Tbio ARRB1 Beta-arrestin-1

Protein Summary

Description

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. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates to the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940). Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]

Uniprot Accession IDs

• P49407
• B6V9G8
• O75625
• O75630
• Q2PP20
• Q9BTK8

Gene Name

• ARRB1

Ensembl ID

• ENST00000360025
• ENSP00000353124
• ENSG00000137486
• ENST00000420843
• ENSP00000409581

Symbol

• ARR1
• ARB1
• ARR1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
molecular function	1
disease perturbation	0.96
interacting protein	0.95

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Beta-arrestin-1

DTO Classes

Protein / Enzyme Modulator / Beta-arrestin-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 398.46   (req: < 5)

Gene RIFs: 144   (req: <= 3)

Antibodies: 648   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 398.46   (req: >= 5)

Gene RIFs: 144   (req: > 3)

Antibodies: 648   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 56

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

Related Tools (3)

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

Go To Tool

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

Go To Tool

ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

Go To Tool

Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (781)

Explore Interacting Targets

1 – 10 of 781

• See Interactions on String-DB

ARRB2

Tbio

Novelty:  0.00148149

p_int:  1

Score:  0.968

Data Source:  BioPlex,STRINGDB

SAG

Tbio

Novelty:  0.00040944

p_int:  0.999999994

p_wrong:  6e-9

Score:  0.427

Data Source:  BioPlex,STRINGDB

BRPF1

Tchem

Family:  Epigenetic

Novelty:  0.02524021

p_int:  0.99999922

p_ni:  7.76e-7

p_wrong:  4e-9

Score:  0.82

Data Source:  BioPlex,STRINGDB

RTF1

Tbio

Family:  Enzyme

Novelty:  0.02255644

p_int:  0.999715915

p_ni:  0.000267235

p_wrong:  0.00001685

Score:  0.821

Data Source:  BioPlex,STRINGDB

NOLC1

Tbio

Novelty:  0.01922261

p_int:  0.999652607

p_ni:  0.000347393

Score:  0.602

Data Source:  BioPlex,STRINGDB

DOCK4

Tbio

Novelty:  0.02356655

p_int:  0.999618081

p_ni:  0.000381918

Score:  0.189

Data Source:  BioPlex,STRINGDB

ALDH4A1

Tbio

Family:  Enzyme

Novelty:  0.01316227

p_int:  0.997706757

p_ni:  0.001123693

p_wrong:  0.00116955

Score:  0.331

Data Source:  BioPlex,STRINGDB

LYRM7

Tbio

Novelty:  0.16270565

p_int:  0.993036822

p_ni:  0.006884987

p_wrong:  0.000078191

Data Source:  BioPlex

ACIN1

Tbio

Novelty:  0.01675479

p_int:  0.941516508

p_ni:  0.058483492

Data Source:  BioPlex

HDGFL2

Tbio

Family:  Epigenetic

Novelty:  0.11846257

p_int:  0.937476039

p_ni:  0.055005481

p_wrong:  0.00751848

Score:  0.237

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (5)

Explore Nearest Tclin Targets

Upstream (1)

Downstream (4)

1 – 1 of 1

IL1R1

Tclin

Family:  Other

KEGG Distance:  4

Common Pathways:  1

1: MAPK signaling pathway

Pathways (65)

Reactome (41)

KEGG (9)

PathwayCommons (9)

WikiPathways (6)

Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 41

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activated NOTCH1 Transmits Signal to the Nucleus	31 targets	R-HSA-2122948
Reactome	Activation of SMO	18 targets	R-HSA-5635838
Reactome	Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Reactome	Clathrin-mediated endocytosis	143 targets	R-HSA-8856828
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215

Name	Explore in Pharos	Explore in Source
Activated NOTCH1 Transmits Signal to the Nucleus	31 targets	R-HSA-2122948
Activation of SMO	18 targets	R-HSA-5635838
Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Clathrin-mediated endocytosis	143 targets	R-HSA-8856828
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (74)

Functions (19)

Components (18)

Processes (37)

Find Similar Targets

Items per page:

10

1 – 10 of 19

GO Term	Evidence	Assigned by
angiotensin receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
arrestin family protein binding	Inferred from Physical Interaction (IPI)	UniProtKB
insulin-like growth factor receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
GTPase activator activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
transcription regulatory region DNA binding	Inferred from Mutant Phenotype (IMP)	BHF-UCL
enzyme inhibitor activity	Traceable Author Statement (TAS)	ProtInc
alpha-1A adrenergic receptor binding	Inferred from Electronic Annotation (IEA)	Ensembl
alpha-1B adrenergic receptor binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations (null)

No disease associations found

GWAS Traits (0)

No GWAS traits found

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Cell membrane
Cell projection
Coated pit
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Membrane
Nucleus

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
hematopoietic system phenotype
muscle phenotype
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	arrestin beta 1	VGNC:11261	451424
Macaque	arrestin beta 1		695250
Mouse	arrestin, beta 1	MGI:99473	109689
Rat	arrestin, beta 1	RGD:2156	25387
Dog	arrestin beta 1	VGNC:38136	485189

Species	Name	OMA	EggNOG	Inparanoid
Chimp	arrestin beta 1
Macaque	arrestin beta 1
Mouse	arrestin, beta 1
Rat	arrestin, beta 1
Dog	arrestin beta 1

Publication Statistics

PubMed Score 398.46

PubMed score by year

Reset Zoom

PubTator Score 563.43

PubTator score by year

Reset Zoom

Related Publications

Text Mined References (210)

GeneRif Annotations (144)

Items per page:

10

0 of 0

PMID	Year	Title