P49407 (ARRB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-arrestin-1

Alternative name(s):
Arrestin beta-1

Gene names

Name:	ARRB1
Synonyms:	ARR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	418 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 adapter 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. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. 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). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. 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). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. 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. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. 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. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) By similarity. Involved in IL8-mediated granule release in neutrophils. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.29 Ref.32
Subunit structure	Monomer. Homodimer. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB2; the association is mediated by InsP6-binding. Interacts with GPR143. Interacts with ADRB2 (phosphorylated). Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated at 'Tyr-737'); phosphorylation of AP2B1 at 'Tyr-737' disrupts the interaction. Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with CCR2 and ADRBK1. Interacts with CRR5. Interacts with PTAFR (phosphorylated on serine residues). Interacts with CLTC and MAP2K3. Interacts with CREB1. Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and the protein kinase domain); the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with TACR1. Interacts with RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts with DVL1; the interaction is enhanced by phosphorylation of DVL1. Interacts with DVL2; the interaction is enhanced by phosphorylation of DVL2. Interacts with IGF1R. Associates with MAP kinase p38. Part of a MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1 (activated) and MAPK3 (activated). Part of a MAPK signaling complex consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3 (activated) By similarity. Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated). Ref.7 Ref.9 Ref.11 Ref.12 Ref.13 Ref.15 Ref.17 Ref.20 Ref.23 Ref.24 Ref.25 Ref.26 Ref.31 Ref.33
Subcellular location	Cytoplasm. Nucleus. Cell membrane. Membrane › clathrin-coated pit Probable. Cell projection › pseudopodium By similarity. Cytoplasmic vesicle. Note: Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs. The monomeric form is predominantly located in the nucleus. The oligomeric form is located in the cytoplasm. Translocates to the nucleus upon stimulation of OPRD1 By similarity. Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.18 Ref.21 Ref.23
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. Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface. The N-terminus binds InsP6 with low affinity By similarity. The C-terminus binds InsP6 with high affinity By similarity.
Post-translational modification	Constitutively phosphorylated at Ser-412 in the cytoplasm. At the plasma membrane, is rapidly dephosphorylated, a process that is required for clathrin binding and ADRB2 endocytosis but not for ADRB2 binding and desensitization. Once internalized, is rephosphorylated. Ref.30 The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occur GPCR-specific. 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. Ref.33
Sequence similarities	Belongs to the arrestin family.

Ontologies

Keywords
Biological process	Protein transport Transcription Transcription regulation Transport
Cellular component	Cell membrane Cell projection Coated pit Cytoplasm Cytoplasmic vesicle Membrane Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Signal transduction inhibitor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor internalization Inferred from mutant phenotype PubMed 10521508PubMed 12582207. Source: UniProtKB Notch signaling pathway Traceable author statement. Source: Reactome cellular membrane organization Traceable author statement. Source: Reactome negative regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.24. Source: UniProtKB negative regulation of interleukin-6 production Inferred from direct assay Ref.24. Source: UniProtKB negative regulation of interleukin-8 production Inferred from direct assay Ref.24. Source: UniProtKB negative regulation of protein ubiquitination Inferred from direct assay Ref.24. Source: UniProtKB phototransduction Inferred from electronic annotation. Source: Compara platelet activation Traceable author statement. Source: Reactome positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 10644702. Source: UniProtKB positive regulation of Rho protein signal transduction Inferred from mutant phenotype Ref.16. Source: UniProtKB positive regulation of histone H4 acetylation Inferred from mutant phenotype Ref.15. Source: UniProtKB positive regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of protein binding Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.15. Source: BHF-UCL post-Golgi vesicle-mediated transport Traceable author statement. Source: Reactome proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.13. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Inferred from mutant phenotype Ref.13. Source: UniProtKB stress fiber assembly Inferred from mutant phenotype Ref.16. Source: UniProtKB transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.15. Source: UniProtKB
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome chromatin Inferred from direct assay Ref.15. Source: BHF-UCL coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle membrane Traceable author statement. Source: Reactome cytosol Traceable author statement. Source: Reactome lysosomal membrane Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.15. Source: UniProtKB plasma membrane Traceable author statement Ref.9. Source: ProtInc pseudopodium Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GTPase activator activity Inferred from mutant phenotype Ref.16. Source: UniProtKB cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from electronic annotation. Source: Compara enzyme inhibitor activity Traceable author statement PubMed 2163110. Source: ProtInc transcription regulatory region DNA binding Inferred from mutant phenotype Ref.15. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALM3	P62158	3	EBI-743313,EBI-397435
GNMT	Q14749	5	EBI-743313,EBI-744239
GSN	P06396	3	EBI-743313,EBI-351506
HIF1A	Q16665	3	EBI-743313,EBI-447269
HSPA8	P11142	4	EBI-743313,EBI-351896
NCL	P19338	3	EBI-743313,EBI-346967
NOLC1	Q14978	3	EBI-743313,EBI-396155
PKM	P14618	3	EBI-743313,EBI-353408
PPM1A	P35813	4	EBI-743313,EBI-989143
PPM1B	O75688	4	EBI-743313,EBI-1047039
PRPF4B	Q13523	2	EBI-743313,EBI-395940
S100A9	P06702	2	EBI-743313,EBI-1055001
STK38	Q15208	3	EBI-743313,EBI-458376
TCOF1	Q13428	3	EBI-743313,EBI-396105
YWHAQ	P27348	3	EBI-743313,EBI-359854
YY1	P25490	4	EBI-743313,EBI-765538
ZRANB2	O95218	4	EBI-743313,EBI-1051583

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1A (identifier: P49407-1)

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 1B (identifier: P49407-2)

The sequence of this isoform differs from the canonical sequence as follows:
     334-341: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 418

418

Beta-arrestin-1

PRO_0000205194

Regions

Region

1 – 163

163

Interaction with SRC By similarity

Region

45 – 86

42

Interaction with CHRM2 By similarity

Region

318 – 418

101

Interaction with TRAF6

Motif

385 – 395

11

[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif

Sites

Binding site

250

1

Inositol hexakisphosphate By similarity

Binding site

255

1

Inositol hexakisphosphate By similarity

Binding site

324

1

Inositol hexakisphosphate By similarity

Binding site

326

1

Inositol hexakisphosphate By similarity

Amino acid modifications

Modified residue

47

1

Phosphotyrosine By similarity

Modified residue

410

1

Phosphothreonine By similarity

Modified residue

412

1

Phosphoserine; by GRK5 Ref.30 Ref.34 Ref.36

Natural variations

Alternative sequence

334 – 341

8

Missing in isoform 1B.

VSP_000322

Experimental info

Mutagenesis

169

1

R → E: Constitutive active; enables phosphorylation-independent binding to GPCRs. Ref.8

Mutagenesis

388

1

F → A: Abolishes interaction with AP2B1. Ref.20

Mutagenesis

390

1

D → P: Abolishes interaction with AP2B1. Ref.20

Mutagenesis

393

1

R → A: Abolishes interaction with AP2B1. Ref.20

Sequence conflict

146

1

V → A in AAA35559. Ref.1

Sequence conflict

146

1

V → A in AAA35558. Ref.1

Sequence conflict

165

1

R → G in AAA35559. Ref.1

Sequence conflict

165

1

R → G in AAA35558. Ref.1

Sequence conflict

229

1

K → E in AAA35559. Ref.1

Sequence conflict

229

1

K → E in AAA35558. Ref.1

Sequence conflict

329

1

V → E in AAC33295. Ref.2

Sequence conflict

329

1

V → E in AAC34123. Ref.2

Sequence conflict

400

1

K → E in AAA35559. Ref.1

Sequence conflict

400

1

K → E in AAA35558. Ref.1

Sequence conflict

414

1

Q → R in AAA35559. Ref.1

Sequence conflict

414

1

Q → R in AAA35558. Ref.1

Sequence conflict

417

1

N → D in AAA35559. Ref.1

Sequence conflict

417

1

N → D in AAA35558. Ref.1

Secondary structure

1

.

.

.

418

Helix Strand Turn

Details...

Helix

384 – 394

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1A [UniParc]. Last modified March 5, 2002. Version 2. Checksum: 0A3C135092338D10	FASTA	418	47,066
	10 20 30 40 50 60 MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA 70 80 90 100 110 120 FRYGREDLDV LGLTFRKDLF VANVQSFPPA PEDKKPLTRL QERLIKKLGE HAYPFTFEIP 130 140 150 160 170 180 PNLPCSVTLQ PGPEDTGKAC GVDYEVKAFC AENLEEKIHK RNSVRLVIRK VQYAPERPGP 190 200 210 220 230 240 QPTAETTRQF LMSDKPLHLE ASLDKEIYYH GEPISVNVHV TNNTNKTVKK IKISVRQYAD 250 260 270 280 290 300 ICLFNTAQYK CPVAMEEADD TVAPSSTFCK VYTLTPFLAN NREKRGLALD GKLKHEDTNL 310 320 330 340 350 360 ASSTLLREGA NREILGIIVS YKVKVKLVVS RGGLLGDLAS SDVAVELPFT LMHPKPKEEP 370 380 390 400 410 PHREVPENET PVDTNLIELD TNDDDIVFED FARQRLKGMK DDKEEEEDGT GSPQLNNR
	Isoform 1B [UniParc]. Checksum: 4FBA2B09E6C2D236	FASTA	410	46,309
	10 20 30 40 50 60 MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA 70 80 90 100 110 120 FRYGREDLDV LGLTFRKDLF VANVQSFPPA PEDKKPLTRL QERLIKKLGE HAYPFTFEIP 130 140 150 160 170 180 PNLPCSVTLQ PGPEDTGKAC GVDYEVKAFC AENLEEKIHK RNSVRLVIRK VQYAPERPGP 190 200 210 220 230 240 QPTAETTRQF LMSDKPLHLE ASLDKEIYYH GEPISVNVHV TNNTNKTVKK IKISVRQYAD 250 260 270 280 290 300 ICLFNTAQYK CPVAMEEADD TVAPSSTFCK VYTLTPFLAN NREKRGLALD GKLKHEDTNL 310 320 330 340 350 360 ASSTLLREGA NREILGIIVS YKVKVKLVVS RGGDVAVELP FTLMHPKPKE EPPHREVPEN 370 380 390 400 410 ETPVDTNLIE LDTNDDDIVF EDFARQRLKG MKDDKEEEED GTGSPQLNNR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing." Parruti G., Peracchia F., Sallese M., Ambrosini G., Masini M., Rotilio D., de Blasi A. J. Biol. Chem. 268:9753-9761(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B). Tissue: Peripheral blood.
[2]	"Molecular cloning of two isoforms of human beta-arrestin 1." Yu Q.M., Zhou T.H., Cheng Z.J., Ma L., Pei G. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B). Tissue: Brain.
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Isolation of cDNA coding for Homo sapiens arrestin, beta 1 (ARRB1), transcript variant 2." Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1B). Tissue: Lung.
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1A). Tissue: Uterus.
[7]	"Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2." Aragay A.M., Mellado M., Frade J.M., Martin A.M., Jimenez-Sainz M.C., Martinez-A C., Mayor F. Jr. Proc. Natl. Acad. Sci. U.S.A. 95:2985-2990(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CCR2 AND ADRBK1.
[8]	"Targeted construction of phosphorylation-independent beta-arrestin mutants with constitutive activity in cells." Kovoor A., Celver J., Abdryashitov R.I., Chavkin C., Gurevich V.V. J. Biol. Chem. 274:6831-6834(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARG-169.
[9]	"Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes." Luttrell L.M., Ferguson S.S.G., Daaka Y., Miller W.E., Maudsley S., Della Rocca G.J., Lin F.-T., Kawakatsu H., Owada K., Luttrell D.K., Caron M.G., Lefkowitz R.J. Science 283:655-661(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ADRB2, SUBCELLULAR LOCATION.
[10]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH ANTAGONIST-STIMULATED GPCRS.
[11]	"Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI." Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E., Xu L., Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J. Nat. Immunol. 1:227-233(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCK AND CXCR1.
[12]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF C5AR1, SUBCELLULAR LOCATION, INTERACTION WITH C5AR1.
[13]	"{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] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF IGF1R, INTERACTION WITH IGF1R AND MDM2.
[14]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
[15]	"A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription." Kang J., Shi Y., Xiang B., Qu B., Su W., Zhu M., Zhang M., Bao G., Wang F., Zhang X., Yang R., Fan F., Chen X., Pei G., Ma L. Cell 123:833-847(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR FUNCTION IN TRANSCRIPTIONAL REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH CREB1.
[16]	"beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation." Barnes W.G., Reiter E., Violin J.D., Ren X.-R., Milligan G., Lefkowitz R.J. J. Biol. Chem. 280:8041-8050(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CYTOSKELETAL REARRANGEMENT, SUBCELLULAR LOCATION.
[17]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN IN INTERNALIZATION OF CCR5, INTERACTION WITH CCR5.
[18]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN F2LR1-MEDIATED ERK SIGNALING, SUBCELLULAR LOCATION.
[19]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN AVPR2-MEDIATED ERK SIGNALING.
[20]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AP2B1, MUTAGENESIS OF PHE-388; ASP-390 AND ARG-393.
[21]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN ADRB2-MEDIATED ERK SIGNALING, SUBCELLULAR LOCATION.
[22]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN PTH1R-MEDIATED ERK SIGNALING.
[23]	"Platelet-activating factor-induced clathrin-mediated endocytosis requires beta-arrestin-1 recruitment and activation of the p38 MAPK signalosome at the plasma membrane for actin bundle formation." McLaughlin N.J., Banerjee A., Kelher M.R., Gamboni-Robertson F., Hamiel C., Sheppard F.R., Moore E.E., Silliman C.C. J. Immunol. 176:7039-7050(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF PTAFR, FUNCTION IN THE P38 MAPK SIGNALING PATHWAY, FUNCTION IN ACTIN BUNDLE FORMATION, SUBCELLULAR LOCATION, INTERACTION WITH PTAFR AND MAP2K3.
[24]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN TLR/IL-1 RECEPTOR SIGNALING, INTERACTION WITH TRAF6.
[25]	"The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor." Innamorati G., Piccirillo R., Bagnato P., Palmisano I., Schiaffino M.V. Pigment Cell Res. 19:125-135(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPR143.
[26]	"Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2 complex." Fessart D., Simaan M., Zimmerman B., Comeau J., Hamdan F.F., Wiseman P.W., Bouvier M., Laporte S.A. J. Cell Sci. 120:1723-1732(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AP2B1.
[27]	"Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle." Deshpande D.A., Theriot B.S., Penn R.B., Walker J.K. FASEB J. 22:2134-2141(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN BETA-ADRENERGIC RECEPTOR REGULATION.
[28]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF OPRD1.
[29]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN INTERNALIZATION OF CCR2.
[30]	"Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling." Barthet G., Carrat G., Cassier E., Barker B., Gaven F., Pillot M., Framery B., Pellissier L.P., Augier J., Kang D.S., Claeysen S., Reiter E., Baneres J.L., Benovic J.L., Marin P., Bockaert J., Dumuis A. EMBO J. 28:2706-2718(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-412.
[31]	"A scanning peptide array approach uncovers association sites within the JNK/beta arrestin signalling complex." Li X., MacLeod R., Dunlop A.J., Edwards H.V., Advant N., Gibson L.C., Devine N.M., Brown K.M., Adams D.R., Houslay M.D., Baillie G.S. FEBS Lett. 583:3310-3316(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP2K4/MKK4.
[32]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN MIP-1-BETA-STIMULATED CHEMOTAXIS.
[33]	"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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP33, INTERACTION WITH USP33.
[34]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[35]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412, MASS SPECTROMETRY.
[37]	"Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly." Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y., Mills I.G., Benmerah A., McMahon H.T. PLoS Biol. 4:E262-E262(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 383-402 IN COMPLEX WITH AP2B1.
+	Additional computationally mapped references.

Web resources

Wikipedia

Arrestin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L04685 mRNA. Translation: AAA35559.1.
L04685 mRNA. Translation: AAA35558.1.
AF084040 mRNA. Translation: AAC33295.1.
AF084940 mRNA. Translation: AAC34123.1.
DQ314865 Genomic DNA. Translation: ABC40724.1.
FJ348262 mRNA. Translation: ACI96306.1.
CH471076 Genomic DNA. Translation: EAW74962.1.
BC003636 mRNA. Translation: AAH03636.1.

IPI

IPI00293857.
IPI00336017.

PIR

B46682.

RefSeq

NP_004032.2. NM_004041.4.
NP_064647.1. NM_020251.3.

UniGene

Hs.503284.
Hs.625320.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IV8	X-ray	2.80	P/Q	383-402	[»]

ProteinModelPortal

P49407.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29979N.

IntAct

P49407. 187 interactions.

MINT

MINT-128176.

STRING

9606.ENSP00000377141.

PTM databases

PhosphoSite

P49407.

Polymorphism databases

DMDM

20141238.

2D gel databases

OGP

P49407.

Proteomic databases

PaxDb

P49407.

PRIDE

P49407.

Protocols and materials databases

DNASU

408.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360025; ENSP00000353124; ENSG00000137486.
ENST00000420843; ENSP00000409581; ENSG00000137486.

GeneID

408.

KEGG

hsa:408.

UCSC

uc001owe.2. human.
uc001owf.2. human.

Organism-specific databases

CTD

408.

GeneCards

GC11M074976.

HGNC

HGNC:711. ARRB1.

HPA

CAB003763.

MIM

107940. gene.

neXtProt

NX_P49407.

PharmGKB

PA59.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG302111.

HOGENOM

HOG000231319.

HOVERGEN

HBG002399.

InParanoid

P49407.

KO

K04439.

OMA

YKCPVAV.

OrthoDB

EOG4MCX0K.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6cyclingpathway. Arf6 signaling events.

Reactome

REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P49407.

Bgee

P49407.

CleanEx

HS_ARRB1.

Genevestigator

P49407.

GermOnline

ENSG00000137486. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.640. 1 hit.
2.60.40.840. 1 hit.

InterPro

IPR000698. Arrestin.
IPR011021. Arrestin-like_N.
IPR014752. Arrestin_C.
IPR011022. Arrestin_C-like.
IPR017864. Arrestin_CS.
IPR014753. Arrestin_N.
IPR014756. Ig_E-set.
[Graphical view]

PANTHER

PTHR11792. PTHR11792. 1 hit.

Pfam

PF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]

PRINTS

PR00309. ARRESTIN.

SMART

SM01017. Arrestin_C. 1 hit.
[Graphical view]

SUPFAM

SSF81296. Ig_E-set. 2 hits.

PROSITE

PS00295. ARRESTINS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P49407.

ChEMBL

CHEMBL1795088.

EvolutionaryTrace

P49407.

GenomeRNAi

408.

NextBio

1713.

SOURCE

Search...

Entry information

Entry name

ARRB1_HUMAN

Accession

Primary (citable) accession number: P49407
Secondary accession number(s): B6V9G8 , O75625, O75630, Q2PP20, Q9BTK8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	March 5, 2002
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.