ARRB2_MOUSE
ID ARRB2_MOUSE Reviewed; 410 AA.
AC Q91YI4; Q3TCM2; Q5F2D8; Q5F2E0;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Beta-arrestin-2;
DE AltName: Full=Arrestin beta-2;
GN Name=Arrb2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=11588219; DOI=10.1126/science.1063866;
RA Shenoy S.K., McDonald P.H., Kohout T.A., Lefkowitz R.J.;
RT "Regulation of receptor fate by ubiquitination of activated beta 2-
RT adrenergic receptor and beta-arrestin.";
RL Science 294:1307-1313(2001).
RN [5]
RP SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, AND MUTAGENESIS OF
RP LEU-395.
RX PubMed=12167659; DOI=10.1074/jbc.m207552200;
RA Scott M.G., Le Rouzic E., Perianin A., Pierotti V., Enslen H., Benichou S.,
RA Marullo S., Benmerah A.;
RT "Differential nucleocytoplasmic shuttling of beta-arrestins.
RT Characterization of a leucine-rich nuclear export signal in beta-
RT arrestin2.";
RL J. Biol. Chem. 277:37693-37701(2002).
RN [6]
RP FUNCTION IN ENDOCYTOSIS OF LDLR, AND DISRUPTION PHENOTYPE.
RX PubMed=12944399; DOI=10.1074/jbc.m309450200;
RA Wu J.-H., Peppel K., Nelson C.D., Lin F.-T., Kohout T.A., Miller W.E.,
RA Exum S.T., Freedman N.J.;
RT "The adaptor protein beta-arrestin2 enhances endocytosis of the low density
RT lipoprotein receptor.";
RL J. Biol. Chem. 278:44238-44245(2003).
RN [7]
RP FUNCTION IN AKT1 SIGNALING, ASSOCIATION WITH PP2A, INTERACTION WITH AKT1;
RP GSK3A AND GSK3B, AND DISRUPTION PHENOTYPE.
RX PubMed=16051150; DOI=10.1016/j.cell.2005.05.012;
RA Beaulieu J.-M., Sotnikova T.D., Marion S., Lefkowitz R.J.,
RA Gainetdinov R.R., Caron M.G.;
RT "An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic
RT neurotransmission and behavior.";
RL Cell 122:261-273(2005).
RN [8]
RP FUNCTION IN INTERNALIZATION OF ENG, AND FUNCTION IN TGF-BETA-MEDIATED ERK
RP SIGNALING.
RX PubMed=17540773; DOI=10.1074/jbc.m700176200;
RA Lee N.Y., Blobe G.C.;
RT "The interaction of endoglin with beta-arrestin2 regulates transforming
RT growth factor-beta-mediated ERK activation and migration in endothelial
RT cells.";
RL J. Biol. Chem. 282:21507-21517(2007).
RN [9]
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 [10]
RP INTERACTION WITH CHUK.
RX PubMed=18194271; DOI=10.1111/j.1365-2567.2007.02781.x;
RA Kizaki T., Izawa T., Sakurai T., Haga S., Taniguchi N., Tajiri H.,
RA Watanabe K., Day N.K., Toba K., Ohno H.;
RT "Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear
RT factor-kappaB activation through beta-arrestin 2.";
RL Immunology 124:348-356(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-48, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [12]
RP FUNCTION IN REGULATION OF INNATE IMMUNE RESPONSE, AND DISRUPTION PHENOTYPE.
RX PubMed=18604210; DOI=10.1038/ni.1635;
RA Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H., Sun L.,
RA Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., Pei G., Ge B.-X.;
RT "An essential function for beta-arrestin 2 in the inhibitory signaling of
RT natural killer cells.";
RL Nat. Immunol. 9:898-907(2008).
RN [13]
RP FUNCTION IN INSULIN SIGNALING, INTERACTION WITH SRC; AKT1 AND INSR, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=19122674; DOI=10.1038/nature07617;
RA Luan B., Zhao J., Wu H., Duan B., Shu G., Wang X., Li D., Jia W., Kang J.,
RA Pei G.;
RT "Deficiency of a beta-arrestin-2 signal complex contributes to insulin
RT resistance.";
RL Nature 457:1146-1149(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [15]
RP INTERACTION WITH FFAR4.
RX PubMed=26873857; DOI=10.1124/mol.115.101949;
RA Prihandoko R., Alvarez-Curto E., Hudson B.D., Butcher A.J., Ulven T.,
RA Miller A.M., Tobin A.B., Milligan G.;
RT "Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free
RT Fatty Acid Receptor 4/G Protein-Coupled Receptor 120.";
RL Mol. Pharmacol. 89:505-520(2016).
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. Mediates endocytosis of CCR7 following ligation of CCL19 but
CC not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and
CC P2RY11 and ATP-stimulated internalization of P2RY2. Involved in
CC phosphorylation-dependent internalization of OPRD1 and subsequent
CC recycling or degradation. Involved in ubiquitination of IGF1R. Beta-
CC arrestins function as multivalent adapter proteins that can switch the
CC GPCR from a G-protein signaling mode that transmits short-lived signals
CC from the plasma membrane via small molecule second messengers and ion
CC channels to a beta-arrestin signaling mode that transmits a distinct
CC set of signals that are initiated as the receptor internalizes and
CC transits the intracellular compartment. Acts as signaling scaffold for
CC MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and
CC JNK3 activated by the beta-arrestin scaffold are largely excluded from
CC the nucleus and confined to cytoplasmic locations such as endocytic
CC vesicles, also called beta-arrestin signalosomes. Acts as signaling
CC scaffold for the AKT1 pathway. 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 beta-
CC arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is
CC inhibited by the other respective beta-arrestin form (reciprocal
CC regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated
CC activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2
CC signaling involving ligand CCL19. Is involved in type-1A angiotensin II
CC receptor/AGTR1-mediated ERK activity. Is involved in type-1A
CC angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in
CC dopamine-stimulated AKT1 activity in the striatum by disrupting the
CC association of AKT1 with its negative regulator PP2A. Involved in
CC AGTR1-mediated chemotaxis. Appears to function as signaling scaffold
CC involved in regulation of MIP-1-beta-stimulated CCR5-dependent
CC chemotaxis. Involved in attenuation of NF-kappa-B-dependent
CC transcription in response to GPCR or cytokine stimulation by
CC interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-
CC B-dependent activation by interacting with CHUK. The function is
CC promoted by stimulation of ADRB2 and dephosphorylation of ARRB2.
CC Involved in IL8-mediated granule release in neutrophils (By
CC similarity). Involved in p53/TP53-mediated apoptosis by regulating MDM2
CC and reducing the MDM2-mediated degradation of p53/TP53. May serve as
CC nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved
CC in regulation of gene expression during the early processes of
CC fertilization. Also involved in regulation of receptors other than
CC GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates
CC TGF-beta signaling such as NF-kappa-B activation. Involved in
CC endocytosis of low-density lipoprotein receptor/LDLR. Involved in
CC endocytosis of smoothened homolog/Smo, which also requires GRK2.
CC Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and
CC subsequent TGF-beta-mediated ERK activation and migration of epithelial
CC cells. 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. Involved in insulin resistance by acting as insulin-
CC induced signaling scaffold for SRC, AKT1 and INSR. Involved in
CC regulation of inhibitory signaling of natural killer cells by
CC recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in the internalization
CC of the atypical chemokine receptor ACKR3 (By similarity). Acts as an
CC adapter protein coupling FFAR4 receptor to specific downstream
CC signaling pathways, as well as mediating receptor endocytosis. During
CC the activation step of NLRP3 inflammasome, directly associates with
CC NLRP3 leading to inhibition of pro-inflammatory cytokine release and
CC inhibition of inflammation. {ECO:0000250, ECO:0000250|UniProtKB:P32121,
CC ECO:0000269|PubMed:12944399, ECO:0000269|PubMed:16051150,
CC ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:18337459,
CC ECO:0000269|PubMed:18604210, ECO:0000269|PubMed:19122674}.
CC -!- SUBUNIT: Homooligomer; the self-association is mediated by InsP6-
CC binding (Probable). Heterooligomer with ARRB1; the association is
CC mediated by InsP6-binding. Interacts with ADRB2 AND CHRM2. Interacts
CC with PDE4A. Interacts with PDE4D. Interacts with MAPK10, MAPK1 and
CC MAPK3. Interacts with DRD2. Interacts with FSHR. Interacts with CLTC.
CC Interacts with HTR2C. Interacts with CCR5. Interacts with CXCR4.
CC Interacts with SRC. Interacts with DUSP16; the interaction is
CC interrupted by stimulation of AGTR1 and activation of MAPK10. Interacts
CC with CHUK; the interaction is enhanced stimulation of ADRB2. Interacts
CC with RELA. Interacts with MDM2; the interaction is enhanced by
CC activation of GPCRs. Interacts with SLC9A5. Interacts with TRAF6.
CC Interacts with IGF1R. Interacts with ENG. Interacts with ARRB2.
CC Interacts with KIR2DL1, KIR2DL3 and KIR2DL4. Interacts with LDLR.
CC Interacts with AP2B1. Interacts with C5AR1. Interacts with RAF1.
CC Interacts with MAP2K1. Interacts with MAPK1. Interacts with MAPK10; the
CC interaction enhances MAPK10 activation by MAP3K5. Interacts with
CC MAP2K4; the interaction is enhanced by presence of MAP3K5 and MAPK10.
CC Interacts with MAP3K5. Interacts with AKT1. Interacts with IKBKB and
CC MAP3K14. Interacts with SMO (activated). Interacts with GSK3A and
CC GSK3B. Interacts with CXCR4; the interaction is dependent on C-terminal
CC phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3.
CC Interacts with GPR143. Interacts with HCK and CXCR1 (phosphorylated)
CC (By similarity). Associates with protein phosphatase 2A (PP2A).
CC Interacts with ACKR3 and ACKR4 (By similarity). Interacts with ARRDC1;
CC the interaction is direct (By similarity). Interacts with GPR61, GPR62
CC and GPR135 (By similarity). Interacts (via NACHT and LRR domains) with
CC NLRP3; this interaction is direct and inducible by omega-3
CC polyunsaturated fatty acids (PUFAs) (By similarity). Interacts with
CC FFAR4 (via C-terminus); this interaction is stimulated by long-chain
CC fatty acids (LCFAs) (PubMed:26873857). {ECO:0000250,
CC ECO:0000250|UniProtKB:P32121, ECO:0000269|PubMed:26873857,
CC ECO:0000305}.
CC -!- INTERACTION:
CC Q91YI4; P58660: Card10; NbExp=7; IntAct=EBI-994161, EBI-8344379;
CC Q91YI4; Q7TMA4: Ffar4; NbExp=4; IntAct=EBI-994161, EBI-2912413;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12167659}. Nucleus
CC {ECO:0000269|PubMed:12167659}. Cell membrane
CC {ECO:0000269|PubMed:12167659}. Membrane, clathrin-coated pit
CC {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Note=Translocates to
CC the plasma membrane and colocalizes with antagonist-stimulated GPCRs.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q91YI4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91YI4-2; Sequence=VSP_020652;
CC -!- TISSUE SPECIFICITY: Predominantly localized in neuronal tissues and in
CC the spleen.
CC -!- PTM: Phosphorylated at Thr-383 in the cytoplasm; probably
CC dephosphorylated at the plasma membrane. The phosphorylation does not
CC regulate internalization and recycling of ADRB2, interaction with
CC clathrin or AP2B1 (By similarity). {ECO:0000250}.
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. Stimulation of a class B GPCR promotes a
CC sustained ubiquitination (By similarity). {ECO:0000250}.
CC -!- PTM: Hydroxylation by PHD2 modulates the rate of internalization by
CC slowing down recruitment to the plasma membrane and inhibiting
CC subsequent co-internalization with class A receptors. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Loss of beta-2 adrenergic receptor/ADRB2
CC ubiquitination. Reduction of dopamine-dependent behaviors, loss of Akt1
CC regulation by dopamine in the striatum and disruption of the dopamine-
CC dependent interaction of Akt1 with its negative regulator, protein
CC phosphatase 2A. Increased serum LDL-cholesterol levels upon high fat
CC diet. Exacerbates insulin resistance. Elevated cytotoxicity of natural
CC killer cells and lowered susceptibility to mouse cytomegalovirus
CC infection. {ECO:0000269|PubMed:11588219, ECO:0000269|PubMed:12944399,
CC ECO:0000269|PubMed:16051150, ECO:0000269|PubMed:18604210,
CC ECO:0000269|PubMed:19122674}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR EMBL; AK154874; BAE32894.1; -; mRNA.
DR EMBL; AK159317; BAE34984.1; -; mRNA.
DR EMBL; AK170647; BAE41934.1; -; mRNA.
DR EMBL; AK170889; BAE42096.1; -; mRNA.
DR EMBL; AL596096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016642; AAH16642.1; -; mRNA.
DR CCDS; CCDS24946.1; -. [Q91YI4-1]
DR CCDS; CCDS70226.1; -. [Q91YI4-2]
DR RefSeq; NP_001258287.1; NM_001271358.1. [Q91YI4-2]
DR RefSeq; NP_001258288.1; NM_001271359.1. [Q91YI4-2]
DR RefSeq; NP_001258289.1; NM_001271360.1. [Q91YI4-1]
DR RefSeq; NP_663404.1; NM_145429.5. [Q91YI4-1]
DR AlphaFoldDB; Q91YI4; -.
DR SMR; Q91YI4; -.
DR BioGRID; 229812; 47.
DR CORUM; Q91YI4; -.
DR DIP; DIP-36064N; -.
DR ELM; Q91YI4; -.
DR IntAct; Q91YI4; 34.
DR STRING; 10090.ENSMUSP00000104208; -.
DR iPTMnet; Q91YI4; -.
DR PhosphoSitePlus; Q91YI4; -.
DR SwissPalm; Q91YI4; -.
DR EPD; Q91YI4; -.
DR jPOST; Q91YI4; -.
DR MaxQB; Q91YI4; -.
DR PaxDb; Q91YI4; -.
DR PeptideAtlas; Q91YI4; -.
DR PRIDE; Q91YI4; -.
DR ProteomicsDB; 283247; -. [Q91YI4-1]
DR ProteomicsDB; 283248; -. [Q91YI4-2]
DR Antibodypedia; 23372; 375 antibodies from 37 providers.
DR DNASU; 216869; -.
DR Ensembl; ENSMUST00000079056; ENSMUSP00000078065; ENSMUSG00000060216. [Q91YI4-2]
DR Ensembl; ENSMUST00000102563; ENSMUSP00000099623; ENSMUSG00000060216. [Q91YI4-1]
DR Ensembl; ENSMUST00000102564; ENSMUSP00000099624; ENSMUSG00000060216. [Q91YI4-1]
DR Ensembl; ENSMUST00000108568; ENSMUSP00000104208; ENSMUSG00000060216. [Q91YI4-2]
DR GeneID; 216869; -.
DR KEGG; mmu:216869; -.
DR UCSC; uc007jur.2; mouse. [Q91YI4-1]
DR CTD; 409; -.
DR MGI; MGI:99474; Arrb2.
DR VEuPathDB; HostDB:ENSMUSG00000060216; -.
DR eggNOG; KOG3865; Eukaryota.
DR GeneTree; ENSGT00950000182887; -.
DR HOGENOM; CLU_033484_1_1_1; -.
DR InParanoid; Q91YI4; -.
DR OMA; PHDHIIT; -.
DR PhylomeDB; Q91YI4; -.
DR TreeFam; TF314260; -.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR Reactome; R-MMU-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-MMU-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-MMU-5635838; Activation of SMO.
DR Reactome; R-MMU-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 216869; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Arrb2; mouse.
DR PRO; PR:Q91YI4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q91YI4; protein.
DR Bgee; ENSMUSG00000060216; Expressed in granulocyte and 244 other tissues.
DR ExpressionAtlas; Q91YI4; baseline and differential.
DR Genevisible; Q91YI4; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
DR GO; GO:0031691; F:alpha-1A adrenergic receptor binding; ISO:MGI.
DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; ISO:MGI.
DR GO; GO:0031701; F:angiotensin receptor binding; ISO:MGI.
DR GO; GO:1990763; F:arrestin family protein binding; ISO:MGI.
DR GO; GO:0031748; F:D1 dopamine receptor binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0031762; F:follicle-stimulating hormone receptor binding; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR GO; GO:0031859; F:platelet activating factor receptor binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0031702; F:type 1 angiotensin receptor binding; ISO:MGI.
DR GO; GO:0031826; F:type 2A serotonin receptor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007628; P:adult walking behavior; IMP:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0060326; P:cell chemotaxis; ISO:MGI.
DR GO; GO:0002032; P:desensitization of G protein-coupled receptor signaling pathway by arrestin; ISO:MGI.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0006897; P:endocytosis; ISO:MGI.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; ISO:MGI.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0034260; P:negative regulation of GTPase activity; ISO:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IMP:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:MGI.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IDA:BHF-UCL.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IC:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS:UniProtKB.
DR GO; GO:0032226; P:positive regulation of synaptic transmission, dopaminergic; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:0031623; P:receptor internalization; ISO:MGI.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
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 Alternative splicing; Cell membrane; Coated pit; Cytoplasm;
KW Cytoplasmic vesicle; Hydroxylation; Membrane; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Signal transduction inhibitor;
KW Transport; Ubl conjugation.
FT CHAIN 1..410
FT /note="Beta-arrestin-2"
FT /id="PRO_0000205200"
FT REGION 241..410
FT /note="Interaction with TRAF6"
FT /evidence="ECO:0000250"
FT REGION 364..410
FT /note="Interaction with AP2B1"
FT /evidence="ECO:0000250"
FT MOTIF 386..396
FT /note="[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif"
FT /evidence="ECO:0000250"
FT MOD_RES 48
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 176
FT /note="Hydroxyproline; by PHD2"
FT /evidence="ECO:0000250"
FT MOD_RES 181
FT /note="Hydroxyproline; by PHD2"
FT /evidence="ECO:0000250"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29067"
FT MOD_RES 383
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P29067"
FT VAR_SEQ 360
FT /note="Q -> QSAPIHPPLLCP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020652"
FT MUTAGEN 395
FT /note="L->A: Nuclear localization. Causes nuclear
FT relocalization of MAPK10."
FT /evidence="ECO:0000269|PubMed:12167659"
FT CONFLICT 11
FT /note="K -> R (in Ref. 1; BAE41934)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="T -> N (in Ref. 1; BAE41934)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="S -> Y (in Ref. 1; BAE41934)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 410 AA; 46314 MW; 0DFA73A1C532AE03 CRC64;
MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTC
AFRYGREDLD VLGLSFRKDL FIATYQAFPP MPNPPRPPTR LQDRLLKKLG QHAHPFFFTI
PQNLPCSVTL QPGPEDTGKA CGVDFEIRAF CAKSIEEKSH KRNSVRLIIR KVQFAPETPG
PQPSAETTRH FLMSDRRSLH LEASLDKELY YHGEPLNVNV HVTNNSAKTV KKIRVSVRQY
ADICLFSTAQ YKCPVAQLEQ DDQVSPSSTF CKVYTITPLL SDNREKRGLA LDGQLKHEDT
NLASSTIVKE GANKEVLGIL VSYRVKVKLV VSRGGDVSVE LPFVLMHPKP HDHITLPRPQ
SAPRETDVPV DTNLIEFDTN YATDDDIVFE DFARLRLKGM KDDDCDDQFC
