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Protein

Beta-arrestin-1

Gene

ARRB1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Involved in IL8-mediated granule release in neutrophils. Binds phosphoinositides. Binds inositol hexakisphosphate (InsP6) (By similarity). 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 (By similarity).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei250Inositol hexakisphosphate1
Binding sitei255Inositol hexakisphosphate1
Binding sitei324Inositol hexakisphosphate1
Binding sitei326Inositol hexakisphosphate1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Protein transport, Transcription, Transcription regulation, Transport

Enzyme and pathway databases

ReactomeiR-BTA-418555. G alpha (s) signalling events.
R-BTA-432720. Lysosome Vesicle Biogenesis.
R-BTA-432722. Golgi Associated Vesicle Biogenesis.
R-BTA-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-BTA-5635838. Activation of SMO.
R-BTA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-BTA-8856828. Clathrin-mediated endocytosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-arrestin-1
Alternative name(s):
Arrestin beta-1
Arrestin-2
Gene namesi
Name:ARRB1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 15

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: Ensembl
  • clathrin-coated pit Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: UniProtKB
  • cytosol Source: Ensembl
  • nucleoplasm Source: Ensembl
  • plasma membrane Source: UniProtKB
  • pseudopodium Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi157K → Q: Impairs InsP6-binding and oligomerization; when associated with Q-160 and Q-161. 1 Publication1
Mutagenesisi160K → Q: Impairs InsP6-binding and oligomerization; when associated with Q-157 and Q-161. 1 Publication1
Mutagenesisi161R → Q: Impairs InsP6-binding and oligomerization; when associated with Q-157 and Q-160. 1 Publication1
Mutagenesisi232K → Q: Impairs InsP6-binding and oligomerization; when associated with Q-236, Q-250, Q-324 and Q-326. 1 Publication1
Mutagenesisi236R → Q: Impairs InsP6-binding and oligomerization; when associated with Q-232, Q-250, Q-324 and Q-326. 1 Publication1
Mutagenesisi250K → Q: Impairs InsP6-binding and oligomerization; when associated with Q-232, Q-236, Q-324 and Q-326. 1 Publication1
Mutagenesisi324K → Q: Impairs InsP6-binding and oligomerization; when associated with Q-232, Q-236, Q-250 and Q-326. 1 Publication1
Mutagenesisi326K → Q: Impairs InsP6-binding and oligomerization; when associated with Q-232, Q-236, Q-250 and Q-324. 1 Publication1
Mutagenesisi391F → A: Abolishes interaction with AP2B1; no effect on interaction with CLTC. 1 Publication1
Mutagenesisi395R → E: Abolishes interaction with AP2B1; impairs interaction with CLTC. 1 Publication1
Mutagenesisi396L → A: Impairs interaction with AP2B1; no effect on interaction with CLTC. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002051931 – 418Beta-arrestin-1Add BLAST418

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47PhosphotyrosineBy similarity1
Modified residuei412Phosphoserine; by GRK5By similarity1

Post-translational modificationi

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.
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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP17870.
PeptideAtlasiP17870.
PRIDEiP17870.

Expressioni

Tissue specificityi

Beta-arrestin 1A is found in cortex, cerebellum, striatum, pineal gland, retina and heart. Beta-arrestin 1B is found in spleen, lung, pituitary and kidney.

Gene expression databases

BgeeiENSBTAG00000020485.
ExpressionAtlasiP17870. baseline and differential.

Interactioni

Subunit structurei

Monomer. Homodimer. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB2; the association is mediated by InsP6-binding. 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 GRK2. 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). Interacts with GPR143 (By similarity). Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated) (By similarity). Interacts ACKR3 and ACKR4 (By similarity).By similarity

Protein-protein interaction databases

DIPiDIP-61028N.
STRINGi9913.ENSBTAP00000027296.

Structurei

Secondary structure

1418
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 12Combined sources7
Beta strandi14 – 17Combined sources4
Beta strandi19 – 23Combined sources5
Beta strandi25 – 29Combined sources5
Beta strandi31 – 34Combined sources4
Beta strandi37 – 42Combined sources6
Helixi45 – 48Combined sources4
Beta strandi52 – 64Combined sources13
Turni71 – 73Combined sources3
Beta strandi75 – 88Combined sources14
Beta strandi91 – 93Combined sources3
Helixi99 – 107Combined sources9
Beta strandi112 – 117Combined sources6
Beta strandi121 – 123Combined sources3
Beta strandi127 – 130Combined sources4
Helixi133 – 138Combined sources6
Beta strandi140 – 153Combined sources14
Helixi160 – 162Combined sources3
Beta strandi163 – 172Combined sources10
Beta strandi185 – 189Combined sources5
Beta strandi191 – 195Combined sources5
Beta strandi197 – 204Combined sources8
Beta strandi206 – 209Combined sources4
Beta strandi214 – 222Combined sources9
Beta strandi224 – 226Combined sources3
Beta strandi228 – 241Combined sources14
Beta strandi243 – 245Combined sources3
Beta strandi247 – 258Combined sources12
Beta strandi266 – 274Combined sources9
Helixi278 – 280Combined sources3
Turni281 – 283Combined sources3
Beta strandi285 – 291Combined sources7
Beta strandi293 – 295Combined sources3
Helixi313 – 315Combined sources3
Beta strandi316 – 329Combined sources14
Beta strandi333 – 335Combined sources3
Helixi336 – 338Combined sources3
Beta strandi342 – 352Combined sources11
Beta strandi355 – 358Combined sources4
Beta strandi386 – 390Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G4MX-ray1.90A/B1-393[»]
1G4RX-ray2.20A1-393[»]
1JSYX-ray2.90A1-418[»]
1ZSHX-ray2.90A1-418[»]
2WTRX-ray2.90A/B1-418[»]
3GC3X-ray2.20A1-393[»]
3GD1X-ray3.50C/E1-393[»]
DisProtiDP00390.
ProteinModelPortaliP17870.
SMRiP17870.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17870.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 163Interaction with SRCBy similarityAdd BLAST163
Regioni45 – 86Interaction with CHRM2Add BLAST42
Regioni318 – 418Interaction with TRAF6By similarityAdd BLAST101

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi385 – 395[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motifAdd BLAST11

Domaini

The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1. Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface (By similarity).By similarity
The N-terminus binds InsP6 with low affinity.
The C-terminus binds InsP6 with high affinity.

Sequence similaritiesi

Belongs to the arrestin family.Curated

Phylogenomic databases

eggNOGiKOG3865. Eukaryota.
ENOG410XR0F. LUCA.
GeneTreeiENSGT00390000013152.
HOGENOMiHOG000231319.
HOVERGENiHBG002399.
InParanoidiP17870.
KOiK04439.
OMAiLMHPKPL.
OrthoDBiEOG091G05M2.
TreeFamiTF314260.

Family and domain databases

Gene3Di2.60.40.640. 1 hit.
2.60.40.840. 1 hit.
InterProiIPR000698. Arrestin.
IPR011021. Arrestin-like_N.
IPR014752. Arrestin_C.
IPR011022. Arrestin_C-like.
IPR017864. Arrestin_CS.
IPR014753. Arrestin_N.
IPR014756. Ig_E-set.
[Graphical view]
PANTHERiPTHR11792. PTHR11792. 1 hit.
PfamiPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
PRINTSiPR00309. ARRESTIN.
SMARTiSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 2 hits.
PROSITEiPS00295. ARRESTINS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1A (identifier: P17870-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVEPVDGV VLVDPEYLKE
60 70 80 90 100
RRVYVTLTCA FRYGREDLDV LGLTFRKDLF VANVQSFPPA PEDKKPLTRL
110 120 130 140 150
QERLIKKLGE HAYPFTFEIP PNLPCSVTLQ PGPEDTGKAC GVDYEVKAFC
160 170 180 190 200
AENLEEKIHK RNSVRLVIRK VQYAPERPGP QPTAETTRQF LMSDKPLHLE
210 220 230 240 250
ASLDKEIYYH GEPISVNVHV TNNTNKTVKK IKISVRQYAD ICLFNTAQYK
260 270 280 290 300
CPVAMEEADD TVAPSSTFCK VYTLTPFLAN NREKRGLALD GKLKHEDTNL
310 320 330 340 350
ASSTLLREGA NREILGIIVS YKVKVKLVVS RGGLLGDLAS SDVAVELPFT
360 370 380 390 400
LMHPKPKEEP PHREVPEHET PVDTNLIELD TNDDDIVFED FARQRLKGMK
410
DDKEEEEDGT GSPRLNDR
Length:418
Mass (Da):47,132
Last modified:August 1, 1990 - v1
Checksum:i345302C620FA3360
GO
Isoform 1B (identifier: P17870-2) [UniParc]FASTAAdd to basket

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

Show »
Length:410
Mass (Da):46,375
Checksum:i61C47F9F7A7B0736
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000321334 – 341Missing in isoform 1B. Curated8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33601 mRNA. Translation: AAA30387.1.
PIRiA34851.
RefSeqiNP_776668.1. NM_174243.3. [P17870-1]
UniGeneiBt.52082.

Genome annotation databases

EnsembliENSBTAT00000027296; ENSBTAP00000027296; ENSBTAG00000020485. [P17870-1]
GeneIDi281637.
KEGGibta:281637.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33601 mRNA. Translation: AAA30387.1.
PIRiA34851.
RefSeqiNP_776668.1. NM_174243.3. [P17870-1]
UniGeneiBt.52082.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G4MX-ray1.90A/B1-393[»]
1G4RX-ray2.20A1-393[»]
1JSYX-ray2.90A1-418[»]
1ZSHX-ray2.90A1-418[»]
2WTRX-ray2.90A/B1-418[»]
3GC3X-ray2.20A1-393[»]
3GD1X-ray3.50C/E1-393[»]
DisProtiDP00390.
ProteinModelPortaliP17870.
SMRiP17870.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61028N.
STRINGi9913.ENSBTAP00000027296.

Proteomic databases

PaxDbiP17870.
PeptideAtlasiP17870.
PRIDEiP17870.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000027296; ENSBTAP00000027296; ENSBTAG00000020485. [P17870-1]
GeneIDi281637.
KEGGibta:281637.

Organism-specific databases

CTDi408.

Phylogenomic databases

eggNOGiKOG3865. Eukaryota.
ENOG410XR0F. LUCA.
GeneTreeiENSGT00390000013152.
HOGENOMiHOG000231319.
HOVERGENiHBG002399.
InParanoidiP17870.
KOiK04439.
OMAiLMHPKPL.
OrthoDBiEOG091G05M2.
TreeFamiTF314260.

Enzyme and pathway databases

ReactomeiR-BTA-418555. G alpha (s) signalling events.
R-BTA-432720. Lysosome Vesicle Biogenesis.
R-BTA-432722. Golgi Associated Vesicle Biogenesis.
R-BTA-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-BTA-5635838. Activation of SMO.
R-BTA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-BTA-8856828. Clathrin-mediated endocytosis.

Miscellaneous databases

EvolutionaryTraceiP17870.

Gene expression databases

BgeeiENSBTAG00000020485.
ExpressionAtlasiP17870. baseline and differential.

Family and domain databases

Gene3Di2.60.40.640. 1 hit.
2.60.40.840. 1 hit.
InterProiIPR000698. Arrestin.
IPR011021. Arrestin-like_N.
IPR014752. Arrestin_C.
IPR011022. Arrestin_C-like.
IPR017864. Arrestin_CS.
IPR014753. Arrestin_N.
IPR014756. Ig_E-set.
[Graphical view]
PANTHERiPTHR11792. PTHR11792. 1 hit.
PfamiPF02752. Arrestin_C. 1 hit.
PF00339. Arrestin_N. 1 hit.
[Graphical view]
PRINTSiPR00309. ARRESTIN.
SMARTiSM01017. Arrestin_C. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 2 hits.
PROSITEiPS00295. ARRESTINS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARRB1_BOVIN
AccessioniPrimary (citable) accession number: P17870
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 30, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.