ARRB2
entrez
409
canonical
uniprot
P32121
canonical
ensembl
ENSG00000141480
resolver
ensp
ENSP00000269260
resolver
ensp
ENSP00000341895
resolver
ensp
ENSP00000370898
resolver
ensp
ENSP00000403701
resolver
ensp
ENSP00000460607
resolver
ensp
ENSP00000465296
resolver
ensp
ENSP00000466344
resolver
ensp
ENSP00000466857
resolver
ensp
ENSP00000525496
resolver
enst
ENST00000571206
resolver
enst
ENST00000572457
resolver
enst
ENST00000574954
resolver
enst
ENST00000575877
resolver
genesymbol
ARRB2
resolver
genesymbol
DKFZp686L0365
resolver
genesymbol_syn
ARB2
resolver
genesymbol_syn
ARR2
resolver
hgnc
HGNC:712
resolver
uniprot
B4DLW0
resolver
uniprot
B5B0C0
resolver
uniprot
B7WPL3
resolver
uniprot
D3DTK2
resolver
uniprot
E7EMN1
resolver
uniprot
H0Y688
resolver
uniprot
K7EJS0
resolver
uniprot
K7ENA6
resolver
uniprot
Q0Z8D3
resolver
uniprot
Q2PP19
resolver
uniprot
Q59EM5
resolver
uniprot
Q68DZ5
resolver
uniprot
Q6ICT3
resolver
uniprot
Q8N7Y2
resolver
uniprot
Q9UEQ6
resolver
uniprot_entry
ARRB2_HUMAN
resolver
uniprot_entry
K7EJS0_HUMAN
resolver
uniprot_entry
K7ENA6_HUMAN
resolver
uniprot_entry
Q59EM5_HUMAN
resolver
uniprot_entry
Q68DZ5_HUMAN
resolver
uniprot_sec
B4DLW0
resolver
uniprot_sec
B5B0C0
resolver
uniprot_sec
B7WPL3
resolver
uniprot_sec
D3DTK2
resolver
uniprot_sec
E7EMN1
resolver
uniprot_sec
H0Y688
resolver
uniprot_sec
Q0Z8D3
resolver
uniprot_sec
Q2PP19
resolver
uniprot_sec
Q6ICT3
resolver
uniprot_sec
Q8N7Y2
resolver
uniprot_sec
Q9UEQ6
resolver
amino_acid_sequence
MGEKPGTRVFKKSSPNCKLTVYLGKRDFVDHLDKVDPVDGVVLVDPDYLKDRKVFVTLTCAFRYGREDLDVLGLSFRKDLFIATYQAFPPVPNPPRPPTRLQDRLLRKLGQHAHPFFFTIPQNLPCSVTLQPGPEDTGKACGVDFEIRAFCAKSLEEKSHKRNSVRLVIRKVQFAPEKPGPQPSAETTRHFLMSDRSLHLEASLDKELYYHGEPLNVNVHVTNNSTKTVKKIKVSVRQYADICLFSTAQYKCPVAQLEQDDQVSPSSTFCKVYTITPLLSDNREKRGLALDGKLKHEDTNLASSTIVKEGANKEVLGILVSYRVKVKLVVSRGGDVSVELPFVLMHPKPHDHIPLPRPQSAAPETDVPVDTNLIEFDTNYATDDDIVFEDFARLRLKGMKDDDYDDQLC
uniprot
proteins
function
FUNCTION: Functions in regulating agonist-mediated G protein-coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes (PubMed:16179383, PubMed:37209686, PubMed:38175886, PubMed:40384633). 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 (PubMed:16179383, PubMed:37209686, PubMed:38175886, PubMed:40384633). 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 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 (PubMed:15618519). 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 (PubMed:26839314). 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 IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:22282525, PubMed:23809162). During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation (PubMed:23809162). {ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:11877451, ECO:0000269|PubMed:12488444, ECO:0000269|PubMed:12582207, ECO:0000269|PubMed:12949261, ECO:0000269|PubMed:12958365, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15054093, ECO:0000269|PubMed:15125834, ECO:0000269|PubMed:15205453, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15618519, ECO:0000269|PubMed:15635042, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15699339, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16179383, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:18604210, ECO:0000269|PubMed:19325136, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:22282525, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23809162, ECO:0000269|PubMed:24817116, ECO:0000269|PubMed:26839314, ECO:0000269|PubMed:37209686, ECO:0000269|PubMed:38175886, ECO:0000269|PubMed:40384633}.
uniprot
proteins
mass_dalton
46106
uniprot
proteins
mutagenesis
MUTAGEN 11; /note="K->A: Abolishes interaction with CHUK; when associated with A-12; A-230 and A-231."; MUTAGEN 12; /note="K->A: Abolishes interaction with CHUK; when associated with A-11; A-230 and A-231."; MUTAGEN 54; /note="V->A: Inhibits internalization of CXCR4; no effect on interaction with CXCR4."; /evidence="ECO:0000269|PubMed:10644702"; MUTAGEN 230; /note="K->A: Abolishes interaction with CHUK; when associated with A-11; A-12 and A-231."; MUTAGEN 231; /note="K->A: Abolishes interaction with CHUK; when associated with A-11; A-12 and A-230."; MUTAGEN 360; /note="S->A,D: Reduces interaction with CHUK; when associated with A-382."; MUTAGEN 382; /note="T->A,D: Reduces interaction with CHUK; when associated with A-360."; /evidence="ECO:0000269|PubMed:11877451"; MUTAGEN 382; /note="T->A: Loss of phosphorylation."; /evidence="ECO:0000269|PubMed:11877451
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Thr-382 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1. {ECO:0000269|PubMed:11877451}.; 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 (PubMed:26839314). {ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:26839314}.; 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:0000269|PubMed:21255264}.
uniprot
proteins
protein_family
Arrestin family
uniprot
proteins
pubmed
10644702
uniprot
proteins
pubmed
10748214
uniprot
proteins
pubmed
10973280
uniprot
proteins
pubmed
11279203
uniprot
proteins
pubmed
11877451
uniprot
proteins
pubmed
12488444
uniprot
proteins
pubmed
12582207
uniprot
proteins
pubmed
12949261
uniprot
proteins
pubmed
12958365
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14711824
uniprot
proteins
pubmed
15054093
uniprot
proteins
pubmed
15125834
uniprot
proteins
pubmed
15205453
uniprot
proteins
pubmed
15475570
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15618519
uniprot
proteins
pubmed
15635042
uniprot
proteins
pubmed
15671180
uniprot
proteins
pubmed
15699339
uniprot
proteins
pubmed
1587386
uniprot
proteins
pubmed
15878855
uniprot
proteins
pubmed
15888437
uniprot
proteins
pubmed
16144840
uniprot
proteins
pubmed
16179383
uniprot
proteins
pubmed
16280323
uniprot
proteins
pubmed
16319069
uniprot
proteins
pubmed
16378096
uniprot
proteins
pubmed
16492667
uniprot
proteins
pubmed
16516836
uniprot
proteins
pubmed
16524428
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16820410
uniprot
proteins
pubmed
17540773
uniprot
proteins
pubmed
18419762
uniprot
proteins
pubmed
18604210
uniprot
proteins
pubmed
19325136
uniprot
proteins
pubmed
19363159
uniprot
proteins
pubmed
19416857
uniprot
proteins
pubmed
19620252
uniprot
proteins
pubmed
19643177
uniprot
proteins
pubmed
19782076
uniprot
proteins
pubmed
20048153
uniprot
proteins
pubmed
21255264
uniprot
proteins
pubmed
22282525
uniprot
proteins
pubmed
22300987
uniprot
proteins
pubmed
22457824
uniprot
proteins
pubmed
23341447
uniprot
proteins
pubmed
23809162
uniprot
proteins
pubmed
23886940
uniprot
proteins
pubmed
24817116
uniprot
proteins
pubmed
26839314
uniprot
proteins
pubmed
28827538
uniprot
proteins
pubmed
35427647
uniprot
proteins
pubmed
37209686
uniprot
proteins
pubmed
37660910
uniprot
proteins
pubmed
38175886
uniprot
proteins
pubmed
40384633
uniprot
proteins
pubmed
9346876
uniprot
proteins
sequence_length
409
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane. Membrane, clathrin-coated pit {ECO:0000250}. Cytoplasmic vesicle. Note=Translocates to the plasma membrane and colocalizes with antagonist-stimulated GPCRs.
uniprot
proteins