ARRB2 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0006366Biological processtranscription by RNA polymerase II
GO_0016567Biological processprotein ubiquitination
GO_0007628Biological processadult walking behavior
GO_0031623Biological processreceptor internalization
GO_0032226Biological processpositive regulation of synaptic transmission, dopaminergic
GO_0002029Biological processdesensitization of G protein-coupled receptor signaling pathway
GO_0032715Biological processnegative regulation of interleukin-6 production
GO_0060079Biological processexcitatory postsynaptic potential
GO_2000727Biological processpositive regulation of cardiac muscle cell differentiation
GO_0010628Biological processpositive regulation of gene expression
GO_0032695Biological processnegative regulation of interleukin-12 production
GO_0001934Biological processpositive regulation of protein phosphorylation
GO_0032691Biological processnegative regulation of interleukin-1 beta production
GO_0002092Biological processpositive regulation of receptor internalization
GO_0032088Biological processnegative regulation of NF-kappaB transcription factor activity
GO_0051898Biological processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_0001933Biological processnegative regulation of protein phosphorylation
GO_0045953Biological processnegative regulation of natural killer cell mediated cytotoxicity
GO_0031397Biological processnegative regulation of protein ubiquitination
GO_0034122Biological processnegative regulation of toll-like receptor signaling pathway
GO_0098926Biological processpostsynaptic signal transduction
GO_0002031Biological processG protein-coupled receptor internalization
GO_0051897Biological processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_0015031Biological processprotein transport
GO_0032720Biological processnegative regulation of tumor necrosis factor production
GO_0070374Biological processpositive regulation of ERK1 and ERK2 cascade
GO_0007212Biological processG protein-coupled dopamine receptor signaling pathway
GO_0007179Biological processtransforming growth factor beta receptor signaling pathway
GO_0043124Biological processnegative regulation of canonical NF-kappaB signal transduction
GO_0060326Biological processcell chemotaxis
GO_0043161Biological processproteasome-mediated ubiquitin-dependent protein catabolic process
GO_0098978Cellular componentglutamatergic synapse
GO_0005886Cellular componentplasma membrane
GO_0031410Cellular componentcytoplasmic vesicle
GO_0030139Cellular componentendocytic vesicle
GO_0005654Cellular componentnucleoplasm
GO_0098794Cellular componentpostsynapse
GO_0005829Cellular componentcytosol
GO_0005737Cellular componentcytoplasm
GO_0005905Cellular componentclathrin-coated pit
GO_0005634Cellular componentnucleus
GO_0019899Molecular functionenzyme binding
GO_0031748Molecular functionD1 dopamine receptor binding
GO_0060090Molecular functionmolecular adaptor activity
GO_0005102Molecular functionsignaling receptor binding
GO_0031625Molecular functionubiquitin protein ligase binding
GO_0001664Molecular functionG protein-coupled receptor binding
GO_0031701Molecular functionangiotensin receptor binding
GO_0043422Molecular functionprotein kinase B binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameARRB2
Protein nameAlternative protein ARRB2
Beta-arrestin-2 (Arrestin beta-2)
Beta-arrestin-2 (Arrestin beta-2) (Non-visual arrestin-3)
Arrestin beta 2
SynonymsARR2
ARB2
DKFZp686L0365
DescriptionFUNCTION: 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. 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 endocytosis of smoothened homolog/Smo, which also requires GRK2. 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 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 . During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation . .

AccessionsENST00000412477.7 [P32121-4]
I3L0V6
ENST00000576235.1
K7EL17
L8ECB1
ENST00000572457.5
ENST00000381488.10 [P32121-5]
Q68DZ5
ENST00000572497.5
ENST00000574954.5
P32121
I3L1M6
ENST00000346341.6 [P32121-2]
ENST00000571206.1
ENST00000269260.7 [P32121-1]
ENST00000574502.5
I3L412
K7ENA6
ENST00000571428.5
ENST00000575877.5