ID ARRB2_HUMAN Reviewed; 409 AA. AC P32121; B4DLW0; B5B0C0; B7WPL3; D3DTK2; H0Y688; Q0Z8D3; Q2PP19; AC Q6ICT3; Q8N7Y2; Q9UEQ6; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 05-MAR-2002, sequence version 2. DT 01-APR-2015, entry version 150. DE RecName: Full=Beta-arrestin-2; DE AltName: Full=Arrestin beta-2; GN Name=ARRB2; Synonyms=ARB2, ARR2; 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] (ISOFORM 1). RC TISSUE=Thyroid; RX PubMed=1587386; DOI=10.1016/0303-7207(92)90038-8; RA Rapoport B., Kaufman K.D., Chamenbalk G.D.; RT "Cloning of a member of the arrestin family from a human thyroid cDNA RT library."; RL Mol. Cell. Endocrinol. 84:R39-R43(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Yu Q.M., Zhou T.H., Wu Y.L., Cheng Z.J., Ma L., Pei G.; RT "G-protein coupled receptor interaction with beta-arrestin 2 through RT specific agonist stimulation."; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Sanchez-Laorden B.L., Jimenez-Cervantes C., Garcia-Borron J.C.; RT "A new splice-variant of beta-arrestin 2 is involved in agonist- RT induced MC1R endocytosis."; RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lung; RA Kaighin V.A., Martin A.L., Aronstam R.S.; RT "Isolation of cDNA coding for human arrestin, beta 2 (ARRB2), RT transcript variant 1."; RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Brain, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [9] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle, and Pancreas; 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 [11] RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH GPCRS. RX PubMed=9346876; DOI=10.1074/jbc.272.44.27497; RA Barak L.S., Ferguson S.S.G., Zhang J., Caron M.G.; RT "A beta-arrestin/green fluorescent protein biosensor for detecting G RT protein-coupled receptor activation."; RL J. Biol. Chem. 272:27497-27500(1997). RN [12] RP FUNCTION IN IN INTERNALIZATION OF CXCR4, INTERACTION WITH CXCR4, AND RP MUTAGENESIS OF VAL-54. RX PubMed=10644702; DOI=10.1074/jbc.275.4.2479; RA Cheng Z.J., Zhao J., Sun Y., Hu W., Wu Y.L., Cen B., Wu G.-X., Pei G.; RT "beta-arrestin differentially regulates the chemokine receptor CXCR4- RT mediated signaling and receptor internalization, and this implicates RT multiple interaction sites between beta-arrestin and CXCR4."; RL J. Biol. Chem. 275:2479-2485(2000). RN [13] 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 [14] 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 [15] RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH ANTAGONIST-STIMULATED RP GPCRS. RX PubMed=11279203; DOI=10.1074/jbc.M101450200; RA Oakley R.H., Laporte S.A., Holt J.A., Barak L.S., Caron M.G.; RT "Molecular determinants underlying the formation of stable RT intracellular G protein-coupled receptor-beta-arrestin complexes after RT receptor endocytosis*."; RL J. Biol. Chem. 276:19452-19460(2001). RN [16] RP FUNCTION IN INTERNALIZATION OF ADBR2, PHOSPHORYLATION AT THR-382, RP INTERACTION WITH AP2B1; CLATHRIN AND SRC, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF THR-382. RX PubMed=11877451; DOI=10.1074/jbc.M201379200; RA Kim Y.-M., Barak L.S., Caron M.G., Benovic J.L.; RT "Regulation of arrestin-3 phosphorylation by casein kinase II."; RL J. Biol. Chem. 277:16837-16846(2002). RN [17] RP FUNCTION IN TP53-MEDIATED APOPTOSIS, AND INTERACTION WITH MDM2. RX PubMed=12488444; DOI=10.1074/jbc.M210350200; RA Wang P., Gao H., Ni Y., Wang B., Wu Y., Ji L., Qin L., Ma L., Pei G.; RT "Beta-arrestin 2 functions as a G-protein-coupled receptor-activated RT regulator of oncoprotein Mdm2."; RL J. Biol. Chem. 278:6363-6370(2003). RN [18] RP FUNCTION IN DESENSITIZATION OF ADRB2, FUNCTION IN INTERNALIZATION OF RP ADRB2, FUNCTION IN INTERNALIZATION OF AGTR1, AND FUNCTION IN RP AGTR1-MEDIATED ERK SIGNALING. RX PubMed=12582207; DOI=10.1073/pnas.262789099; RA Ahn S., Nelson C.D., Garrison T.R., Miller W.E., Lefkowitz R.J.; RT "Desensitization, internalization, and signaling functions of beta- RT arrestins demonstrated by RNA interference."; RL Proc. Natl. Acad. Sci. U.S.A. 100:1740-1744(2003). RN [19] RP FUNCTION IN AGTR1-MEDIATED ERK SIGNALING. RX PubMed=12949261; DOI=10.1073/pnas.1834556100; RA Wei H., Ahn S., Shenoy S.K., Karnik S.S., Hunyady L., Luttrell L.M., RA Lefkowitz R.J.; RT "Independent beta-arrestin 2 and G protein-mediated pathways for RT angiotensin II activation of extracellular signal-regulated kinases 1 RT and 2."; RL Proc. Natl. Acad. Sci. U.S.A. 100:10782-10787(2003). RN [20] RP FUNCTION IN ENDOCYTOSIS OF TGFBR2 AND TGFBR3, FUNCTION IN TGF-BETA RP SIGNALING, AND SUBCELLULAR LOCATION. RX PubMed=12958365; DOI=10.1126/science.1083195; RA Chen W., Kirkbride K.C., How T., Nelson C.D., Mo J., Frederick J.P., RA Wang X.-F., Lefkowitz R.J., Blobe G.C.; RT "Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor RT and down-regulation of its signaling."; RL Science 301:1394-1397(2003). RN [21] 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 [22] RP FUNCTION IN CCR7-MEDIATED ERK SIGNALING. RX PubMed=15054093; DOI=10.1074/jbc.M402125200; RA Kohout T.A., Nicholas S.L., Perry S.J., Reinhart G., Junger S., RA Struthers R.S.; RT "Differential desensitization, receptor phosphorylation, beta-arrestin RT recruitment, and ERK1/2 activation by the two endogenous ligands for RT the CC chemokine receptor 7."; RL J. Biol. Chem. 279:23214-23222(2004). RN [23] RP FUNCTION IN AGTR1-MEDIATED ERK SIGNALING. RX PubMed=15205453; DOI=10.1074/jbc.M405878200; RA Ahn S., Shenoy S.K., Wei H., Lefkowitz R.J.; RT "Differential kinetic and spatial patterns of beta-arrestin and G RT protein-mediated ERK activation by the angiotensin II receptor."; RL J. Biol. Chem. 279:35518-35525(2004). RN [24] RP FUNCTION IN REGULATION OF NF-KAPPA-B, SUBCELLULAR LOCATION, AND RP INTERACTION WITH CHUK AND RELA. RX PubMed=15125834; DOI=10.1016/S1097-2765(04)00216-3; RA Gao H., Sun Y., Wu Y., Luan B., Wang Y., Qu B., Pei G.; RT "Identification of beta-arrestin2 as a G protein-coupled receptor- RT stimulated regulator of NF-kappaB pathways."; RL Mol. Cell 14:303-317(2004). RN [25] RP FUNCTION IN INTERNALIZATION OF SMO. RX PubMed=15618519; DOI=10.1126/science.1104135; RA Chen W., Ren X.R., Nelson C.D., Barak L.S., Chen J.K., Beachy P.A., RA de Sauvage F., Lefkowitz R.J.; RT "Activity-dependent internalization of smoothened mediated by beta- RT arrestin 2 and GRK2."; RL Science 306:2257-2260(2004). RN [26] 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 [27] RP INTERACTION WITH DUSP16, AND SUBCELLULAR LOCATION. RX PubMed=15888437; DOI=10.1074/jbc.M501926200; RA Willoughby E.A., Collins M.K.; RT "Dynamic interaction between the dual specificity phosphatase MKP7 and RT the JNK3 scaffold protein beta-arrestin 2."; RL J. Biol. Chem. 280:25651-25658(2005). RN [28] 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 [29] RP FUNCTION IN F2LR1-MEDIATED ERK SIGNALING. 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 [30] RP FUNCTION IN AGTR1-MEDIATED CHEMOTAXIS. RX PubMed=15635042; DOI=10.1124/mol.104.006270; RA Hunton D.L., Barnes W.G., Kim J., Ren X.-R., Violin J.D., Reiter E., RA Milligan G., Patel D.D., Lefkowitz R.J.; RT "Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated RT pathway of chemotaxis."; RL Mol. Pharmacol. 67:1229-1236(2005). RN [31] 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 [32] RP FUNCTION IN ENDOCYTOSIS OF SLC9A5, AND INTERACTION WITH SLC9A5. RX PubMed=15699339; DOI=10.1073/pnas.0407444102; RA Szabo E.Z., Numata M., Lukashova V., Iannuzzi P., Orlowski J.; RT "beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ RT exchanger NHE5 isoform."; RL Proc. Natl. Acad. Sci. U.S.A. 102:2790-2795(2005). RN [33] RP INTERACTION WITH AP2B1. 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 [34] RP FUNCTION IN ADRB2-MEDIATED ERK SIGNALING. 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 [35] RP INTERACTION WITH HTR2C. RX PubMed=16319069; DOI=10.1074/jbc.M508074200; RA Marion S., Oakley R.H., Kim K.-M., Caron M.G., Barak L.S.; RT "A beta-arrestin binding determinant common to the second RT intracellular loops of rhodopsin family G protein-coupled receptors."; RL J. Biol. Chem. 281:2932-2938(2006). RN [36] 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 [37] RP FUNCTION IN THE NUCLEUS OF SPERMATOZOA, SUBCELLULAR LOCATION, AND RP INTERACTION WITH DHX8; GAPDHS; H2AFX; KIF14 AND RCC1. RX PubMed=16820410; DOI=10.1242/jcs.03046; RA Neuhaus E.M., Mashukova A., Barbour J., Wolters D., Hatt H.; RT "Novel function of beta-arrestin2 in the nucleus of mature RT spermatozoa."; RL J. Cell Sci. 119:3047-3056(2006). RN [38] 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 [39] 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 [40] RP FUNCTION IN INTERNALIZATION OF ENG, FUNCTION IN TGF-BETA-MEDIATED ERK RP SIGNALING, SUBCELLULAR LOCATION, AND INTERACTION WITH ENG. RX PubMed=17540773; DOI=10.1074/jbc.M700176200; RA Lee N.Y., Blobe G.C.; RT "The interaction of endoglin with beta-arrestin2 regulates RT transforming growth factor-beta-mediated ERK activation and migration RT in endothelial cells."; RL J. Biol. Chem. 282:21507-21517(2007). RN [41] RP FUNCTION IN INTERNALIZATION OF OPRD1, AND FUNCTION IN DEGRADATION OF RP 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 [42] RP FUNCTION IN REGULATION OF INNATE IMMUNE RESPONSE, AND INTERACTION WITH RP KIR2DL1; KIR2DL3 AND KIR2DL4. 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., RA Sun L., Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., RA Pei G., Ge B.-X.; RT "An essential function for beta-arrestin 2 in the inhibitory signaling RT of natural killer cells."; RL Nat. Immunol. 9:898-907(2008). RN [43] RP FUNCTION IN TGFBR3-MEDIATED NF-KAPPA-B REGULATION. RX PubMed=19325136; DOI=10.1093/carcin/bgp071; RA You H.J., How T., Blobe G.C.; RT "The type III transforming growth factor-beta receptor negatively RT regulates nuclear factor kappa B signaling through its interaction RT with beta-arrestin2."; RL Carcinogenesis 30:1281-1287(2009). RN [44] 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 [45] 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 [46] 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 [47] 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 [48] RP INTERACTION WITH CXCR4, AND FUNCTION. RX PubMed=20048153; DOI=10.1074/jbc.M109.091173; RA Busillo J.M., Armando S., Sengupta R., Meucci O., Bouvier M., RA Benovic J.L.; RT "Site-specific phosphorylation of CXCR4 is dynamically regulated by RT multiple kinases and results in differential modulation of CXCR4 RT signaling."; RL J. Biol. Chem. 285:7805-7817(2010). RN [49] RP HYDROXYLATION AT PRO-176 AND PRO-181. RX PubMed=21255264; DOI=10.1111/j.1582-4934.2011.01268.x; RA Yan B., Huo Z., Liu Y., Lin X., Li J., Peng L., Zhao H., Zhou Z.N., RA Liang X., Liu Y., Zhu W., Liang D., Li L., Sun Y., Cui J., Chen Y.H.; RT "Prolyl hydroxylase 2: a novel regulator of beta2 -adrenoceptor RT internalization."; RL J. Cell. Mol. Med. 15:2712-2722(2011). RN [50] RP INTERACTION WITH ACKR3. RX PubMed=22300987; DOI=10.1016/j.biocel.2012.01.007; RA Ray P., Mihalko L.A., Coggins N.L., Moudgil P., Ehrlich A., RA Luker K.E., Luker G.D.; RT "Carboxy-terminus of CXCR7 regulates receptor localization and RT function."; RL Int. J. Biochem. Cell Biol. 44:669-678(2012). RN [51] 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 [52] RP SUBCELLULAR LOCATION, 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). 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. Mediates CC endocytosis of CCR7 following ligation of CCL19 but not CCL21. CC Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and CC ATP-stimulated internalization of P2RY2. Involved in CC phosphorylation-dependent internalization of OPRD1 and subsequent CC recycling or degradation. Involved in ubiquitination of IGF1R. CC Beta-arrestins function as multivalent adapter proteins that can CC switch the GPCR from a G-protein signaling mode that transmits CC short-lived signals from the plasma membrane via small molecule CC second messengers and ion channels to a beta-arrestin signaling CC mode that transmits a distinct set of signals that are initiated CC as the receptor internalizes and transits the intracellular CC compartment. Acts as signaling scaffold for MAPK pathways such as CC MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by CC the beta-arrestin scaffold are largely excluded from the nucleus CC and confined to cytoplasmic locations such as endocytic vesicles, CC also called beta-arrestin signalosomes. Acts as signaling scaffold CC for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated CC signaling relies on both ARRB1 and ARRB2 (codependent regulation) CC include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin- CC 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- CC mediated activation (reciprocal regulation). Involved in CCR7- CC mediated ERK1/2 signaling involving ligand CCL19. Is involved in CC type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is CC involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 CC activity. Is involved in dopamine-stimulated AKT1 activity in the CC striatum by disrupting the association of AKT1 with its negative CC regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to CC function as signaling scaffold involved in regulation of MIP-1- CC beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation CC of NF-kappa-B-dependent transcription in response to GPCR or CC cytokine stimulation by interacting with and stabilizing CHUK. CC Suppresses UV-induced NF-kappa-B-dependent activation by CC interacting with CHUK. The function is promoted by stimulation of CC ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53- CC mediated apoptosis by regulating MDM2 and reducing the MDM2- CC mediated degradation of p53/TP53. May serve as nuclear messenger CC for GPCRs. Upon stimulation of OR1D2, may be involved in CC 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- CC regulates TGF-beta signaling such as NF-kappa-B activation. CC Involved in endocytosis of low-density lipoprotein receptor/LDLR. CC Involved in endocytosis of smoothened homolog/Smo, which also CC requires ADRBK1. Involved in endocytosis of SLC9A5. Involved in CC endocytosis of ENG and subsequent TGF-beta-mediated ERK activation CC and migration of epithelial cells. Involved in Toll-like receptor CC and IL-1 receptor signaling through the interaction with TRAF6 CC which prevents TRAF6 autoubiquitination and oligomerization CC required for activation of NF-kappa-B and JUN. Involved in insulin CC resistance by acting as insulin-induced signaling scaffold for CC SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling CC of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. CC Involved in IL8-mediated granule release in neutrophils. Involved CC in the internalization of the atypical chemokine receptor ACKR3. CC {ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:11877451, CC ECO:0000269|PubMed:12488444, ECO:0000269|PubMed:12582207, CC ECO:0000269|PubMed:12949261, ECO:0000269|PubMed:12958365, CC ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15054093, CC ECO:0000269|PubMed:15125834, ECO:0000269|PubMed:15205453, CC ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15618519, CC ECO:0000269|PubMed:15635042, ECO:0000269|PubMed:15671180, CC ECO:0000269|PubMed:15699339, 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:16820410, ECO:0000269|PubMed:17540773, CC ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:18604210, CC ECO:0000269|PubMed:19325136, ECO:0000269|PubMed:19620252, CC ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:20048153, CC ECO:0000269|PubMed:22457824}. 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. CC Interacts with PDE4A. Interacts with PDE4D. Interacts with MAPK10, CC MAPK1 and MAPK3. Interacts with DRD2. Interacts with FSHR. CC Interacts with CLTC. Interacts with HTR2C. Interacts with CCR5. CC Interacts with CXCR4. Interacts with SRC. Interacts with DUSP16; CC the interaction is interrupted by stimulation of AGTR1 and CC activation of MAPK10. Interacts with CHUK; the interaction is CC enhanced stimulation of ADRB2. Interacts with RELA. Interacts with CC MDM2; the interaction is enhanced by activation of GPCRs. CC Interacts with SLC9A5. Interacts with TRAF6. Interacts with IGF1R. CC Interacts with ENG. Interacts with KIR2DL1, KIR2DL3 and KIR2DL4. CC Interacts with LDLR. Interacts with AP2B1. Interacts with C5AR1. CC Interacts with RAF1. Interacts with MAP2K1. Interacts with MAPK1. CC Interacts with MAPK10; the interaction enhances MAPK10 activation CC by MAP3K5. Interacts with MAP2K4; the interaction is enhanced by CC presence of MAP3K5 and MAPK10. Interacts with MAP3K5. Interacts CC with AKT1. Interacts with IKBKB and MAP3K14. Interacts with SMO CC (activated). Interacts with GSK3A and GSK3B. Associates with CC protein phosphatase 2A (PP2A) (By similarity). Interacts with CC DHX8; the interaction is detected in the nucleus upon OR1D2 CC stimulation. Interacts with GAPDHS; the interaction is detected in CC the nucleus upon OR1D2 stimulation. Interacts with H2AFX; the CC interaction is detected in the nucleus upon OR1D2 stimulation. CC Interacts with KIF14; the interaction is detected in the nucleus CC upon OR1D2 stimulation. Interacts with RCC1; the interaction is CC detected in the nucleus upon OR1D2 stimulation. Interacts with CC CXCR4; the interaction is dependent on C-terminal phosphorylation CC of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with CC GPR143. Interacts with HCK and CXCR1 (phosphorylated). Interacts CC with ACKR3 and ACKR4. {ECO:0000250, ECO:0000269|PubMed:10644702, CC ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11877451, CC ECO:0000269|PubMed:12488444, ECO:0000269|PubMed:15125834, CC ECO:0000269|PubMed:15699339, ECO:0000269|PubMed:15878855, CC ECO:0000269|PubMed:15888437, ECO:0000269|PubMed:16144840, CC ECO:0000269|PubMed:16319069, ECO:0000269|PubMed:16378096, CC ECO:0000269|PubMed:16516836, ECO:0000269|PubMed:16524428, CC ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17540773, CC ECO:0000269|PubMed:18604210, ECO:0000269|PubMed:19363159, CC ECO:0000269|PubMed:19782076, ECO:0000269|PubMed:20048153, CC ECO:0000269|PubMed:22300987, ECO:0000269|PubMed:22457824, CC ECO:0000269|PubMed:23341447, ECO:0000305}. CC -!- INTERACTION: CC P31750:Akt1 (xeno); NbExp=3; IntAct=EBI-714559, EBI-298707; CC P62158:CALM3; NbExp=3; IntAct=EBI-714559, EBI-397435; CC O15111:CHUK; NbExp=3; IntAct=EBI-714559, EBI-81249; CC P35221:CTNNA1; NbExp=3; IntAct=EBI-714559, EBI-701918; CC Q14247:CTTN; NbExp=2; IntAct=EBI-714559, EBI-351886; CC P06396:GSN; NbExp=3; IntAct=EBI-714559, EBI-351506; CC P11142:HSPA8; NbExp=4; IntAct=EBI-714559, EBI-351896; CC Q13233:MAP3K1; NbExp=2; IntAct=EBI-714559, EBI-49776; CC Q99683:MAP3K5; NbExp=2; IntAct=EBI-714559, EBI-476263; CC P28482:MAPK1; NbExp=3; IntAct=EBI-714559, EBI-959949; CC P19338:NCL; NbExp=3; IntAct=EBI-714559, EBI-346967; CC Q14978:NOLC1; NbExp=3; IntAct=EBI-714559, EBI-396155; CC Q9Q2G4:ORF (xeno); NbExp=3; IntAct=EBI-714559, EBI-6248094; CC P14618:PKM; NbExp=4; IntAct=EBI-714559, EBI-353408; CC P35813:PPM1A; NbExp=3; IntAct=EBI-714559, EBI-989143; CC O75688:PPM1B; NbExp=4; IntAct=EBI-714559, EBI-1047039; CC Q13523:PRPF4B; NbExp=3; IntAct=EBI-714559, EBI-395940; CC P40417:rl (xeno); NbExp=4; IntAct=EBI-714559, EBI-867790; CC P06702:S100A9; NbExp=2; IntAct=EBI-714559, EBI-1055001; CC Q15208:STK38; NbExp=3; IntAct=EBI-714559, EBI-458376; CC Q15750:TAB1; NbExp=3; IntAct=EBI-714559, EBI-358643; CC Q13428:TCOF1; NbExp=3; IntAct=EBI-714559, EBI-396105; CC P27348:YWHAQ; NbExp=3; IntAct=EBI-714559, EBI-359854; CC O95218:ZRANB2; NbExp=4; IntAct=EBI-714559, EBI-1051583; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane. Membrane, CC clathrin-coated pit {ECO:0000250}. Cytoplasmic vesicle. CC Note=Translocates to the plasma membrane and colocalizes with CC antagonist-stimulated GPCRs. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P32121-1; Sequence=Displayed; CC Name=2; CC IsoId=P32121-3; Sequence=VSP_008195; CC Name=3; CC IsoId=P32121-2; Sequence=VSP_008194, VSP_008195; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=P32121-4; Sequence=VSP_044697; CC Note=No experimental confirmation available.; CC Name=5; CC IsoId=P32121-5; Sequence=VSP_008194; 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. {ECO:0000250}. CC -!- PTM: Phosphorylated at Thr-382 in the cytoplasm; probably CC dephosphorylated at the plasma membrane. The phosphorylation does CC not regulate internalization and recycling of ADRB2, interaction CC with clathrin or AP2B1. {ECO:0000269|PubMed:11877451}. CC -!- PTM: The ubiquitination status appears to regulate the formation CC and trafficking of beta-arrestin-GPCR complexes and signaling. CC Ubiquitination appears to occurr GPCR-specifc. 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. Stimulation of a CC class B GPCR promotes a sustained ubiquitination. CC {ECO:0000269|PubMed:19363159}. CC -!- PTM: Hydroxylation by PHD2 modulates the rate of internalization CC by slowing down recruitment to the plasma membrane and inhibiting CC subsequent co-internalization with class A receptors. CC {ECO:0000269|PubMed:21255264}. CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Arrestin entry; CC URL="http://en.wikipedia.org/wiki/Arrestin"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z11501; CAA77577.1; -; mRNA. DR EMBL; AF106941; AAC99468.1; -; mRNA. DR EMBL; DQ664180; ABG47460.1; -; mRNA. DR EMBL; EU883572; ACG60646.1; -; mRNA. DR EMBL; AK097542; BAC05094.1; -; mRNA. DR EMBL; AK297181; BAG59672.1; -; mRNA. DR EMBL; CR450310; CAG29306.1; -; mRNA. DR EMBL; DQ314866; ABC40725.1; -; Genomic_DNA. DR EMBL; AC091153; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90421.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90422.1; -; Genomic_DNA. DR EMBL; BC007427; AAH07427.1; -; mRNA. DR EMBL; BC067368; AAH67368.1; -; mRNA. DR CCDS; CCDS11050.1; -. [P32121-1] DR CCDS; CCDS11051.1; -. [P32121-5] DR CCDS; CCDS58504.1; -. [P32121-4] DR CCDS; CCDS58505.1; -. [P32121-2] DR PIR; S18984; S18984. DR RefSeq; NP_001244257.1; NM_001257328.1. [P32121-4] DR RefSeq; NP_001244258.1; NM_001257329.1. DR RefSeq; NP_001244259.1; NM_001257330.1. [P32121-3] DR RefSeq; NP_001244260.1; NM_001257331.1. [P32121-2] DR RefSeq; NP_004304.1; NM_004313.3. [P32121-1] DR RefSeq; NP_945355.1; NM_199004.1. [P32121-5] DR UniGene; Hs.435811; -. DR ProteinModelPortal; P32121; -. DR SMR; P32121; 6-393. DR BioGrid; 106902; 327. DR DIP; DIP-40089N; -. DR IntAct; P32121; 288. DR MINT; MINT-216692; -. DR STRING; 9606.ENSP00000269260; -. DR PhosphoSite; P32121; -. DR DMDM; 20141230; -. DR MaxQB; P32121; -. DR PaxDb; P32121; -. DR PRIDE; P32121; -. DR DNASU; 409; -. DR Ensembl; ENST00000269260; ENSP00000269260; ENSG00000141480. [P32121-1] DR Ensembl; ENST00000346341; ENSP00000341895; ENSG00000141480. [P32121-2] DR Ensembl; ENST00000381488; ENSP00000370898; ENSG00000141480. [P32121-5] DR Ensembl; ENST00000412477; ENSP00000403701; ENSG00000141480. [P32121-4] DR GeneID; 409; -. DR KEGG; hsa:409; -. DR UCSC; uc002fyj.3; human. [P32121-1] DR UCSC; uc002fyl.3; human. [P32121-3] DR UCSC; uc002fym.3; human. [P32121-2] DR CTD; 409; -. DR GeneCards; GC17P004613; -. DR HGNC; HGNC:712; ARRB2. DR MIM; 107941; gene. DR neXtProt; NX_P32121; -. DR PharmGKB; PA60; -. DR eggNOG; NOG302111; -. DR GeneTree; ENSGT00390000013152; -. DR HOGENOM; HOG000231319; -. DR HOVERGEN; HBG002399; -. DR InParanoid; P32121; -. DR KO; K04439; -. DR OMA; KPHDHIT; -. DR OrthoDB; EOG79W954; -. DR PhylomeDB; P32121; -. DR TreeFam; TF314260; -. DR Reactome; REACT_118614; Activated NOTCH1 Transmits Signal to the Nucleus. DR Reactome; REACT_21384; Thrombin signalling through proteinase activated receptors (PARs). DR Reactome; REACT_263890; WNT5A-dependent internalization of FZD4. DR Reactome; REACT_267753; Activation of SMO. DR SignaLink; P32121; -. DR ChiTaRS; ARRB2; human. DR GeneWiki; Arrestin_beta_2; -. DR GenomeRNAi; 409; -. DR NextBio; 1719; -. DR PRO; PR:P32121; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P32121; -. DR CleanEx; HS_ARRB2; -. DR ExpressionAtlas; P32121; baseline and differential. DR Genevestigator; P32121; -. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0005905; C: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:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0031701; F:angiotensin receptor binding; IPI:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0001664; F:G-protein coupled receptor binding; IPI:UniProtKB. DR GO; GO:0032947; F:protein complex scaffold; IDA:BHF-UCL. DR GO; GO:0005102; F:receptor binding; IPI:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB. DR GO; GO:0002032; P:desensitization of G-protein coupled receptor protein signaling pathway by arrestin; IMP:UniProtKB. DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl. DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IEA:Ensembl. DR GO; GO:0002031; P:G-protein coupled receptor internalization; IDA:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl. DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IEA:Ensembl. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IMP: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:0090201; P:negative regulation of release of cytochrome c from mitochondria; IEA:Ensembl. DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Ensembl. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IGI:BHF-UCL. DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:UniProtKB. DR GO; GO:0032226; P:positive regulation of synaptic transmission, dopaminergic; IEA:Ensembl. 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:0031623; P:receptor internalization; IDA:BHF-UCL. DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR Gene3D; 2.60.40.640; -; 1. DR Gene3D; 2.60.40.840; -; 1. DR InterPro; IPR000698; Arrestin. DR InterPro; IPR011021; Arrestin-like_N. DR InterPro; IPR014752; Arrestin_C. 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; Complete proteome; KW Cytoplasm; Cytoplasmic vesicle; Hydroxylation; Membrane; Nucleus; KW Phosphoprotein; Protein transport; Reference proteome; KW Signal transduction inhibitor; Transport; Ubl conjugation. FT CHAIN 1 409 Beta-arrestin-2. FT /FTId=PRO_0000205199. FT REGION 240 409 Interaction with TRAF6. FT REGION 363 409 Interaction with AP2B1. FT MOTIF 385 395 [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. FT MOD_RES 48 48 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q91YI4}. FT MOD_RES 176 176 Hydroxyproline; by PHD2. FT {ECO:0000269|PubMed:21255264}. FT MOD_RES 181 181 Hydroxyproline; by PHD2. FT {ECO:0000269|PubMed:21255264}. FT MOD_RES 360 360 Phosphoserine. FT {ECO:0000250|UniProtKB:P29067}. FT MOD_RES 382 382 Phosphothreonine. FT {ECO:0000269|PubMed:11877451}. FT VAR_SEQ 39 53 Missing (in isoform 3 and isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_008194. FT VAR_SEQ 119 119 T -> TVRMPLPSEGQGAGAGTVSGVG (in isoform FT 4). {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_044697. FT VAR_SEQ 360 360 S -> SAPTPTPPLPVPP (in isoform 2 and FT isoform 3). {ECO:0000303|PubMed:14702039, FT ECO:0000303|Ref.3}. FT /FTId=VSP_008195. FT MUTAGEN 11 11 K->A: Abolishes interaction with CHUK; FT when associated with A-12; A-230 and A- FT 231. FT MUTAGEN 12 12 K->A: Abolishes interaction with CHUK; FT when associated with A-11; A-230 and A- FT 231. FT MUTAGEN 54 54 V->A: Inhibits internalization of CXCR4; FT no effect on interaction with CXCR4. FT {ECO:0000269|PubMed:10644702}. FT MUTAGEN 230 230 K->A: Abolishes interaction with CHUK; FT when associated with A-11; A-12 and A- FT 231. FT MUTAGEN 231 231 K->A: Abolishes interaction with CHUK; FT when associated with A-11; A-12 and A- FT 230. FT MUTAGEN 360 360 S->A,D: Reduces interaction with CHUK; FT when associated with A-382. FT MUTAGEN 382 382 T->A,D: Reduces interaction with CHUK; FT when associated with A-360. FT {ECO:0000269|PubMed:11877451}. FT MUTAGEN 382 382 T->A: Loss of phosphorylation. FT {ECO:0000269|PubMed:11877451}. FT CONFLICT 13 13 S -> P (in Ref. 5; BAG59672). FT {ECO:0000305}. FT CONFLICT 189 189 R -> P (in Ref. 1; CAA77577). FT {ECO:0000305}. FT CONFLICT 190 190 H -> R (in Ref. 3; ABG47460). FT {ECO:0000305}. FT CONFLICT 192 192 L -> P (in Ref. 6; CAG29306). FT {ECO:0000305}. FT CONFLICT 366 366 D -> G (in Ref. 5; BAG59672). FT {ECO:0000305}. SQ SEQUENCE 409 AA; 46106 MW; DEEC507D4A7B84FF CRC64; MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTC AFRYGREDLD VLGLSFRKDL FIATYQAFPP VPNPPRPPTR LQDRLLRKLG QHAHPFFFTI PQNLPCSVTL QPGPEDTGKA CGVDFEIRAF CAKSLEEKSH KRNSVRLVIR KVQFAPEKPG PQPSAETTRH FLMSDRSLHL EASLDKELYY HGEPLNVNVH VTNNSTKTVK KIKVSVRQYA DICLFSTAQY KCPVAQLEQD DQVSPSSTFC KVYTITPLLS DNREKRGLAL DGKLKHEDTN LASSTIVKEG ANKEVLGILV SYRVKVKLVV SRGGDVSVEL PFVLMHPKPH DHIPLPRPQS AAPETDVPVD TNLIEFDTNY ATDDDIVFED FARLRLKGMK DDDYDDQLC //