Arrb1
entrez
25387
canonical
uniprot
P29066
canonical
ensembl
ENSRNOG00000030404
resolver
ensp
ENSRNOP00000046069
resolver
ensp
ENSRNOP00000095275
resolver
ensp
ENSRNOP00000102308
resolver
ensp
ENSRNOP00000110444
resolver
ensp
ENSRNOP00000112649
resolver
enst
ENSRNOT00000043554
resolver
enst
ENSRNOT00000125345
resolver
enst
ENSRNOT00000143451
resolver
enst
ENSRNOT00000153802
resolver
genesymbol
Arrb1
resolver
uniprot
A0A8L2QMJ8
resolver
uniprot
A0ABK0LMM4
resolver
uniprot
A0ABK0M4Z5
resolver
uniprot
A0ABK0M5L6
resolver
uniprot_entry
A0A8L2QMJ8_RAT
resolver
uniprot_entry
A0ABK0LMM4_RAT
resolver
uniprot_entry
A0ABK0M4Z5_RAT
resolver
uniprot_entry
A0ABK0M5L6_RAT
resolver
uniprot_entry
ARRB1_RAT
resolver
amino_acid_sequence
MGDKGTRVFKKASPNGKLTVYLGKRDFVDHIDLVDPVDGVVLVDPEYLKERRVYVTLTCAFRYGREDLDVLGLTFRKDLFVANVQSFPPAPEDKKPLTRLQERLIKKLGEHAYPFTFEIPPNLPCSVTLQPGPEDTGKACGVDYEVKAFCAENLEEKIHKRNSVRLVIRKVQYAPERPGPQPTAETTRQFLMSDKPLHLEASLDKEIYYHGEPISVNVHVTNNTNKTVKKIKISVRQYADICLFNTAQYKCPVAMEEADDTVAPSSTFCKVYTLTPFLANNREKRGLALDGKLKHEDTNLASSTLLREGANREILGIIVSYKVKVKLVVSRGGLLGDLASSDVAVELPFTLMHPKPKEEPPHREVPESETPVDTNLIELDTNDDDIVFEDFARQRLKGMKDDKDEEDDGTGSPHLNNR
uniprot
proteins
function
FUNCTION: Functions in regulating agonist-mediated G protein-coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes (PubMed:37209686, PubMed:38175886). During homologous desensitization, beta-arrestins bind to the GPCR-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 a 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 a 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 (By similarity). Involved in smoothened (SMO) localization to primary cilium (By similarity). Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-protein ligase to the receptor (By similarity). Involved in some MRGPRE-mediated signaling required to improve glucose tolerance: promotes phosphorylation of ALDOA downstream of MRGPRE activation, increasing glycolysis and leading to GLP-1 secretion (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P49407, ECO:0000269|PubMed:10212203, ECO:0000269|PubMed:10347185, ECO:0000269|PubMed:10725339, ECO:0000269|PubMed:10747877, ECO:0000269|PubMed:10995467, ECO:0000269|PubMed:11579203, ECO:0000269|PubMed:11742073, ECO:0000269|PubMed:11777902, ECO:0000269|PubMed:11901145, ECO:0000269|PubMed:12399592, ECO:0000269|PubMed:12519791, ECO:0000269|PubMed:12821670, ECO:0000269|PubMed:15173580, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:17594911, ECO:0000269|PubMed:18006496, ECO:0000269|PubMed:22810587, ECO:0000269|PubMed:37209686, ECO:0000269|PubMed:38175886, ECO:0000269|PubMed:8553074, ECO:0000269|PubMed:9388255, ECO:0000269|PubMed:9822622, ECO:0000269|PubMed:9924018}.
uniprot
proteins
mass_dalton
47020
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="V->D: Inhibits internalization of EDNRA, EDNRB and ADRB2. No effect on interaction with SRC; impairs ADRB2- and HTR1A-mediated ERK phosphorylation; impairs sequestration of ADRB2."; /evidence="ECO:0000269|PubMed:10747877, ECO:0000269|PubMed:8553074, ECO:0000269|PubMed:9924018"; MUTAGEN 91; /note="P->G: Impairs interaction with SRC; impairs ADRB2- and HTR1A-mediated ERK phosphorylation; no effect on sequestration of ADRB2; when associated with E-121."; /evidence="ECO:0000269|PubMed:9924018"; MUTAGEN 121; /note="P->E: Impairs interaction with SRC; impairs ADRB2- and HTR1A-mediated ERK phosphorylation; no effect on sequestration of ADRB2; when associated with G-91."; /evidence="ECO:0000269|PubMed:9924018"; MUTAGEN 412; /note="S->A: Abolishes phosphorylation and inhibits ADRB2 endocytosis; no effect on interaction with ADRB2."; /evidence="ECO:0000269|PubMed:9388255, ECO:0000269|PubMed:9822622, ECO:0000269|PubMed:9924018"; MUTAGEN 412; /note="S->D: Impairs interaction with SRC; impairs ADRB2-mediated ERK phosphorylation and IGFR1-mediated MAP kinase phosphorylation of GAB1; impairs sequestration of ADRB2 and IGFR1; abolishes interaction with clathrin; no effect on interaction with ADRB2 and IGFR1."; /evidence="ECO:0000269|PubMed:9388255, ECO:0000269|PubMed:9822622, ECO:0000269|PubMed:9924018
uniprot
proteins
post_translational_modification
PTM: Constitutively phosphorylated at Ser-412 in the cytoplasm. At the plasma membrane, is rapidly dephosphorylated, a process that is required for clathrin binding and beta-2 adrenergic receptor/ADRB2 endocytosis but not for ADRB2 binding and desensitization. Once internalized, is rephosphorylated. {ECO:0000269|PubMed:9388255}.; PTM: 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). {ECO:0000250}.
uniprot
proteins
protein_family
Arrestin family
uniprot
proteins
pubmed
10097102
uniprot
proteins
pubmed
10212203
uniprot
proteins
pubmed
10347185
uniprot
proteins
pubmed
10725339
uniprot
proteins
pubmed
10747877
uniprot
proteins
pubmed
10753943
uniprot
proteins
pubmed
10770944
uniprot
proteins
pubmed
10973280
uniprot
proteins
pubmed
10995467
uniprot
proteins
pubmed
11579203
uniprot
proteins
pubmed
11742073
uniprot
proteins
pubmed
11777902
uniprot
proteins
pubmed
11777907
uniprot
proteins
pubmed
11901145
uniprot
proteins
pubmed
12399592
uniprot
proteins
pubmed
12519791
uniprot
proteins
pubmed
12821670
uniprot
proteins
pubmed
1517224
uniprot
proteins
pubmed
15173580
uniprot
proteins
pubmed
15878855
uniprot
proteins
pubmed
16641100
uniprot
proteins
pubmed
17594911
uniprot
proteins
pubmed
18006496
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
22810587
uniprot
proteins
pubmed
23886940
uniprot
proteins
pubmed
37209686
uniprot
proteins
pubmed
38175886
uniprot
proteins
pubmed
8553074
uniprot
proteins
pubmed
9388255
uniprot
proteins
pubmed
9822622
uniprot
proteins
pubmed
9924018
uniprot
proteins
sequence_length
418
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit {ECO:0000305}. Cell projection, pseudopodium. 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). {ECO:0000250}.
uniprot
proteins