Reviewed, UniProtKB/Swiss-Prot P29067 (ARRB2_RAT)

Names and origin

Protein names

Recommended name:
    Beta-arrestin-2
Alternative name(s):
    Arrestin beta-2

Gene names

Name:

Arrb2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	410 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adaptor protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phopshorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors others than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires ADRBK1. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistence by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Ref.6 Ref.8 Ref.11 Ref.13 Ref.17 Ref.18 Ref.25 Ref.28 Ref.29 Ref.30
Subunit structure	Homooligomer; the self-association is mediated by InsP6-binding Probable. Heterooligomer with ARRB1; the association is mediated by InsP6-binding. Interacts with ADRB2 AND CHRM2. Interacts with PDE4A. Interacts with PDE4D. Interacts with MAPK10, MAPK1 and MAPK3. Interacts with DRD2. Interacts with FSHR. Interacts with CLTC. Interacts with HTR2C. Interacts with CCR5. Interacts with CXCR4. Interacts with SRC. Interacts with DUSP16; the interaction is interrupted by stimulation of AGTR1 and activation of MAPK10. Interacts with CHUK; the interaction is enhanced stimulation of ADRB2. Interacts with RELA. Interacts with MDM2; the interaction is enhanced by activation of GPCRs. Interacts with SLC9A5. Interacts with TRAF6. Interacts with IGF1R. Interacts with ENG. Interacts with KIR2DL1, KIR2DL3 and KIR2DL4. Interacts with LDLR. Interacts with AP2B1. Interacts with C5AR1. Interacts with RAF1. Interacts with MAP2K1. Interacts with MAPK1. Interacts with MAPK10; the interaction enhances MAPK10 activation by MAP3K5. Interacts with MAP2K4; the interaction is enhanced by presence of MAP3K5 and MAPK10. Interacts with MAP3K5. Interacts with AKT1. Interacts with IKBKB and MAP3K14. Interacts with SMO (activated). Interacts with GSK3A and GSK3B. Associates with protein phosphatase 2A (PP2A) By similarity. Ref.6 Ref.11 Ref.13 Ref.18 Ref.29 Ref.5 Ref.7 Ref.9 Ref.12 Ref.14 Ref.15 Ref.16 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.26
Subcellular location	Cytoplasm. Nucleus By similarity. Cell membrane. Membrane › clathrin-coated pit. Cytoplasmic vesicle By similarity. Note: Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs. Ref.6 Ref.18 Ref.9 Ref.10
Tissue specificity	Predominantly localized in neuronal tissues and in the spleen.
Post-translational modification	Phosphorylated at Thr-383 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1 By similarity. Ref.15 The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occurr GPCR-specifc. Ubiquitinated by MDM2; the ubiquitination is required for rapid internalization of ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a dissociation of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such as ADRB2, induces transient ubiquitination and subsequently promotes association with USP33. Stimulation of a class B GPCR promotes a sustained ubiquitination By similarity. Ref.25 Ref.14 Ref.24 Ref.27
Sequence similarities	Belongs to the arrestin family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell membrane Coated pit Cytoplasm Cytoplasmic vesicle Membrane Nucleus
Molecular function	Signal transduction inhibitor
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from direct assay. Source: RGD desensitization of G-protein coupled receptor protein signaling pathway by arrestin Traceable author statement. Source: RGD endocytosis Inferred from direct assay. Source: RGD protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of cAMP biosynthetic process Traceable author statement. Source: RGD regulation of cAMP catabolic process Traceable author statement. Source: RGD sensory perception Inferred from electronic annotation. Source: InterPro
Cellular component	coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Ref.1 Inferred from direct assay. Source: RGD
Molecular function	G-protein-coupled receptor binding Traceable author statement. Source: RGD clathrin binding Traceable author statement. Source: RGD protein domain specific binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKT1	P31749	2	EBI-1636616,EBI-296087	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 410	410	Beta-arrestin-2		PRO_0000205201
Regions
	Region	241 – 410	170	Interaction with TRAF6 By similarity
	Region	378 – 410	33	Interaction with AP2B1
	Motif	386 – 396	11	[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif By similarity
Amino acid modifications
	Modified residue	48	1	Phosphotyrosine By similarity
	Modified residue	361	1	Phosphoserine Ref.15
	Modified residue	383	1	Phosphothreonine; by CaMK2 Probable
Experimental info
	Mutagenesis	11 – 12	2	KK → RR: Transient ubiquitination; no stable endocytic complexes with AGTR1; impaired in scaffolding-activated ERK1/2. Ref.24
	Mutagenesis	18	1	K → R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-107, R-108, R-207 and R-296. Ref.30 Ref.24
	Mutagenesis	54	1	V → A: Inhibits internalization of EDNRA and EDNRB. Ref.8 Ref.24
	Mutagenesis	107	1	K → R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-108, R-207 and R-296. Ref.30 Ref.24
	Mutagenesis	108	1	K → R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-107, R-207 and R-296. Ref.30 Ref.24
	Mutagenesis	198	1	S → P: Greatly reduces interaction with MAPK10. Ref.24
	Mutagenesis	207	1	K → R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-107, R-108 and R-296. Ref.30 Ref.24
	Mutagenesis	296	1	K → R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-107, R-108 and R-207. Ref.30 Ref.24
	Mutagenesis	361	1	S → D: Almost abolishes phosphorylation; inhibits internalization of ADRB2; when associated with D-383. Ref.15 Ref.24
	Mutagenesis	361	1	S → D: Reduces interaction with CLTC. Ref.15 Ref.24
	Mutagenesis	374 – 377	4	LIEF → AAEA: Abolishes interaction with CLTC; reduces interaction with AP2B1. Ref.6 Ref.24
	Mutagenesis	383	1	T → D: Almost abolishes phosphorylation; inhibits internalization of ADRB2; when associated with D-361. Ref.15 Ref.24
	Mutagenesis	383	1	T → D: Reduces interaction with CLTC. Ref.15 Ref.24
	Mutagenesis	394	1	R → A: Abolishes interaction with AP2B1; no effect on interaction with clathrin. Ref.24
	Mutagenesis	396	1	R → A: Abolishes interaction with AP2B1. Ref.9 Ref.24
	Mutagenesis	398	1	K → A: No effect on interaction with AP2B1. Ref.9 Ref.24

Sequences

	Sequence		Length	Mass (Da)
	P29067-1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 0DFA6A897C2B86BA	FASTA	410	46,340
	10 20 30 40 50 60 MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTC 70 80 90 100 110 120 AFRYGREDLD VLGLSFRKDL FIATYQAFPP MPNPPRPPTR LQDRLLKKLG QHAHPFFFTI 130 140 150 160 170 180 PQNLPCSVTL QPGPEDTGKA CGVDFEIRAF CAKSIEEKSH KRNSVRLIIR KVQFAPETPG 190 200 210 220 230 240 PQPSAETTRH FLMSDRRSLH LEASLDKELY YHGEPLNVNV HVTNNSAKTV KKIRVSVRQY 250 260 270 280 290 300 ADICLFSTAQ YKCPVAQLEQ DDQVSPSSTF CKVYTITPLL SDNREKRGLA LDGQLKHEDT 310 320 330 340 350 360 NLASSTIVKE GANKEVLGIL VSYRVKVKLV VSRGGDVSVE LPFVLMHPKP HDHITLPRPQ 370 380 390 400 410 SAPREIDIPV DTNLIEFDTN YATDDDIVFE DFARLRLKGM KDDDCDDQFC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family." Attramadal H., Arriza J.L., Aoki C., Dawson T.M., Codina J., Kwatra M.M., Snyder S.H., Caron M.G., Lefkowitz R.J. J. Biol. Chem. 267:17882-17890(1992) [PubMed: 1517224] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Cone arrestin identified by targeting expression of a functional family." Craft C.M., Whitmore D.H., Wiechmann A.F. J. Biol. Chem. 269:4613-4619(1994) [PubMed: 8308033] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 295-410. Tissue: Pineal gland.
[4]	"Differential expression of alternative splice variants of beta-arrestin-1 and -2 in rat central nervous system and peripheral tissues." Komori N., Cain S.D., Roch J.-M., Miller K.E., Matsumoto H. Eur. J. Neurosci. 10:2607-2616(1998) [PubMed: 9767391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 305-386. Strain: Sprague-Dawley. Tissue: Retina.
[5]	"beta-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor." Lin F.-T., Daaka Y., Lefkowitz R.J. J. Biol. Chem. 273:31640-31643(1998) [PubMed: 9822622] [Abstract] Cited for: INTERACTION WITH IGF1R.
[6]	"The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis." Laporte S.A., Oakley R.H., Zhang J., Holt J.A., Ferguson S.S.G., Caron M.G., Barak L.S. Proc. Natl. Acad. Sci. U.S.A. 96:3712-3717(1999) [PubMed: 10097102] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF ADRB2, INTERACTION WITH CLTC AND AP2B1, MUTAGENESIS OF 374-LEU--PHE-377, SUBCELLULAR LOCATION.
[7]	"beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis." Miller W.E., Maudsley S., Ahn S., Khan K.D., Luttrell L.M., Lefkowitz R.J. J. Biol. Chem. 275:11312-11319(2000) [PubMed: 10753943] [Abstract] Cited for: INTERACTION WITH SRC.
[8]	"Regulation and intracellular trafficking pathways of the endothelin receptors." Bremnes T., Paasche J.D., Mehlum A., Sandberg C., Bremnes B., Attramadal H. J. Biol. Chem. 275:17596-17604(2000) [PubMed: 10747877] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF EDNRA AND EDNRB, MUTAGENESIS OF VAL-54.
[9]	"The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits." Laporte S.A., Oakley R.H., Holt J.A., Barak L.S., Caron M.G. J. Biol. Chem. 275:23120-23126(2000) [PubMed: 10770944] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH AP2B1 AND CLTC, MUTAGENESIS OF ARG-396 AND LYS-398.
[10]	"Selective recruitment of arrestin-3 to clathrin coated pits upon stimulation of G protein-coupled receptors." Santini F., Penn R.B., Gagnon A.W., Benovic J.L., Keen J.H. J. Cell Sci. 113:2463-2470(2000) [PubMed: 10852825] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3." McDonald P.H., Chow C.W., Miller W.E., Laporte S.A., Field M.E., Lin F.-T., Davis R.J., Lefkowitz R.J. Science 290:1574-1577(2000) [PubMed: 11090355] [Abstract] Cited for: FUNCTION IN MAPK SIGNALING, INTERACTION WITH MAPK10; MAP2K4 AND MAP3K5.
[12]	"Characterization of sequence determinants within the carboxyl-terminal domain of chemokine receptor CCR5 that regulate signaling and receptor internalization." Kraft K., Olbrich H., Majoul I., Mack M., Proudfoot A., Oppermann M. J. Biol. Chem. 276:34408-34418(2001) [PubMed: 11448957] [Abstract] Cited for: INTERACTION WITH CCR5.
[13]	"Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds." Luttrell L.M., Roudabush F.L., Choy E.W., Miller W.E., Field M.E., Pierce K.L., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 98:2449-2454(2001) [PubMed: 11226259] [Abstract] Cited for: FUNCTION IN MAPK SIGNALING, INTERACTION WITH RAF1; MAP2K1 AND MAPK1.
[14]	"Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin." Shenoy S.K., McDonald P.H., Kohout T.A., Lefkowitz R.J. Science 294:1307-1313(2001) [PubMed: 11588219] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH MDM2.
[15]	"Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors." Lin F.-T., Chen W., Shenoy S., Cong M., Exum S.T., Lefkowitz R.J. Biochemistry 41:10692-10699(2002) [PubMed: 12186555] [Abstract] Cited for: PHOSPHORYLATION AT SER-361 AND THR-383, INTERACTION WITH CLTC, MUTAGENESIS OF SER-361 AND THR-383.
[16]	"beta-Arrestin/AP-2 interaction in G protein-coupled receptor internalization: identification of a beta-arrestin binding site in beta 2-adaptin." Laporte S.A., Miller W.E., Kim K.-M., Caron M.G. J. Biol. Chem. 277:9247-9254(2002) [PubMed: 11777907] [Abstract] Cited for: INTERACTION WITH AP2B1.
[17]	"beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation." Tohgo A., Pierce K.L., Choy E.W., Lefkowitz R.J., Luttrell L.M. J. Biol. Chem. 277:9429-9436(2002) [PubMed: 11777902] [Abstract] Cited for: FUNCTION IN ERK SIGNALING.
[18]	"Phosphorylation of key serine residues is required for internalization of the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin, dynamin, and clathrin-dependent pathway." Braun L., Christophe T., Boulay F. J. Biol. Chem. 278:4277-4285(2003) [PubMed: 12464600] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF C5AR1, SUBCELLULAR LOCATION, INTERACTION WITH C5AR1.
[19]	"The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor." Wu J.-H., Peppel K., Nelson C.D., Lin F.-T., Kohout T.A., Miller W.E., Exum S.T., Freedman N.J. J. Biol. Chem. 278:44238-44245(2003) [PubMed: 12944399] [Abstract] Cited for: INTERACTION WITH LDLR.
[20]	"The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with beta-arrestins." Bolger G.B., McCahill A., Huston E., Cheung Y.F., McSorley T., Baillie G.S., Houslay M.D. J. Biol. Chem. 278:49230-49238(2003) [PubMed: 14500724] [Abstract] Cited for: INTERACTION WITH PDE4D.
[21]	"beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha." Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004) [PubMed: 15173580] [Abstract] Cited for: INTERACTION WITH CHUK; IKBKB AND MAP3K14.
[22]	"Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2." Chen W., Ren X.R., Nelson C.D., Barak L.S., Chen J.K., Beachy P.A., de Sauvage F., Lefkowitz R.J. Science 306:2257-2260(2004) [PubMed: 15618519] [Abstract] Cited for: INTERACTION WITH SMO.
[23]	"An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior." Beaulieu J.-M., Sotnikova T.D., Marion S., Lefkowitz R.J., Gainetdinov R.R., Caron M.G. Cell 122:261-273(2005) [PubMed: 16051150] [Abstract] Cited for: INTERACTION WITH AKT1; GSK3A AND GSK3B.
[24]	"Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes." Shenoy S.K., Lefkowitz R.J. J. Biol. Chem. 280:15315-15324(2005) [PubMed: 15699045] [Abstract] Cited for: UBIQUITINATION, MUTAGENESIS OF 11-LYS-LYS-12.
[25]	"{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase." Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., Lefkowitz R.J., Larsson O. J. Biol. Chem. 280:24412-24419(2005) [PubMed: 15878855] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF IGF1R.
[26]	"Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene." Wallace D.A., Johnston L.A., Huston E., Macmaster D., Houslay T.M., Cheung Y.-F., Campbell L., Millen J.E., Smith R.A., Gall I., Knowles R.G., Sullivan M., Houslay M.D. Mol. Pharmacol. 67:1920-1934(2005) [PubMed: 15738310] [Abstract] Cited for: INTERACTION WITH PDE4A.
[27]	"Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation." Shenoy S.K., Barak L.S., Xiao K., Ahn S., Berthouze M., Shukla A.K., Luttrell L.M., Lefkowitz R.J. J. Biol. Chem. 282:29549-29562(2007) [PubMed: 17666399] [Abstract] Cited for: UBIQUITINATION.
[28]	"Role of beta-arrestin-mediated desensitization and signaling in the control of angiotensin AT1a receptor-stimulated transcription." Lee M.-H., El-Shewy H.M., Luttrell D.K., Luttrell L.M. J. Biol. Chem. 283:2088-2097(2008) [PubMed: 18006496] [Abstract] Cited for: FUNCTION IN DESENSITIZATION OF AGTR1, FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
[29]	"The beta-arrestin-2 scaffold protein promotes c-Jun N-terminal kinase-3 activation by binding to its nonconserved N terminus." Guo C., Whitmarsh A.J. J. Biol. Chem. 283:15903-15911(2008) [PubMed: 18408005] [Abstract] Cited for: FUNCTION IN MAPK SIGNALING, INTERACTION WITH MAPK10 AND MAP3K5, MUTAGENENESIS OF SER-198.
[30]	"Differential role of beta-arrestin ubiquitination in agonist-promoted down-regulation of M1 vs M2 muscarinic acetylcholine receptors." Mosser V.A., Jones K.T., Hoffman K.M., McCarty N.A., Jackson D.A. J. Mol. Signal. 3:20-20(2008) [PubMed: 19055777] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF CHRM1 AND CHRM2, MUTAGENESIS OF LYS-18; LYS-107; LYS-108; LYS-207 AND LYS-296.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M91590 mRNA. Translation: AAA74460.1. BC087578 mRNA. Translation: AAH87578.1. U03627 mRNA. Translation: AAA17551.1. AF051457 Genomic DNA. Translation: AAC28617.1.
IPI	IPI00231135.
PIR	A59279.
RefSeq	NP_037043.1.
UniGene	Rn.32973
3D structure databases
SMR	P29067. Positions 6-394.
ModBase	Search...
Protein-protein interaction databases
IntAct	P29067. 5 interactions.
STRING	P29067.
PTM databases
PhosphoSite	P29067.
Genome annotation databases
Ensembl	ENSRNOT00000026207; ENSRNOP00000026207; ENSRNOG00000019308; Rattus norvegicus. [Genome view]
GeneID	25388.
KEGG	rno:25388.
UCSC	NM_012911. rat.
Organism-specific databases
CTD	25388.
RGD	2157. Arrb2.
Phylogenomic databases
eggNOG	roNOG09055.
HOVERGEN	P29067.
InParanoid	P29067.
PhylomeDB	P29067.
Gene expression databases
ArrayExpress	P29067.
Genevestigator	P29067.
GermOnline	ENSRNOG00000019308. Rattus norvegicus.
Family and domain databases
InterPro	IPR000698. Arrestin. IPR011022. Arrestin-like_C. IPR011021. Arrestin-like_N. IPR014752. Arrestin_C. IPR017864. Arrestin_CS. IPR014753. Arrestin_N. IPR014756. Ig_E-set. [Graphical view]
Gene3D	G3DSA:2.60.40.640. Arrestin_C. 1 hit. G3DSA:2.60.40.840. Arrestin_N. 1 hit.
PANTHER	PTHR11792. Arrestin. 1 hit.
Pfam	PF02752. Arrestin_C. 1 hit. PF00339. Arrestin_N. 1 hit. [Graphical view]
PRINTS	PR00309. ARRESTIN.
PROSITE	PS00295. ARRESTINS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	606447.

Entry information

Entry name

ARRB2_RAT

Accession

Primary (citable) accession number: P29067

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	February 9, 2010
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)