Reviewed, UniProtKB/Swiss-Prot P32121 (ARRB2_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	ARRB2
Synonyms:	ARB2, ARR2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	409 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.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43
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. Interacts with DHX8; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with GAPDHS; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with H2AFX; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with KIF14; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with RCC1; the interaction is detected in the nucleus upon OR1D2 stimulation. Ref.12 Ref.15 Ref.16 Ref.23 Ref.25 Ref.27 Ref.31 Ref.36 Ref.37 Ref.38 Ref.40 Ref.26 Ref.32 Ref.34 Ref.44
Subcellular location	Cytoplasm. Nucleus. Cell membrane. Membrane › clathrin-coated pit By similarity. Cytoplasmic vesicle. Note: Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs. Ref.15 Ref.19 Ref.23 Ref.36 Ref.38 Ref.26 Ref.11 Ref.13 Ref.14
Domain	The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1 By similarity.
Post-translational modification	Phosphorylated at Thr-382 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1. 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. Ref.25 Ref.39 Ref.44
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
Coding sequence diversity	Alternative splicing
Molecular function	Signal transduction inhibitor
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor internalization Ref.12 Ref.17 Inferred from direct assay. Source: UniProtKB cell chemotaxis Ref.29 Inferred from mutant phenotype. Source: UniProtKB desensitization of G-protein coupled receptor protein signaling pathway by arrestin Ref.17 Inferred from mutant phenotype. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Ref.23 Ref.37 Inferred from direct assay. Source: UniProtKB negative regulation of natural killer cell mediated cytotoxicity Ref.40 Inferred from mutant phenotype. Source: UniProtKB negative regulation of protein ubiquitination Ref.37 Inferred from direct assay. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Ref.12 Ref.17 Inferred from direct assay. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Ref.25 Inferred from mutant phenotype. Source: UniProtKB sensory perception Inferred from electronic annotation. Source: InterPro transcription from RNA polymerase II promoter Ref.36 Inferred from direct assay. Source: UniProtKB transforming growth factor beta receptor signaling pathway Ref.19 Inferred from direct assay. Source: UniProtKB
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 Ref.40 Inferred from direct assay. Source: UniProtKB
Molecular function	angiotensin receptor binding Inferred from physical interaction. Source: UniProtKB ubiquitin protein ligase binding Ref.25 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AP3B1	O00203	1	EBI-714559,EBI-1044383
ARRB1	P49407	1	EBI-714559,EBI-743313
BOP1	Q14137	1	EBI-714559,EBI-1050828
CALM1	P62158	1	EBI-714559,EBI-397435
DDX27	Q96GQ7	1	EBI-714559,EBI-722051
FBL	P22087	1	EBI-714559,EBI-358318
GSN	P06396	1	EBI-714559,EBI-351506
HSPA8	P11142	1	EBI-714559,EBI-351896
KPNA3	O00505	1	EBI-714559,EBI-358297
KPNA4	O00629	1	EBI-714559,EBI-396343
MRPL43	Q8N983	1	EBI-714559,EBI-1043145
MRPL44	Q9H9J2	1	EBI-714559,EBI-713619
NCL	P19338	1	EBI-714559,EBI-352553
NOLC1	Q14978	2	EBI-714559,EBI-396155
PES1	O00541	1	EBI-714559,EBI-1053271
PKM2	P14618	1	EBI-714559,EBI-353408
PPM1A	P35813	1	EBI-714559,EBI-989143
PPM1B	O75688	1	EBI-714559,EBI-1047039
PRPF4B	Q13523	1	EBI-714559,EBI-395940
RAB5C	P51148	1	EBI-714559,EBI-1054923
RPL7L1	Q6DKI1	1	EBI-714559,EBI-1052408
S100A9	P06702	1	EBI-714559,EBI-1055001
STK38	Q15208	1	EBI-714559,EBI-458376
TCOF1	Q13428	2	EBI-714559,EBI-396105
YWHAQ	P27348	1	EBI-714559,EBI-359854
ZRANB2	O95218	1	EBI-714559,EBI-1051583

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P32121-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P32121-3)

The sequence of this isoform differs from the canonical sequence as follows:
     360-360: S → SAPTPTPPLPVPP

Isoform 3 (identifier: P32121-2)

The sequence of this isoform differs from the canonical sequence as follows:
     39-53: Missing.
     360-360: S → SAPTPTPPLPVPP

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 409	409	Beta-arrestin-2		PRO_0000205199
Regions
	Region	240 – 409	170	Interaction with TRAF6
	Region	363 – 409	47	Interaction with AP2B1
	Motif	385 – 395	11	[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif
Amino acid modifications
	Modified residue	48	1	Phosphotyrosine By similarity
	Modified residue	382	1	Phosphothreonine Ref.15
Natural variations
	Alternative sequence	39 – 53	15	Missing in isoform 3.		VSP_008194
	Alternative sequence	360	1	S → SAPTPTPPLPVPP in isoform 2 and isoform 3.		VSP_008195
Experimental info
	Mutagenesis	11	1	K → A: Abolishes interaction with CHUK; when associated with A-12; A-230 and A-231.
	Mutagenesis	12	1	K → A: Abolishes interaction with CHUK; when associated with A-11; A-230 and A-231.
	Mutagenesis	54	1	V → A: Inhibits internalization of CXCR4; no effect on interaction with CXCR4. Ref.12
	Mutagenesis	230	1	K → A: Abolishes interaction with CHUK; when associated with A-11; A-12 and A-231.
	Mutagenesis	231	1	K → A: Abolishes interaction with CHUK; when associated with A-11; A-12 and A-230.
	Mutagenesis	360	1	S → A or D: Reduces interaction with CHUK; when associated with A-382.
	Mutagenesis	382	1	T → A or D: Reduces interaction with CHUK; when associated with A-360. Ref.15
	Mutagenesis	382	1	T → A: Loss of phosphorylation. Ref.15
	Sequence conflict	189	1	R → P in CAA77577. Ref.1
	Sequence conflict	190	1	H → R in ABG47460. Ref.3
	Sequence conflict	192	1	L → P in CAG29306. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 5, 2002. Version 2. Checksum: DEEC507D4A7B84FF	FASTA	409	46,106
	10 20 30 40 50 60 MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTC 70 80 90 100 110 120 AFRYGREDLD VLGLSFRKDL FIATYQAFPP VPNPPRPPTR LQDRLLRKLG QHAHPFFFTI 130 140 150 160 170 180 PQNLPCSVTL QPGPEDTGKA CGVDFEIRAF CAKSLEEKSH KRNSVRLVIR KVQFAPEKPG 190 200 210 220 230 240 PQPSAETTRH FLMSDRSLHL EASLDKELYY HGEPLNVNVH VTNNSTKTVK KIKVSVRQYA 250 260 270 280 290 300 DICLFSTAQY KCPVAQLEQD DQVSPSSTFC KVYTITPLLS DNREKRGLAL DGKLKHEDTN 310 320 330 340 350 360 LASSTIVKEG ANKEVLGILV SYRVKVKLVV SRGGDVSVEL PFVLMHPKPH DHIPLPRPQS 370 380 390 400 AAPETDVPVD TNLIEFDTNY ATDDDIVFED FARLRLKGMK DDDYDDQLC
	Isoform 2. Checksum: 1D5F728967E2BF5D	FASTA	421	47,271
	10 20 30 40 50 60 MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTC 70 80 90 100 110 120 AFRYGREDLD VLGLSFRKDL FIATYQAFPP VPNPPRPPTR LQDRLLRKLG QHAHPFFFTI 130 140 150 160 170 180 PQNLPCSVTL QPGPEDTGKA CGVDFEIRAF CAKSLEEKSH KRNSVRLVIR KVQFAPEKPG 190 200 210 220 230 240 PQPSAETTRH FLMSDRSLHL EASLDKELYY HGEPLNVNVH VTNNSTKTVK KIKVSVRQYA 250 260 270 280 290 300 DICLFSTAQY KCPVAQLEQD DQVSPSSTFC KVYTITPLLS DNREKRGLAL DGKLKHEDTN 310 320 330 340 350 360 LASSTIVKEG ANKEVLGILV SYRVKVKLVV SRGGDVSVEL PFVLMHPKPH DHIPLPRPQS 370 380 390 400 410 420 APTPTPPLPV PPAAPETDVP VDTNLIEFDT NYATDDDIVF EDFARLRLKG MKDDDYDDQL C
	Isoform 3. Checksum: 2020CE75484DF687	FASTA	406	45,557
	10 20 30 40 50 60 MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVVF VTLTCAFRYG REDLDVLGLS 70 80 90 100 110 120 FRKDLFIATY QAFPPVPNPP RPPTRLQDRL LRKLGQHAHP FFFTIPQNLP CSVTLQPGPE 130 140 150 160 170 180 DTGKACGVDF EIRAFCAKSL EEKSHKRNSV RLVIRKVQFA PEKPGPQPSA ETTRHFLMSD 190 200 210 220 230 240 RSLHLEASLD KELYYHGEPL NVNVHVTNNS TKTVKKIKVS VRQYADICLF STAQYKCPVA 250 260 270 280 290 300 QLEQDDQVSP SSTFCKVYTI TPLLSDNREK RGLALDGKLK HEDTNLASST IVKEGANKEV 310 320 330 340 350 360 LGILVSYRVK VKLVVSRGGD VSVELPFVLM HPKPHDHIPL PRPQSAPTPT PPLPVPPAAP 370 380 390 400 ETDVPVDTNL IEFDTNYATD DDIVFEDFAR LRLKGMKDDD YDDQLC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a member of the arrestin family from a human thyroid cDNA library." Rapoport B., Kaufman K.D., Chamenbalk G.D. Mol. Cell. Endocrinol. 84:R39-R43(1992) [PubMed: 1587386] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Thyroid.
[2]	"G-protein coupled receptor interaction with beta-arrestin 2 through specific agonist stimulation." Yu Q.M., Zhou T.H., Wu Y.L., Cheng Z.J., Ma L., Pei G. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"A new splice-variant of beta-arrestin 2 is involved in agonist-induced MC1R endocytosis." Sanchez-Laorden B.L., Jimenez-Cervantes C., Garcia-Borron J.C. Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Isolation of cDNA coding for human arrestin, beta 2 (ARRB2), transcript variant 1." Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lung.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Testis.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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] (ISOFORM 1). Tissue: Muscle and Pancreas.
[11]	"A beta-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation." Barak L.S., Ferguson S.S.G., Zhang J., Caron M.G. J. Biol. Chem. 272:27497-27500(1997) [PubMed: 9346876] [Abstract] Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH GPCRS.
[12]	"beta-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4." Cheng Z.J., Zhao J., Sun Y., Hu W., Wu Y.L., Cen B., Wu G.-X., Pei G. J. Biol. Chem. 275:2479-2485(2000) [PubMed: 10644702] [Abstract] Cited for: FUNCTION IN IN INTERNALIZATION OF CXCR4, INTERACTION WITH CXCR4, MUTAGENESIS OF VAL-54.
[13]	"Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors." Oakley R.H., Laporte S.A., Holt J.A., Caron M.G., Barak L.S. J. Biol. Chem. 275:17201-17210(2000) [PubMed: 10748214] [Abstract] Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH ANTAGONIST-STIMULATED GPCRS.
[14]	"Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis*." Oakley R.H., Laporte S.A., Holt J.A., Barak L.S., Caron M.G. J. Biol. Chem. 276:19452-19460(2001) [PubMed: 11279203] [Abstract] Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH ANTAGONIST-STIMULATED GPCRS.
[15]	"Regulation of arrestin-3 phosphorylation by casein kinase II." Kim Y.-M., Barak L.S., Caron M.G., Benovic J.L. J. Biol. Chem. 277:16837-16846(2002) [PubMed: 11877451] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF ADBR2, PHOSPHORYLATION AT THR-382, INTERACTION WITH AP2B1; CLATHRIN AND SRC, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-382.
[16]	"Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2." Wang P., Gao H., Ni Y., Wang B., Wu Y., Ji L., Qin L., Ma L., Pei G. J. Biol. Chem. 278:6363-6370(2003) [PubMed: 12488444] [Abstract] Cited for: FUNCTION IN TP53-MEDIATED APOPTOSIS, INTERACTION WITH MDM2.
[17]	"Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference." Ahn S., Nelson C.D., Garrison T.R., Miller W.E., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 100:1740-1744(2003) [PubMed: 12582207] [Abstract] Cited for: FUNCTION IN DESENSITIZATION OF ADRB2, FUNCTION IN INTERNALIZATION OF ADRB2, FUNCTION IN INTERNALIZATION OF AGTR1, FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
[18]	"Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2." Wei H., Ahn S., Shenoy S.K., Karnik S.S., Hunyady L., Luttrell L.M., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 100:10782-10787(2003) [PubMed: 12949261] [Abstract] Cited for: FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
[19]	"Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling." Chen W., Kirkbride K.C., How T., Nelson C.D., Mo J., Frederick J.P., Wang X.-F., Lefkowitz R.J., Blobe G.C. Science 301:1394-1397(2003) [PubMed: 12958365] [Abstract] Cited for: FUNCTION IN ENDOCYTOSIS OF TGFBR2 AND TGFBR3, FUNCTION IN TGF-BETA SIGNALING, SUBCELLULAR LOCATION.
[20]	"Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2." Ahn S., Wei H., Garrison T.R., Lefkowitz R.J. J. Biol. Chem. 279:7807-7811(2004) [PubMed: 14711824] [Abstract] Cited for: FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
[21]	"Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7." Kohout T.A., Nicholas S.L., Perry S.J., Reinhart G., Junger S., Struthers R.S. J. Biol. Chem. 279:23214-23222(2004) [PubMed: 15054093] [Abstract] Cited for: FUNCTION IN CCR7-MEDIATED ERK SIGNALING.
[22]	"Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor." Ahn S., Shenoy S.K., Wei H., Lefkowitz R.J. J. Biol. Chem. 279:35518-35525(2004) [PubMed: 15205453] [Abstract] Cited for: FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
[23]	"Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways." Gao H., Sun Y., Wu Y., Luan B., Wang Y., Qu B., Pei G. Mol. Cell 14:303-317(2004) [PubMed: 15125834] [Abstract] Cited for: FUNCTION IN REGULATION OF NF-KAPPA-B, SUBCELLULAR LOCATION, INTERACTION WITH CHUK AND RELA.
[24]	"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: FUNCTION IN INTERNALIZATION OF SMO.
[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, INTERACTION WITH IGF1R AND MDM2.
[26]	"Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2." Willoughby E.A., Collins M.K. J. Biol. Chem. 280:25651-25658(2005) [PubMed: 15888437] [Abstract] Cited for: INTERACTION WITH DUSP16, SUBCELLULAR LOCATION.
[27]	"G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers." Huettenrauch F., Pollok-Kopp B., Oppermann M. J. Biol. Chem. 280:37503-37515(2005) [PubMed: 16144840] [Abstract] Cited for: FUNCTION IN IN INTERNALIZATION OF CCR5, INTERACTION WITH CCR5.
[28]	"Multiple independent functions of arrestins in the regulation of protease-activated receptor-2 signaling and trafficking." Stalheim L., Ding Y., Gullapalli A., Paing M.M., Wolfe B.L., Morris D.R., Trejo J. Mol. Pharmacol. 67:78-87(2005) [PubMed: 15475570] [Abstract] Cited for: FUNCTION IN F2LR1-MEDIATED ERK SIGNALING.
[29]	"Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxis." Hunton D.L., Barnes W.G., Kim J., Ren X.-R., Violin J.D., Reiter E., Milligan G., Patel D.D., Lefkowitz R.J. Mol. Pharmacol. 67:1229-1236(2005) [PubMed: 15635042] [Abstract] Cited for: FUNCTION IN AGTR1-MEDIATED CHEMOTAXIS.
[30]	"Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor." Ren X.-R., Reiter E., Ahn S., Kim J., Chen W., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 102:1448-1453(2005) [PubMed: 15671180] [Abstract] Cited for: FUNCTION IN AVPR2-MEDIATED ERK SIGNALING.
[31]	"beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform." Szabo E.Z., Numata M., Lukashova V., Iannuzzi P., Orlowski J. Proc. Natl. Acad. Sci. U.S.A. 102:2790-2795(2005) [PubMed: 15699339] [Abstract] Cited for: FUNCTION IN ENDOCYTOSIS OF SLC9A5, INTERACTION WITH SLC9A5.
[32]	"Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly." Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M., Roth R., Heuser J.E., Owen D.J., Traub L.M. Dev. Cell 10:329-342(2006) [PubMed: 16516836] [Abstract] Cited for: INTERACTION WITH AP2B1.
[33]	"beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor." Shenoy S.K., Drake M.T., Nelson C.D., Houtz D.A., Xiao K., Madabushi S., Reiter E., Premont R.T., Lichtarge O., Lefkowitz R.J. J. Biol. Chem. 281:1261-1273(2006) [PubMed: 16280323] [Abstract] Cited for: FUNCTION IN ADRB2-MEDIATED ERK SIGNALING.
[34]	"A beta-arrestin binding determinant common to the second intracellular loops of rhodopsin family G protein-coupled receptors." Marion S., Oakley R.H., Kim K.-M., Caron M.G., Barak L.S. J. Biol. Chem. 281:2932-2938(2006) [PubMed: 16319069] [Abstract] Cited for: INTERACTION WITH HTR2C.
[35]	"Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation." Gesty-Palmer D., Chen M., Reiter E., Ahn S., Nelson C.D., Wang S., Eckhardt A.E., Cowan C.L., Spurney R.F., Luttrell L.M., Lefkowitz R.J. J. Biol. Chem. 281:10856-10864(2006) [PubMed: 16492667] [Abstract] Cited for: FUNCTION IN PTH1R-MEDIATED ERK SIGNALING.
[36]	"Novel function of beta-arrestin2 in the nucleus of mature spermatozoa." Neuhaus E.M., Mashukova A., Barbour J., Wolters D., Hatt H. J. Cell Sci. 119:3047-3056(2006) [PubMed: 16820410] [Abstract] Cited for: FUNCTION IN THE NUCLEUS OF SPERMATOZOA, SUBCELLULAR LOCATION, INTERACTION WITH DHX8; GAPDHS; H2AFX; KIF14 AND RCC1.
[37]	"Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling." Wang Y., Tang Y., Teng L., Wu Y., Zhao X., Pei G. Nat. Immunol. 7:139-147(2006) [PubMed: 16378096] [Abstract] Cited for: FUNCTION IN TLR/IL-1 RECEPTOR SIGNALING, INTERACTION WITH TRAF6.
[38]	"The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells." Lee N.Y., Blobe G.C. J. Biol. Chem. 282:21507-21517(2007) [PubMed: 17540773] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF ENG, FUNCTION IN TGF-BETA-MEDIATED ERK SIGNALING, SUBCELLULAR LOCATION, INTERACTION WITH ENG.
[39]	"Post-endocytic fates of delta-opioid receptor are regulated by GRK2-mediated receptor phosphorylation and distinct beta-arrestin isoforms." Zhang X., Wang F., Chen X., Chen Y., Ma L. J. Neurochem. 106:781-792(2008) [PubMed: 18419762] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF OPRD1, FUNCTION IN DEGRADATION OF OPRD1.
[40]	"An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells." Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H., Sun L., Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., Pei G., Ge B.-X. Nat. Immunol. 9:898-907(2008) [PubMed: 18604210] [Abstract] Cited for: FUNCTION IN REGULATION OF INNATE IMMUNE RESPONSE, INTERACTION WITH KIR2DL1; KIR2DL3 AND KIR2DL4.
[41]	"The type III transforming growth factor-beta receptor negatively regulates nuclear factor kappa B signaling through its interaction with beta-arrestin2." You H.J., How T., Blobe G.C. Carcinogenesis 30:1281-1287(2009) [PubMed: 19325136] [Abstract] Cited for: FUNCTION IN TGFBR3-MEDIATED NF-KAPPA-B REGULATION.
[42]	"Inhibition of dynamin prevents CCL2-mediated endocytosis of CCR2 and activation of ERK1/2." Garcia Lopez M.A., Aguado Martinez A., Lamaze C., Martinez-Alonso C., Fischer T. Cell. Signal. 21:1748-1757(2009) [PubMed: 19643177] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF CCR2.
[43]	"An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages." Cheung R., Malik M., Ravyn V., Tomkowicz B., Ptasznik A., Collman R.G. J. Leukoc. Biol. 86:833-845(2009) [PubMed: 19620252] [Abstract] Cited for: FUNCTION IN MIP-1-BETA-STIMULATED CHEMOTAXIS.
[44]	"Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2." Shenoy S.K., Modi A.S., Shukla A.K., Xiao K., Berthouze M., Ahn S., Wilkinson K.D., Miller W.E., Lefkowitz R.J. Proc. Natl. Acad. Sci. U.S.A. 106:6650-6655(2009) [PubMed: 19363159] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP33, INTERACTION WITH USP33.
+	Additional computationally mapped references.

Web resources

Wikipedia

Arrestin entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z11501 mRNA. Translation: CAA77577.1. AF106941 mRNA. Translation: AAC99468.1. DQ664180 mRNA. Translation: ABG47460.1. EU883572 mRNA. Translation: ACG60646.1. AK097542 mRNA. Translation: BAC05094.1. CR450310 mRNA. Translation: CAG29306.1. DQ314866 Genomic DNA. Translation: ABC40725.1. AC091153 Genomic DNA. No translation available. CH471108 Genomic DNA. Translation: EAW90421.1. BC007427 mRNA. Translation: AAH07427.1. BC067368 mRNA. Translation: AAH67368.1.
IPI	IPI00180375. IPI00783893. IPI00786904.
PIR	S18984.
RefSeq	NP_004304.1. NP_945355.1.
UniGene	Hs.435811
3D structure databases
SMR	P32121. Positions 6-393.
ModBase	Search...
Protein-protein interaction databases
IntAct	P32121. 277 interactions.
STRING	P32121.
PTM databases
PhosphoSite	P32121.
Proteomic databases
PRIDE	P32121.
Genome annotation databases
Ensembl	ENST00000269260; ENSP00000269260; ENSG00000141480; Homo sapiens. [Genome view] ENST00000381488; ENSP00000370898; ENSG00000141480; Homo sapiens. [Genome view]
GeneID	409.
KEGG	hsa:409.
UCSC	uc002fyj.1. human. uc002fyl.1. human. uc002fym.1. human.
Organism-specific databases
CTD	409.
GeneCards	GC17P004560.
HGNC	HGNC:712. ARRB2.
MIM	107941. gene.
PharmGKB	PA60.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07185.
HOVERGEN	P32121.
PhylomeDB	P32121.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6arrestinpathway. Arf6 mediated densensitization of LHCGR. arf6cyclingpathway. Arf6 signaling events. arf6_traffickingpathway. Arf6 trafficking events. nfkappabatypicalpathway. Atypical NF-kappaB pathway. hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins. hedgehog_2pathway. Signaling events mediated by the Hedgehog family. tgfbrpathway. TGF-beta receptor signaling. txa2pathway. Thromboxane A2 receptor signaling.
Gene expression databases
ArrayExpress	P32121.
Bgee	P32121.
CleanEx	HS_ARRB2.
Genevestigator	P32121.
GermOnline	ENSG00000141480. Homo sapiens.
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	1719.
SOURCE	Search...

Entry information

Entry name

ARRB2_HUMAN

Accession

Primary (citable) accession number: P32121
Secondary accession number(s): B5B0C0 , B7WPL3, Q0Z8D3, Q2PP19, Q6ICT3, Q8N7Y2, Q9UEQ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	March 5, 2002
Last modified:	February 9, 2010
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.