269|PubMed:12399592,
CC ECO:0000269|PubMed:12519791, ECO:0000269|PubMed:12821670,
CC ECO:0000269|PubMed:15173580, ECO:0000269|PubMed:15878855,
CC ECO:0000269|PubMed:17594911, ECO:0000269|PubMed:18006496,
CC ECO:0000269|PubMed:8553074, ECO:0000269|PubMed:9388255,
CC ECO:0000269|PubMed:9822622, ECO:0000269|PubMed:9924018}.
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 ADRB2 (phosphorylated).
CC Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts
CC with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated at 'Tyr-
CC 737'); phosphorylation of AP2B1 at 'Tyr-737' disrupts the interaction.
CC Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with CCR2
CC and GRK2. Interacts with CRR5. Interacts with PTAFR (phosphorylated on
CC serine residues). Interacts with CLTC and MAP2K3. Interacts with CREB1.
CC Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with
CC C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and
CC the protein kinase domain); the interaction is independent of the
CC phosphorylation state of SRC C-terminus. Interacts with TACR1.
CC Interacts with RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts
CC with DVL1; the interaction is enhanced by phosphorylation of DVL1.
CC Interacts with DVL2; the interaction is enhanced by phosphorylation of
CC DVL2. 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 complex
CC consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3
CC (activated). Interacts with GPR143 (By similarity). Interacts with
CC MAP2K4/MKK4 (By similarity). Interacts with HCK and CXCR1
CC (phosphorylated). Interacts with ACKR3 and ACKR4 (By similarity).
CC Interacts with ARRDC1; the interaction is direct (PubMed:23886940).
CC Interacts with GPR61, GPR62 and GPR135 (By similarity).
CC {ECO:0000250|UniProtKB:P49407, ECO:0000269|PubMed:23886940}.
CC -!- INTERACTION:
CC P29066; P11345: Raf1; NbExp=5; IntAct=EBI-4303019, EBI-931534;
CC P29066; P55085: F2RL1; Xeno; NbExp=6; IntAct=EBI-4303019, EBI-4303189;
CC P29066; P53667: LIMK1; Xeno; NbExp=2; IntAct=EBI-4303019, EBI-444403;
CC P29066; Q96GD0: PDXP; Xeno; NbExp=2; IntAct=EBI-4303019, EBI-4303060;
CC P29066; P04637: TP53; Xeno; NbExp=3; IntAct=EBI-4303019, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane. Membrane,
CC clathrin-coated pit {ECO:0000305}. Cell projection, pseudopodium.
CC Cytoplasmic vesicle. Note=Translocates to the plasma membrane and
CC colocalizes with antagonist-stimulated GPCRs. The monomeric form is
CC predominantly located in the nucleus. The oligomeric form is located in
CC the cytoplasm. Translocates to the nucleus upon stimulation of OPRD1
CC (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Predominantly localized in neuronal tissues and in
CC the spleen.
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. Binding to phosphorylated GPCRs induces
CC a conformationanl change that exposes the motif to the surface (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The N-terminus binds InsP6 with low affinity.
CC -!- DOMAIN: The C-terminus binds InsP6 with high affinity.
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 beta-2 adrenergic receptor/ADRB2
CC endocytosis but not for ADRB2 binding and desensitization. Once
CC internalized, is rephosphorylated. {ECO:0000269|PubMed:9388255}.
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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR EMBL; M91589; AAA74459.1; -; mRNA.
DR PIR; B43404; B43404.
DR RefSeq; NP_037042.1; NM_012910.2.
DR PDB; 4JQI; X-ray; 2.60 A; A=2-393.
DR PDB; 6KL7; X-ray; 2.79 A; A/B=1-418.
DR PDB; 6U1N; EM; 4.00 A; C=2-393.
DR PDBsum; 4JQI; -.
DR PDBsum; 6KL7; -.
DR PDBsum; 6U1N; -.
DR AlphaFoldDB; P29066; -.
DR SMR; P29066; -.
DR BioGRID; 247425; 12.
DR DIP; DIP-40808N; -.
DR IntAct; P29066; 15.
DR MINT; P29066; -.
DR STRING; 10116.ENSRNOP00000046069; -.
DR iPTMnet; P29066; -.
DR PhosphoSitePlus; P29066; -.
DR jPOST; P29066; -.
DR PaxDb; P29066; -.
DR PRIDE; P29066; -.
DR ABCD; P29066; 1 sequenced antibody.
DR GeneID; 25387; -.
DR KEGG; rno:25387; -.
DR CTD; 408; -.
DR RGD; 2156; Arrb1.
DR VEuPathDB; HostDB:ENSRNOG00000030404; -.
DR eggNOG; KOG3865; Eukaryota.
DR HOGENOM; CLU_033484_1_1_1; -.
DR InParanoid; P29066; -.
DR OMA; LYLAHEQ; -.
DR OrthoDB; 783081at2759; -.
DR PhylomeDB; P29066; -.
DR TreeFam; TF314260; -.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR Reactome; R-RNO-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-RNO-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-RNO-5635838; Activation of SMO.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:P29066; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000030404; Expressed in frontal cortex and 18 other tissues.
DR Genevisible; P29066; RN.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD.
DR GO; GO:0031143; C:pseudopodium; ISO:RGD.
DR GO; GO:0031691; F:alpha-1A adrenergic receptor binding; IPI:RGD.
DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; IDA:RGD.
DR GO; GO:0031701; F:angiotensin receptor binding; ISO:RGD.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IDA:BHF-UCL.
DR GO; GO:1990763; F:arrestin family protein binding; IPI:UniProtKB.
DR GO; GO:0035615; F:clathrin adaptor activity; IDA:BHF-UCL.
DR GO; GO:0030276; F:clathrin binding; IDA:RGD.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0031762; F:follicle-stimulating hormone receptor binding; IPI:RGD.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; ISO:RGD.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISO:RGD.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB.
DR GO; GO:0045309; F:protein phosphorylated amino acid binding; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0031896; F:V2 vasopressin receptor binding; IDA:RGD.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; TAS:RGD.
DR GO; GO:0006897; P:endocytosis; IDA:RGD.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IDA:RGD.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:RGD.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:RGD.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0007602; P:phototransduction; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:RGD.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISO:RGD.
DR GO; GO:0090240; P:positive regulation of histone H4 acetylation; ISO:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS:UniProtKB.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISO:RGD.
DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0019233; P:sensory perception of pain; TAS:RGD.
DR GO; GO:0050975; P:sensory perception of touch; TAS:RGD.
DR GO; GO:0043149; P:stress fiber assembly; ISO:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS: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; Cell membrane; Cell projection; Coated pit; Cytoplasm;
KW Cytoplasmic vesicle; Membrane; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Signal transduction inhibitor; Transcription;
KW Transcription regulation; Transport; Ubl conjugation.
FT CHAIN 1..418
FT /note="Beta-arrestin-1"
FT /id="PRO_0000205197"
FT REGION 1..163
FT /note="Interaction with SRC"
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:0000250"
FT REGION 353..374
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 COMPBIAS 353..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..412
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"
FT /evidence="ECO:0000269|PubMed:9388255,
FT ECO:0007744|PubMed:16641100, ECO:0007744|PubMed:22673903"
FT MOD_RES 412
FT /note="Phosphoserine; by GRK5"
FT /evidence="ECO:0000250"
FT MUTAGEN 53
FT /note="V->D: Inhibits internalization of EDNRA, EDNRB and
FT ADRB2. No effect on interaction with SRC; impairs
FT ADRB2- and HTR1A-mediated ERK phosphorylation; impairs
FT sequestration of ADRB2."
FT /evidence="ECO:0000269|PubMed:10747877,
FT ECO:0000269|PubMed:8553074, ECO:0000269|PubMed:9924018"
FT MUTAGEN 91
FT /note="P->G: Impairs interaction with SRC; impairs
FT ADRB2- and HTR1A-mediated ERK phosphorylation; no effect on
FT sequestration of ADRB2; when associated with E-121."
FT /evidence="ECO:0000269|PubMed:9924018"
FT MUTAGEN 121
FT /note="P->E: Impairs interaction with SRC; impairs
FT ADRB2- and HTR1A-mediated ERK phosphorylation; no effect on
FT sequestration of ADRB2; when associated with G-91."
FT /evidence="ECO:0000269|PubMed:9924018"
FT MUTAGEN 412
FT /note="S->A: Abolishes phosphorylation and inhibits ADRB2
FT endocytosis; no effect on interaction with ADRB2."
FT /evidence="ECO:0000269|PubMed:9388255,
FT ECO:0000269|PubMed:9822622, ECO:0000269|PubMed:9924018"
FT MUTAGEN 412
FT /note="S->D: Impairs interaction with SRC; impairs ADRB2-
FT mediated ERK phosphorylation and IGFR1-mediated MAP kinase
FT phosphorylation of GAB1; impairs sequestration of ADRB2 and
FT IGFR1; abolishes interaction with clathrin; no effect on
FT interaction with ADRB2 and IGFR1."
FT /evidence="ECO:0000269|PubMed:9388255,
FT ECO:0000269|PubMed:9822622, ECO:0000269|PubMed:9924018"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:4JQI"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 53..63
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 73..87
FT /evidence="ECO:0007829|PDB:4JQI"
FT HELIX 99..108
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:6KL7"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:6KL7"
FT STRAND 141..150
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:4JQI"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 163..171
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:6KL7"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 214..222
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 228..258
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 266..274
FT /evidence="ECO:0007829|PDB:4JQI"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:6KL7"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 315..329
FT /evidence="ECO:0007829|PDB:4JQI"
FT TURN 334..338
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 343..351
FT /evidence="ECO:0007829|PDB:4JQI"
FT STRAND 386..392
FT /evidence="ECO:0007829|PDB:6KL7"
SQ SEQUENCE 418 AA; 47020 MW; 0A3C07D71B7ABC55 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
PHREVPESET PVDTNLIELD TNDDDIVFED FARQRLKGMK DDKDEEDDGT GSPHLNNR
