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P49407 (ARRB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-arrestin-1
Alternative name(s):
Arrestin beta-1
Gene names
Name:ARRB1
Synonyms:ARR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. 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.30 Ref.33 Ref.38 Ref.39 Ref.40

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). Interacts with ACKR3 and ACKR4. 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.32 Ref.34 Ref.38 Ref.39

Subcellular location

Cytoplasm. Nucleus. Cell membrane. Membraneclathrin-coated pit Probable. Cell projectionpseudopodium 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.31

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.34

Sequence similarities

Belongs to the arrestin family.

Ontologies

Keywords
   Biological processProtein transport
Transcription
Transcription regulation
Transport
   Cellular componentCell membrane
Cell projection
Coated pit
Cytoplasm
Cytoplasmic vesicle
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   Molecular functionSignal transduction inhibitor
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor internalization

Inferred from mutant phenotype PubMed 10521508PubMed 12582207. Source: UniProtKB

Notch signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

apoptotic DNA fragmentation

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

follicle-stimulating hormone signaling pathway

Inferred from electronic annotation. Source: Ensembl

membrane organization

Traceable author statement. Source: Reactome

negative regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of GTPase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.24. Source: UniProtKB

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

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 phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein ubiquitination

Inferred from direct assay Ref.24. Source: UniProtKB

phototransduction

Inferred from electronic annotation. Source: Ensembl

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 GTPase activity

Inferred from mutant phenotype Ref.16. Source: GOC

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 histone acetylation

Inferred from mutant phenotype Ref.15. Source: BHF-UCL

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from mutant phenotype Ref.40. Source: UniProtKB

positive regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

positive regulation of receptor internalization

Inferred from mutant phenotype Ref.38. Source: UniProtKB

positive regulation of smooth muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

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

proteasome-mediated 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_componentGolgi membrane

Traceable author statement. Source: Reactome

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

chromatin

Inferred from direct assay Ref.15. Source: BHF-UCL

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 10823817Ref.16Ref.15. Source: UniProtKB

cytoplasmic vesicle

Inferred from direct assay Ref.16. Source: UniProtKB

cytoplasmic vesicle membrane

Traceable author statement. Source: Reactome

cytosol

Traceable author statement. Source: Reactome

dendritic spine

Inferred from electronic annotation. Source: Ensembl

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

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

postsynaptic membrane

Inferred from electronic annotation. Source: Ensembl

pseudopodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionGTPase activator activity

Inferred from mutant phenotype Ref.16. Source: UniProtKB

angiotensin receptor binding

Inferred from physical interaction Ref.16. Source: UniProtKB

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

enzyme inhibitor activity

Traceable author statement PubMed 2163110. Source: ProtInc

insulin-like growth factor receptor binding

Inferred from physical interaction Ref.13. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.24Ref.25Ref.34Ref.38Ref.39. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.15. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from mutant phenotype Ref.15. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from physical interaction Ref.13. Source: UniProtKB

Complete GO annotation...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 418418Beta-arrestin-1
PRO_0000205194

Regions

Region1 – 163163Interaction with SRC By similarity
Region45 – 8642Interaction with CHRM2 By similarity
Region318 – 418101Interaction with TRAF6
Motif385 – 39511[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif

Sites

Binding site2501Inositol hexakisphosphate By similarity
Binding site2551Inositol hexakisphosphate By similarity
Binding site3241Inositol hexakisphosphate By similarity
Binding site3261Inositol hexakisphosphate By similarity

Amino acid modifications

Modified residue471Phosphotyrosine By similarity
Modified residue4121Phosphoserine; by GRK5 Ref.31 Ref.35 Ref.37

Natural variations

Alternative sequence334 – 3418Missing in isoform 1B.
VSP_000322

Experimental info

Mutagenesis1691R → E: Constitutive active; enables phosphorylation-independent binding to GPCRs. Ref.8
Mutagenesis3881F → A: Abolishes interaction with AP2B1. Ref.20
Mutagenesis3901D → P: Abolishes interaction with AP2B1. Ref.20
Mutagenesis3931R → A: Abolishes interaction with AP2B1. Ref.20
Sequence conflict1461V → A in AAA35559. Ref.1
Sequence conflict1461V → A in AAA35558. Ref.1
Sequence conflict1651R → G in AAA35559. Ref.1
Sequence conflict1651R → G in AAA35558. Ref.1
Sequence conflict2291K → E in AAA35559. Ref.1
Sequence conflict2291K → E in AAA35558. Ref.1
Sequence conflict3291V → E in AAC33295. Ref.2
Sequence conflict3291V → E in AAC34123. Ref.2
Sequence conflict4001K → E in AAA35559. Ref.1
Sequence conflict4001K → E in AAA35558. Ref.1
Sequence conflict4141Q → R in AAA35559. Ref.1
Sequence conflict4141Q → R in AAA35558. Ref.1
Sequence conflict4171N → D in AAA35559. Ref.1
Sequence conflict4171N → D in AAA35558. Ref.1

Secondary structure

... 418
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1A [UniParc].

Last modified March 5, 2002. Version 2.
Checksum: 0A3C135092338D10

FASTA41847,066
        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 

« Hide

Isoform 1B [UniParc].

Checksum: 4FBA2B09E6C2D236
Show »

FASTA41046,309

References

« Hide '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. expand/collapse author list , 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]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"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.
[31]"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.
[32]"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.
[33]"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.
[34]"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.
[35]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[36]"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].
[37]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[38]"Ubiquitination of CXCR7 controls receptor trafficking."
Canals M., Scholten D.J., de Munnik S., Han M.K., Smit M.J., Leurs R.
PLoS ONE 7:E34192-E34192(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACKR3.
[39]"Beta-arrestin recruitment and G protein signaling by the atypical human chemokine decoy receptor CCX-CKR."
Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M., van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J., Vischer H.F.
J. Biol. Chem. 288:7169-7181(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACKR4.
[40]"Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6."
Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B., Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R., Locati M.
Sci. Signal. 6:RA30-RA30(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[41]"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.
CCDSCCDS31640.1. [P49407-2]
CCDS44684.1. [P49407-1]
PIRB46682.
RefSeqNP_004032.2. NM_004041.4. [P49407-1]
NP_064647.1. NM_020251.3. [P49407-2]
UniGeneHs.503284.
Hs.625320.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IV8X-ray2.80P/Q383-402[»]
ProteinModelPortalP49407.
SMRP49407. Positions 5-393.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106901. 243 interactions.
DIPDIP-29979N.
IntActP49407. 204 interactions.
MINTMINT-128176.
STRING9606.ENSP00000377141.

Chemistry

BindingDBP49407.
ChEMBLCHEMBL1795088.

PTM databases

PhosphoSiteP49407.

Polymorphism databases

DMDM20141238.

2D gel databases

OGPP49407.

Proteomic databases

MaxQBP49407.
PaxDbP49407.
PRIDEP49407.

Protocols and materials databases

DNASU408.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360025; ENSP00000353124; ENSG00000137486. [P49407-2]
ENST00000420843; ENSP00000409581; ENSG00000137486. [P49407-1]
GeneID408.
KEGGhsa:408.
UCSCuc001owe.2. human. [P49407-1]
uc001owf.2. human. [P49407-2]

Organism-specific databases

CTD408.
GeneCardsGC11M074976.
HGNCHGNC:711. ARRB1.
HPACAB003763.
MIM107940. gene.
neXtProtNX_P49407.
PharmGKBPA59.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG302111.
HOGENOMHOG000231319.
HOVERGENHBG002399.
InParanoidP49407.
KOK04439.
OMAEAPIDTN.
OrthoDBEOG79W954.
PhylomeDBP49407.
TreeFamTF314260.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_116125. Disease.
REACT_604. Hemostasis.
SignaLinkP49407.

Gene expression databases

ArrayExpressP49407.
BgeeP49407.
CleanExHS_ARRB1.
GenevestigatorP49407.

Family and domain databases

Gene3D2.60.40.640. 1 hit.
2.60.40.840. 1 hit.
InterProIPR000698. Arrestin.
IPR011021. Arrestin-like_N.
IPR014752. Arrestin_C.
IPR011022. Arrestin_C-like.
IPR017864. Arrestin_CS.
IPR014753. Arrestin_N.
IPR014756. Ig_E-set.
[Graphical view]
PANTHERPTHR11792. PTHR11792. 1 hit.
PfamPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
PRINTSPR00309. ARRESTIN.
SMARTSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMSSF81296. SSF81296. 2 hits.
PROSITEPS00295. ARRESTINS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP49407.
GeneWikiArrestin_beta_1.
GenomeRNAi408.
NextBio1713.
PROP49407.
SOURCESearch...

Entry information

Entry nameARRB1_HUMAN
AccessionPrimary (citable) accession number: P49407
Secondary accession number(s): B6V9G8 expand/collapse secondary AC list , O75625, O75630, Q2PP20, Q9BTK8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: March 5, 2002
Last modified: July 9, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM