ARRB2_HUMAN
ID ARRB2_HUMAN Reviewed; 409 AA.
AC P32121; B4DLW0; B5B0C0; B7WPL3; D3DTK2; H0Y688; Q0Z8D3; Q2PP19; Q6ICT3;
AC Q8N7Y2; Q9UEQ6;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 05-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Beta-arrestin-2;
DE AltName: Full=Arrestin beta-2;
DE AltName: Full=Non-visual arrestin-3 {ECO:0000303|PubMed:23886940};
GN Name=ARRB2; Synonyms=ARB2, ARR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (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-induced
RT 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), transcript
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., 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 the
RT 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (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 project:
RT 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 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 GPCRS.
RX PubMed=10748214; DOI=10.1074/jbc.m910348199;
RA Oakley R.H., Laporte S.A., Holt J.A., Caron M.G., Barak L.S.;
RT "Differential affinities of visual arrestin, beta arrestin1, and beta
RT arrestin2 for G protein-coupled receptors delineate two major classes of
RT receptors.";
RL J. Biol. Chem. 275:17201-17210(2000).
RN [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., 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 [15]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH ANTAGONIST-STIMULATED 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 intracellular G
RT protein-coupled receptor-beta-arrestin complexes after receptor
RT 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 ADRB2,
RP FUNCTION IN INTERNALIZATION OF AGTR1, AND FUNCTION IN AGTR1-MEDIATED ERK
RP 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 and
RT 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 and
RT 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 the CC
RT 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 protein-
RT 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 INTERACTION
RP 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-arrestin
RT 2 and GRK2.";
RL Science 306:2257-2260(2004).
RN [26]
RP FUNCTION IN UBIQUITINATION OF IGF1R, AND INTERACTION WITH IGF1R AND MDM2.
RX PubMed=15878855; DOI=10.1074/jbc.m501129200;
RA Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A.,
RA Lefkowitz R.J., Larsson O.;
RT "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the
RT insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3
RT ligase.";
RL J. Biol. Chem. 280:24412-24419(2005).
RN [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 the
RT JNK3 scaffold protein beta-arrestin 2.";
RL J. Biol. Chem. 280:25651-25658(2005).
RN [28]
RP FUNCTION IN INTERNALIZATION OF CCR5, AND INTERACTION WITH CCR5.
RX PubMed=16144840; DOI=10.1074/jbc.m500535200;
RA Huettenrauch F., Pollok-Kopp B., Oppermann M.;
RT "G protein-coupled receptor kinases promote phosphorylation and beta-
RT arrestin-mediated internalization of CCR5 homo- and hetero-oligomers.";
RL J. Biol. Chem. 280:37503-37515(2005).
RN [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., Morris D.R.,
RA Trejo J.;
RT "Multiple independent functions of arrestins in the regulation of protease-
RT activated receptor-2 signaling and trafficking.";
RL Mol. Pharmacol. 67:78-87(2005).
RN [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 pathway
RT 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 beta-
RT 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 endocytic
RT 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., Madabushi S.,
RA Reiter E., Premont R.T., Lichtarge O., Lefkowitz R.J.;
RT "beta-arrestin-dependent, G protein-independent ERK1/2 activation by the
RT beta2 adrenergic receptor.";
RL J. Biol. Chem. 281:1261-1273(2006).
RN [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 intracellular
RT 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., Lefkowitz R.J.;
RT "Distinct beta-arrestin- and G protein-dependent pathways for parathyroid
RT hormone receptor-stimulated ERK1/2 activation.";
RL J. Biol. Chem. 281:10856-10864(2006).
RN [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 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., 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 transforming
RT growth factor-beta-mediated ERK activation and migration in endothelial
RT cells.";
RL J. Biol. Chem. 282:21507-21517(2007).
RN [41]
RP FUNCTION IN INTERNALIZATION OF OPRD1, AND FUNCTION IN DEGRADATION OF OPRD1.
RX PubMed=18419762; DOI=10.1111/j.1471-4159.2008.05431.x;
RA Zhang X., Wang F., Chen X., Chen Y., Ma L.;
RT "Post-endocytic fates of delta-opioid receptor are regulated by GRK2-
RT mediated receptor phosphorylation and distinct beta-arrestin isoforms.";
RL J. Neurochem. 106:781-792(2008).
RN [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., 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 [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 regulates
RT nuclear factor kappa B signaling through its interaction with beta-
RT 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 the
RT 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., 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 the E3
RT 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., 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., Luker K.E.,
RA Luker G.D.;
RT "Carboxy-terminus of CXCR7 regulates receptor localization and function.";
RL Int. J. Biochem. Cell Biol. 44:669-678(2012).
RN [51]
RP FUNCTION, AND INTERACTION WITH FFAR4.
RX PubMed=22282525; DOI=10.1124/mol.111.077388;
RA Watson S.J., Brown A.J., Holliday N.D.;
RT "Differential signaling by splice variants of the human free fatty acid
RT receptor GPR120.";
RL Mol. Pharmacol. 81:631-642(2012).
RN [52]
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 [53]
RP FUNCTION, AND INTERACTION WITH NLRP3.
RX PubMed=23809162; DOI=10.1016/j.immuni.2013.05.015;
RA Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C.,
RA Guarda G., Tian Z., Tschopp J., Zhou R.;
RT "Omega-3 fatty acids prevent inflammation and metabolic disorder through
RT inhibition of NLRP3 inflammasome activation.";
RL Immunity 38:1154-1163(2013).
RN [54]
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 human
RT chemokine decoy receptor CCX-CKR.";
RL J. Biol. Chem. 288:7169-7181(2013).
RN [55]
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).
RN [56]
RP INTERACTION WITH GPR61; GPR62 AND GPR135.
RX PubMed=28827538; DOI=10.1038/s41598-017-08996-7;
RA Oishi A., Karamitri A., Gerbier R., Lahuna O., Ahmad R., Jockers R.;
RT "Orphan GPR61, GPR62 and GPR135 receptors and the melatonin MT2 receptor
RT reciprocally modulate their signaling functions.";
RL Sci. Rep. 7:8990-8990(2017).
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 p53/TP53-mediated apoptosis by regulating MDM2 and reducing
CC the MDM2-mediated degradation of p53/TP53. May serve as nuclear
CC messenger 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-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 IL8-mediated
CC granule release in neutrophils. Involved in the internalization of the
CC atypical chemokine receptor ACKR3. Acts as an adapter protein coupling
CC FFAR4 receptor to specific downstream signaling pathways, as well as
CC mediating receptor endocytosis (PubMed:22282525, PubMed:23809162).
CC During the activation step of NLRP3 inflammasome, directly associates
CC with NLRP3 leading to inhibition of pro-inflammatory cytokine release
CC and inhibition of inflammation (PubMed:23809162).
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:22282525, ECO:0000269|PubMed:22457824,
CC ECO:0000269|PubMed:23809162}.
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 KIR2DL1,
CC KIR2DL3 and KIR2DL4. Interacts with LDLR. Interacts with AP2B1.
CC Interacts with C5AR1. Interacts with RAF1. Interacts with MAP2K1.
CC Interacts with MAPK1. Interacts with MAPK10; the interaction enhances
CC MAPK10 activation by MAP3K5. Interacts with MAP2K4; the interaction is
CC enhanced by presence of MAP3K5 and MAPK10. Interacts with MAP3K5.
CC Interacts with AKT1. Interacts with IKBKB and MAP3K14. Interacts with
CC SMO (activated). Interacts with GSK3A and GSK3B. Associates with
CC protein phosphatase 2A (PP2A) (By similarity). Interacts with DHX8; the
CC interaction is detected in the nucleus upon OR1D2 stimulation.
CC Interacts with GAPDHS; the interaction is detected in the nucleus upon
CC OR1D2 stimulation. Interacts with H2AFX; the interaction is detected in
CC the nucleus upon OR1D2 stimulation. Interacts with KIF14; the
CC interaction is detected in the nucleus upon OR1D2 stimulation.
CC Interacts with RCC1; the interaction is detected in the nucleus upon
CC OR1D2 stimulation. Interacts with CXCR4; the interaction is dependent
CC on C-terminal phosphorylation of CXCR4 and allows activation of MAPK1
CC and MAPK3. Interacts with GPR143. Interacts with HCK and CXCR1
CC (phosphorylated). Interacts with ACKR3 and ACKR4. Interacts with
CC ARRDC1; the interaction is direct (PubMed:23886940). Interacts with
CC GPR61, GPR62 and GPR135 (PubMed:28827538). Interacts (via NACHT and LRR
CC domains) with NLRP3; this interaction is direct and inducible by omega-
CC 3 polyunsaturated fatty acids (PUFAs) (PubMed:23809162). Interacts with
CC FFAR4 (via C-terminus); this interaction is stimulated by long-chain
CC fatty acids (LCFAs) (PubMed:22282525). {ECO:0000250,
CC ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:10973280,
CC ECO:0000269|PubMed:11877451, ECO:0000269|PubMed:12488444,
CC ECO:0000269|PubMed:15125834, ECO:0000269|PubMed:15699339,
CC ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:15888437,
CC ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16319069,
CC ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16516836,
CC ECO:0000269|PubMed:16524428, ECO:0000269|PubMed:16820410,
CC ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:18604210,
CC ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:19782076,
CC ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:22282525,
CC ECO:0000269|PubMed:22300987, ECO:0000269|PubMed:22457824,
CC ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23809162,
CC ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:28827538, ECO:0000305}.
CC -!- INTERACTION:
CC P32121; P07550: ADRB2; NbExp=3; IntAct=EBI-714559, EBI-491169;
CC P32121; P62158: CALM3; NbExp=3; IntAct=EBI-714559, EBI-397435;
CC P32121; P25101: EDNRA; NbExp=2; IntAct=EBI-714559, EBI-6624559;
CC P32121; P06396: GSN; NbExp=3; IntAct=EBI-714559, EBI-351506;
CC P32121; P11142: HSPA8; NbExp=4; IntAct=EBI-714559, EBI-351896;
CC P32121; P06213-1: INSR; NbExp=2; IntAct=EBI-714559, EBI-15558981;
CC P32121; Q99683: MAP3K5; NbExp=2; IntAct=EBI-714559, EBI-476263;
CC P32121; P45984: MAPK9; NbExp=9; IntAct=EBI-714559, EBI-713568;
CC P32121; P19338: NCL; NbExp=3; IntAct=EBI-714559, EBI-346967;
CC P32121; Q14978: NOLC1; NbExp=3; IntAct=EBI-714559, EBI-396155;
CC P32121; Q08499: PDE4D; NbExp=2; IntAct=EBI-714559, EBI-1642831;
CC P32121; Q08499-2: PDE4D; NbExp=2; IntAct=EBI-714559, EBI-8095525;
CC P32121; P14618: PKM; NbExp=4; IntAct=EBI-714559, EBI-353408;
CC P32121; P35813: PPM1A; NbExp=3; IntAct=EBI-714559, EBI-989143;
CC P32121; O75688: PPM1B; NbExp=4; IntAct=EBI-714559, EBI-1047039;
CC P32121; Q13523: PRPF4B; NbExp=3; IntAct=EBI-714559, EBI-395940;
CC P32121; P06702: S100A9; NbExp=2; IntAct=EBI-714559, EBI-1055001;
CC P32121; P12931: SRC; NbExp=2; IntAct=EBI-714559, EBI-621482;
CC P32121; Q15208: STK38; NbExp=3; IntAct=EBI-714559, EBI-458376;
CC P32121; Q13428: TCOF1; NbExp=3; IntAct=EBI-714559, EBI-396105;
CC P32121; P27348: YWHAQ; NbExp=3; IntAct=EBI-714559, EBI-359854;
CC P32121; O95218: ZRANB2; NbExp=4; IntAct=EBI-714559, EBI-1051583;
CC P32121; P31750: Akt1; Xeno; NbExp=3; IntAct=EBI-714559, EBI-298707;
CC P32121; Q9Q2G4: ORF; Xeno; NbExp=3; IntAct=EBI-714559, EBI-6248094;
CC P32121; P40417: rl; Xeno; NbExp=4; IntAct=EBI-714559, EBI-867790;
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 Name=4;
CC IsoId=P32121-4; Sequence=VSP_044697;
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 interaction
CC 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 not
CC regulate internalization and recycling of ADRB2, interaction with
CC clathrin or AP2B1. {ECO:0000269|PubMed:11877451}.
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. {ECO:0000269|PubMed:19363159}.
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.
CC {ECO:0000269|PubMed:21255264}.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Arrestin entry;
CC URL="https://en.wikipedia.org/wiki/Arrestin";
CC ---------------------------------------------------------------------------
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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_001316993.1; NM_001330064.1.
DR RefSeq; NP_004304.1; NM_004313.3. [P32121-1]
DR RefSeq; NP_945355.1; NM_199004.1. [P32121-5]
DR AlphaFoldDB; P32121; -.
DR SMR; P32121; -.
DR BioGRID; 106902; 429.
DR CORUM; P32121; -.
DR DIP; DIP-40089N; -.
DR IntAct; P32121; 340.
DR MINT; P32121; -.
DR STRING; 9606.ENSP00000403701; -.
DR MoonDB; P32121; Curated.
DR MoonProt; P32121; -.
DR TCDB; 8.A.136.1.2; the beta-arrestin (arrb) family.
DR GlyGen; P32121; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P32121; -.
DR PhosphoSitePlus; P32121; -.
DR BioMuta; ARRB2; -.
DR DMDM; 20141230; -.
DR EPD; P32121; -.
DR jPOST; P32121; -.
DR MassIVE; P32121; -.
DR MaxQB; P32121; -.
DR PaxDb; P32121; -.
DR PeptideAtlas; P32121; -.
DR PRIDE; P32121; -.
DR ProteomicsDB; 35156; -.
DR ProteomicsDB; 54838; -. [P32121-1]
DR ProteomicsDB; 54839; -. [P32121-2]
DR ProteomicsDB; 54840; -. [P32121-3]
DR Antibodypedia; 23372; 375 antibodies from 37 providers.
DR DNASU; 409; -.
DR Ensembl; ENST00000269260.7; ENSP00000269260.2; ENSG00000141480.18. [P32121-1]
DR Ensembl; ENST00000346341.6; ENSP00000341895.2; ENSG00000141480.18. [P32121-2]
DR Ensembl; ENST00000381488.10; ENSP00000370898.6; ENSG00000141480.18. [P32121-5]
DR Ensembl; ENST00000412477.7; ENSP00000403701.3; ENSG00000141480.18. [P32121-4]
DR GeneID; 409; -.
DR KEGG; hsa:409; -.
DR MANE-Select; ENST00000269260.7; ENSP00000269260.2; NM_004313.4; NP_004304.1.
DR UCSC; uc002fyj.4; human. [P32121-1]
DR CTD; 409; -.
DR DisGeNET; 409; -.
DR GeneCards; ARRB2; -.
DR HGNC; HGNC:712; ARRB2.
DR HPA; ENSG00000141480; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 107941; gene.
DR neXtProt; NX_P32121; -.
DR OpenTargets; ENSG00000141480; -.
DR PharmGKB; PA60; -.
DR VEuPathDB; HostDB:ENSG00000141480; -.
DR eggNOG; KOG3865; Eukaryota.
DR GeneTree; ENSGT00950000182887; -.
DR HOGENOM; CLU_033484_1_1_1; -.
DR InParanoid; P32121; -.
DR OMA; PHDHIIT; -.
DR OrthoDB; 783081at2759; -.
DR PhylomeDB; P32121; -.
DR TreeFam; TF314260; -.
DR PathwayCommons; P32121; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; P32121; -.
DR SIGNOR; P32121; -.
DR BioGRID-ORCS; 409; 9 hits in 1081 CRISPR screens.
DR ChiTaRS; ARRB2; human.
DR GeneWiki; Arrestin_beta_2; -.
DR GenomeRNAi; 409; -.
DR Pharos; P32121; Tbio.
DR PRO; PR:P32121; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P32121; protein.
DR Bgee; ENSG00000141480; Expressed in granulocyte and 166 other tissues.
DR ExpressionAtlas; P32121; baseline and differential.
DR Genevisible; P32121; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0071889; F:14-3-3 protein binding; IEA:Ensembl.
DR GO; GO:0031691; F:alpha-1A adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0031692; F:alpha-1B adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0031701; F:angiotensin receptor binding; IPI:UniProtKB.
DR GO; GO:1990763; F:arrestin family protein binding; IEA:Ensembl.
DR GO; GO:0031748; F:D1 dopamine receptor binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0031762; F:follicle-stimulating hormone receptor binding; IEA:Ensembl.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IEA:Ensembl.
DR GO; GO:0031859; F:platelet activating factor receptor binding; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0043422; F:protein kinase B binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IEA:Ensembl.
DR GO; GO:0031826; F:type 2A serotonin receptor binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
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 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:0007212; P:dopamine receptor signaling pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; NAS:ParkinsonsUK-UCL.
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:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; NAS:ParkinsonsUK-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl.
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:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IEA:Ensembl.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
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: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:0006366; P:transcription by RNA polymerase II; 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; 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..409
FT /note="Beta-arrestin-2"
FT /id="PRO_0000205199"
FT REGION 240..409
FT /note="Interaction with TRAF6"
FT /evidence="ECO:0000269|PubMed:16378096"
FT REGION 363..409
FT /note="Interaction with AP2B1"
FT MOTIF 385..395
FT /note="[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif"
FT MOD_RES 48
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q91YI4"
FT MOD_RES 176
FT /note="Hydroxyproline; by PHD2"
FT /evidence="ECO:0000269|PubMed:21255264"
FT MOD_RES 181
FT /note="Hydroxyproline; by PHD2"
FT /evidence="ECO:0000269|PubMed:21255264"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29067"
FT MOD_RES 382
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11877451"
FT VAR_SEQ 39..53
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008194"
FT VAR_SEQ 119
FT /note="T -> TVRMPLPSEGQGAGAGTVSGVG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044697"
FT VAR_SEQ 360
FT /note="S -> SAPTPTPPLPVPP (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_008195"
FT MUTAGEN 11
FT /note="K->A: Abolishes interaction with CHUK; when
FT associated with A-12; A-230 and A-231."
FT MUTAGEN 12
FT /note="K->A: Abolishes interaction with CHUK; when
FT associated with A-11; A-230 and A-231."
FT MUTAGEN 54
FT /note="V->A: Inhibits internalization of CXCR4; no effect
FT on interaction with CXCR4."
FT /evidence="ECO:0000269|PubMed:10644702"
FT MUTAGEN 230
FT /note="K->A: Abolishes interaction with CHUK; when
FT associated with A-11; A-12 and A-231."
FT MUTAGEN 231
FT /note="K->A: Abolishes interaction with CHUK; when
FT associated with A-11; A-12 and A-230."
FT MUTAGEN 360
FT /note="S->A,D: Reduces interaction with CHUK; when
FT associated with A-382."
FT MUTAGEN 382
FT /note="T->A,D: Reduces interaction with CHUK; when
FT associated with A-360."
FT /evidence="ECO:0000269|PubMed:11877451"
FT MUTAGEN 382
FT /note="T->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:11877451"
FT CONFLICT 13
FT /note="S -> P (in Ref. 5; BAG59672)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="R -> P (in Ref. 1; CAA77577)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="H -> R (in Ref. 3; ABG47460)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="L -> P (in Ref. 6; CAG29306)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="D -> G (in Ref. 5; BAG59672)"
FT /evidence="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
