Beta-arrestin-1 (ARRB1)
The protein contains 418 amino acids for an estimated molecular weight of 47066 Da.
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 membra (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
Biological Process
Activation of MAPK activity
Follicle-stimulating hormone signaling pathway
G protein-coupled receptor internalization
G protein-coupled receptor signaling pathway
Histone acetylation
Membrane organization
Negative regulation of ERK1 and ERK2 cascade
Negative regulation of GTPase activity
Negative regulation of interleukin-6 production
Negative regulation of interleukin-8 production
Negative regulation of neuron apoptotic process
Negative regulation of NF-kappaB transcription factor activity
Negative regulation of Notch signaling pathway
Negative regulation of protein phosphorylation
Negative regulation of protein ubiquitination
Phototransduction
Platelet activation
Positive regulation of cell population proliferation
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of histone acetylation
Positive regulation of histone H4 acetylation
Positive regulation of insulin secretion involved in cellular response to glucose stimulus
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of protein binding
Positive regulation of protein phosphorylation
Positive regulation of protein ubiquitination
Positive regulation of receptor internalization
Positive regulation of Rho protein signal transduction
Positive regulation of smooth muscle cell apoptotic process
Positive regulation of transcription by RNA polymerase II
Post-Golgi vesicle-mediated transport
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein transport
Protein ubiquitination
Regulation of transcription by RNA polymerase II
Response to drug
Stress fiber assembly
Transcription by RNA polymerase II
Ubiquitin-dependent protein catabolic process
Cellular Component
Basolateral plasma membrane
Chromatin
Clathrin-coated pit
Cytoplasm
Cytoplasmic vesicle
Cytoplasmic vesicle membrane
Cytosol
Dendritic spine
Endosome
Golgi membrane
Lysosomal membrane
Nuclear body
Nucleoplasm
Nucleus
Plasma membrane
Postsynaptic density
Postsynaptic membrane
Pseudopodium
Molecular Function
Alpha-1A adrenergic receptor binding
Alpha-1B adrenergic receptor binding
Angiotensin receptor binding
AP-2 adaptor complex binding
Arrestin family protein binding
Clathrin adaptor activity
Cysteine-type endopeptidase inhibitor activity involved in apoptotic process
Enzyme inhibitor activity
Estrogen receptor binding
Follicle-stimulating hormone receptor binding
G protein-coupled receptor binding
GTPase activator activity
Insulin-like growth factor receptor binding
Ion channel binding
Mitogen-activated protein kinase kinase binding
Protein phosphorylated amino acid binding
Transcription coactivator activity
Transcription factor binding
Transcription regulatory region DNA binding
Ubiquitin protein ligase binding
V2 vasopressin receptor binding
The reference OMIM entry for this protein is 107940
Arrestin, beta, 1; arrb1
Beta-arrestin 1; arb1
CLONING
Homologous or agonist-specific desensitization is a widespread process that causes specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. It is defined by a loss of responsiveness of receptors that have been continuously or repeatedly stimulated, while the responses of other receptors remain intact. Homologous desensitization of beta-adrenergic receptors is thought to be mediated by a specific kinase, called beta-adrenergic receptor kinase (BARK, or ADRBK1; 109635). A cofactor is required for this kinase to inhibit receptor function. Lohse et al. (1990) cloned the cDNA for this cofactor and found that it encodes a 418-amino acid protein homologous to the retinal protein arrestin.GENE FUNCTION
Lohse et al. (1990) found that purified beta-arrestin inhibited the signaling function of BARK-phosphorylated beta-adrenergic receptors by more than 75%, but not that of rhodopsin (180380). Luttrell et al. (1999) showed that stimulation of beta-2 adrenergic receptors (see 109690) resulted in the assembly of a protein complex containing activated SRC (SRC; 190090) and the receptor. They demonstrated that SRC binds to beta-arrestin-1 at its amino terminus. Beta-arrestin-1 mutants, impaired either in SRC binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of beta-2 adrenergic receptor-mediated activation of the MAP kinases ERK1 (601795) and ERK2 (176948). Buchanan et al. (2006) found that prostaglandin E2 (PGE2) induced association of PGE2 receptor-4 (PTGER4; 601586), beta-arrestin-1, and Src in a signaling complex that transactivated EGF receptor (EGFR; 131550) and downstream AKT (see AKT1; 164730) signaling. The interaction of beta-arrestin-1 with Src was critical for regulation of human colorectal carcinoma cell migration in vitro, as well as for metastatic spread of disease from spleen to liver in nude mice. Seven-transmembrane receptor signaling is transduced by second messengers such as diacylglycerol (DAG) generated in response to the heterotrimeric guanine nucleotide-binding protein G(q) (600998) and is terminated by receptor desensitization and degradation of the second messengers. Nelson et al. (2007) showed that beta-arrestins coordinate both processes for the G(q)-coupled M1 muscarinic receptor (CHRM1; 118510). Beta-arrestins physically interact with diacylglycerol kinases (see 125855), enzymes that degrade DAG. Moreover, beta-arrestins are essential for conversion of DAG to phosphatidic acid after agonist stimulation, and this activity requires recruitment of the beta-arrestin-DGK complex to activated 7-transmembrane receptors. The dual function of beta-arrestins, limiting production of diacylglycerol (by receptor desensitization) while enhancing its rate of degradation, is analogous to their ability to recruit adenosine 3-prime,5-prime-monophosphate phosphodiesterases to G(s) (139320)-coupled beta-2-adrenergic receptors (ADRB2; 109690). Thus, Nelson et al. (2007) concluded that beta-arrestins can serve similar regulatory functions for disparate classes of 7-transmembrane receptors through structurally dissimilar enzymes that degrade chemically distinct second messengers. Kovacs et al. (2008) demonstrated that beta-arrestins mediate the activity-dependent interaction of Smoothened (SMO; 601500) and the kinesin motor protein KIF3A (604683). This multimeric complex localized to primary cilia and was d ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 107940 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).