Arrb2
entrez
25388
canonical
uniprot
P29067
canonical
ensembl
ENSRNOG00000019308
resolver
ensp
ENSRNOP00000095625
resolver
ensp
ENSRNOP00000102697
resolver
ensp
ENSRNOP00000103308
resolver
enst
ENSRNOT00000108666
resolver
enst
ENSRNOT00000133479
resolver
genesymbol
Arrb2
resolver
uniprot
A0A8I6APG4
resolver
uniprot
A0ABK0L2A2
resolver
uniprot_entry
A0A8I6APG4_RAT
resolver
uniprot_entry
A0ABK0L2A2_RAT
resolver
uniprot_entry
ARRB2_RAT
resolver
amino_acid_sequence
MGEKPGTRVFKKSSPNCKLTVYLGKRDFVDHLDKVDPVDGVVLVDPDYLKDRKVFVTLTCAFRYGREDLDVLGLSFRKDLFIATYQAFPPMPNPPRPPTRLQDRLLKKLGQHAHPFFFTIPQNLPCSVTLQPGPEDTGKACGVDFEIRAFCAKSIEEKSHKRNSVRLIIRKVQFAPETPGPQPSAETTRHFLMSDRRSLHLEASLDKELYYHGEPLNVNVHVTNNSAKTVKKIRVSVRQYADICLFSTAQYKCPVAQLEQDDQVSPSSTFCKVYTITPLLSDNREKRGLALDGQLKHEDTNLASSTIVKEGANKEVLGILVSYRVKVKLVVSRGGDVSVELPFVLMHPKPHDHITLPRPQSAPREIDIPVDTNLIEFDTNYATDDDIVFEDFARLRLKGMKDDDCDDQFC
uniprot
proteins
function
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 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. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. 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) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as a signaling scaffold for the AKT1 pathway. 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). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. 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. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in IL8-mediated granule release in neutrophils (By similarity). Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in both localization to primary cilium and endocytosis of smoothened (SMO) in a GRK2-dependent process. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. 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 insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in the internalization of the atypical chemokine receptor ACKR3 (By similarity). Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation. {ECO:0000250, ECO:0000250|UniProtKB:P32121, ECO:0000269|PubMed:10097102, ECO:0000269|PubMed:10747877, ECO:0000269|PubMed:11090355, ECO:0000269|PubMed:11226259, ECO:0000269|PubMed:11777902, ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:18006496, ECO:0000269|PubMed:18408005, ECO:0000269|PubMed:19055777, ECO:0000269|PubMed:22810587}.
uniprot
proteins
mass_dalton
46340
uniprot
proteins
mutagenesis
MUTAGEN 11..12; /note="KK->RR: Transient ubiquitination; no stable endocytic complexes with AGTR1; impaired in scaffolding-activated ERK1/2."; /evidence="ECO:0000269|PubMed:15699045"; MUTAGEN 18; /note="K->R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-107, R-108, R-207 and R-296."; /evidence="ECO:0000269|PubMed:19055777"; MUTAGEN 54; /note="V->A: Inhibits internalization of EDNRA and EDNRB."; /evidence="ECO:0000269|PubMed:10747877"; MUTAGEN 107; /note="K->R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-108, R-207 and R-296."; /evidence="ECO:0000269|PubMed:19055777"; MUTAGEN 108; /note="K->R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-107, R-207 and R-296."; /evidence="ECO:0000269|PubMed:19055777"; MUTAGEN 198; /note="S->P: Greatly reduces interaction with MAPK10."; /evidence="ECO:0000269|PubMed:18408005"; MUTAGEN 207; /note="K->R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-107, R-108 and R-296."; /evidence="ECO:0000269|PubMed:19055777"; MUTAGEN 296; /note="K->R: Promotes agonist-stimulated down-regulation of CHRM2 and CHRM1; no effect on internalization of CHRM2; when associated with R-18, R-107, R-108 and R-207."; /evidence="ECO:0000269|PubMed:19055777"; MUTAGEN 361; /note="S->D: Almost abolishes phosphorylation; inhibits internalization of ADRB2; when associated with D-383."; /evidence="ECO:0000269|PubMed:12186555"; MUTAGEN 361; /note="S->D: Reduces interaction with CLTC."; /evidence="ECO:0000269|PubMed:12186555"; MUTAGEN 374..377; /note="LIEF->AAEA: Abolishes interaction with CLTC; reduces interaction with AP2B1."; /evidence="ECO:0000269|PubMed:10097102"; MUTAGEN 383; /note="T->D: Almost abolishes phosphorylation; inhibits internalization of ADRB2; when associated with D-361."; /evidence="ECO:0000269|PubMed:12186555"; MUTAGEN 383; /note="T->D: Reduces interaction with CLTC."; /evidence="ECO:0000269|PubMed:12186555"; MUTAGEN 394; /note="R->A: Abolishes interaction with AP2B1; no effect on interaction with clathrin."; MUTAGEN 396; /note="R->A: Abolishes interaction with AP2B1."; /evidence="ECO:0000269|PubMed:10770944"; MUTAGEN 398; /note="K->A: No effect on interaction with AP2B1."; /evidence="ECO:0000269|PubMed:10770944
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Thr-383 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1 (By similarity). {ECO:0000250}.; 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. Stimulation of a class B GPCR promotes a sustained ubiquitination. Deubiquitinated by USP20; allowing USP20 to deubiquitinate TRAF6 leading to inhibition of NF-kappa-B signaling (By similarity). {ECO:0000250|UniProtKB:P32121}.; PTM: Hydroxylation by PHD2 modulates the rate of internalization by slowing down recruitment to the plasma membrane and inhibiting subsequent co-internalization with class A receptors. {ECO:0000250}.
uniprot
proteins
protein_family
Arrestin family
uniprot
proteins
pubmed
10097102
uniprot
proteins
pubmed
10747877
uniprot
proteins
pubmed
10753943
uniprot
proteins
pubmed
10770944
uniprot
proteins
pubmed
10852825
uniprot
proteins
pubmed
11090355
uniprot
proteins
pubmed
11226259
uniprot
proteins
pubmed
11448957
uniprot
proteins
pubmed
11588219
uniprot
proteins
pubmed
11777902
uniprot
proteins
pubmed
11777907
uniprot
proteins
pubmed
12186555
uniprot
proteins
pubmed
12464600
uniprot
proteins
pubmed
12944399
uniprot
proteins
pubmed
14500724
uniprot
proteins
pubmed
1517224
uniprot
proteins
pubmed
15173580
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15618519
uniprot
proteins
pubmed
15699045
uniprot
proteins
pubmed
15738310
uniprot
proteins
pubmed
15878855
uniprot
proteins
pubmed
16051150
uniprot
proteins
pubmed
17666399
uniprot
proteins
pubmed
18006496
uniprot
proteins
pubmed
18408005
uniprot
proteins
pubmed
19055777
uniprot
proteins
pubmed
22810587
uniprot
proteins
pubmed
23886940
uniprot
proteins
pubmed
8308033
uniprot
proteins
pubmed
9767391
uniprot
proteins
pubmed
9822622
uniprot
proteins
sequence_length
410
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Cell membrane. Membrane, clathrin-coated pit. Cytoplasmic vesicle {ECO:0000250}. Note=Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs.
uniprot
proteins