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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Assigned HPA protein class(es) for the encoded protein(s).
Transporters
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
17
Cytoband
p13.2
Chromosome location (bp)
4710596 - 4721499
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
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 1. 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 2,3. During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation 4....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Signal transduction inhibitor
Biological process (UniProt)i
Keywords assigned by UniProt to proteins because they are involved in a particular biological process.
Protein transport, Transport
Gene summary (Entrez)i
Useful information about the gene from Entrez
Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Transporters Accessory Factors Involved in Transport Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0001664[G protein-coupled receptor binding] GO:0001932[regulation of protein phosphorylation] GO:0001933[negative regulation of protein phosphorylation] GO:0001934[positive regulation of protein phosphorylation] GO:0002031[G protein-coupled receptor internalization] GO:0002032[desensitization of G protein-coupled receptor signaling pathway by arrestin] GO:0002092[positive regulation of receptor internalization] GO:0005102[signaling receptor binding] GO:0005515[protein binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005737[cytoplasm] GO:0005768[endosome] GO:0005829[cytosol] GO:0005886[plasma membrane] GO:0005905[clathrin-coated pit] GO:0006366[transcription by RNA polymerase II] GO:0006897[endocytosis] GO:0007165[signal transduction] GO:0007179[transforming growth factor beta receptor signaling pathway] GO:0007186[G protein-coupled receptor signaling pathway] GO:0007212[dopamine receptor signaling pathway] GO:0007420[brain development] GO:0007628[adult walking behavior] GO:0008277[regulation of G protein-coupled receptor signaling pathway] GO:0009968[negative regulation of signal transduction] GO:0010628[positive regulation of gene expression] GO:0014069[postsynaptic density] GO:0015031[protein transport] GO:0016020[membrane] GO:0016323[basolateral plasma membrane] GO:0016567[protein ubiquitination] GO:0019899[enzyme binding] GO:0019904[protein domain specific binding] GO:0030139[endocytic vesicle] GO:0031397[negative regulation of protein ubiquitination] GO:0031410[cytoplasmic vesicle] GO:0031623[receptor internalization] GO:0031625[ubiquitin protein ligase binding] GO:0031691[alpha-1A adrenergic receptor binding] GO:0031692[alpha-1B adrenergic receptor binding] GO:0031701[angiotensin receptor binding] GO:0031702[type 1 angiotensin receptor binding] GO:0031748[D1 dopamine receptor binding] GO:0031762[follicle-stimulating hormone receptor binding] GO:0031826[type 2A serotonin receptor binding] GO:0031859[platelet activating factor receptor binding] GO:0032088[negative regulation of NF-kappaB transcription factor activity] GO:0032226[positive regulation of synaptic transmission, dopaminergic] GO:0032691[negative regulation of interleukin-1 beta production] GO:0032695[negative regulation of interleukin-12 production] GO:0032715[negative regulation of interleukin-6 production] GO:0032720[negative regulation of tumor necrosis factor production] GO:0032967[positive regulation of collagen biosynthetic process] GO:0033138[positive regulation of peptidyl-serine phosphorylation] GO:0034122[negative regulation of toll-like receptor signaling pathway] GO:0034260[negative regulation of GTPase activity] GO:0034392[negative regulation of smooth muscle cell apoptotic process] GO:0042699[follicle-stimulating hormone signaling pathway] GO:0042802[identical protein binding] GO:0043154[negative regulation of cysteine-type endopeptidase activity involved in apoptotic process] GO:0043161[proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0043197[dendritic spine] GO:0043422[protein kinase B binding] GO:0043524[negative regulation of neuron apoptotic process] GO:0044877[protein-containing complex binding] GO:0045211[postsynaptic membrane] GO:0045953[negative regulation of natural killer cell mediated cytotoxicity] GO:0050731[positive regulation of peptidyl-tyrosine phosphorylation] GO:0050804[modulation of chemical synaptic transmission] GO:0050965[detection of temperature stimulus involved in sensory perception of pain] GO:0051019[mitogen-activated protein kinase binding] GO:0051897[positive regulation of protein kinase B signaling] GO:0051898[negative regulation of protein kinase B signaling] GO:0051928[positive regulation of calcium ion transport] GO:0060079[excitatory postsynaptic potential] GO:0060326[cell chemotaxis] GO:0070374[positive regulation of ERK1 and ERK2 cascade] GO:0071889[14-3-3 protein binding] GO:0090201[negative regulation of release of cytochrome c from mitochondria] GO:0098926[postsynaptic signal transduction] GO:0098978[glutamatergic synapse] GO:1904037[positive regulation of epithelial cell apoptotic process] GO:1990763[arrestin family protein binding] GO:2000573[positive regulation of DNA biosynthetic process] GO:2000727[positive regulation of cardiac muscle cell differentiation]
Transporters Accessory Factors Involved in Transport Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0001664[G protein-coupled receptor binding] GO:0002031[G protein-coupled receptor internalization] GO:0002032[desensitization of G protein-coupled receptor signaling pathway by arrestin] GO:0002092[positive regulation of receptor internalization] GO:0005102[signaling receptor binding] GO:0005515[protein binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0005886[plasma membrane] GO:0005905[clathrin-coated pit] GO:0006366[transcription by RNA polymerase II] GO:0007165[signal transduction] GO:0007179[transforming growth factor beta receptor signaling pathway] GO:0007212[dopamine receptor signaling pathway] GO:0009968[negative regulation of signal transduction] GO:0015031[protein transport] GO:0016020[membrane] GO:0016567[protein ubiquitination] GO:0019899[enzyme binding] GO:0030139[endocytic vesicle] GO:0031397[negative regulation of protein ubiquitination] GO:0031410[cytoplasmic vesicle] GO:0031623[receptor internalization] GO:0031625[ubiquitin protein ligase binding] GO:0031701[angiotensin receptor binding] GO:0032088[negative regulation of NF-kappaB transcription factor activity] GO:0043161[proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0045953[negative regulation of natural killer cell mediated cytotoxicity] GO:0051898[negative regulation of protein kinase B signaling] GO:0060079[excitatory postsynaptic potential] GO:0060326[cell chemotaxis] GO:0070374[positive regulation of ERK1 and ERK2 cascade]
Transporters Accessory Factors Involved in Transport Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0001664[G protein-coupled receptor binding] GO:0002031[G protein-coupled receptor internalization] GO:0002032[desensitization of G protein-coupled receptor signaling pathway by arrestin] GO:0002092[positive regulation of receptor internalization] GO:0005102[signaling receptor binding] GO:0005515[protein binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0005886[plasma membrane] GO:0005905[clathrin-coated pit] GO:0006366[transcription by RNA polymerase II] GO:0007165[signal transduction] GO:0007179[transforming growth factor beta receptor signaling pathway] GO:0007212[dopamine receptor signaling pathway] GO:0009968[negative regulation of signal transduction] GO:0015031[protein transport] GO:0016020[membrane] GO:0016567[protein ubiquitination] GO:0019899[enzyme binding] GO:0030139[endocytic vesicle] GO:0031397[negative regulation of protein ubiquitination] GO:0031410[cytoplasmic vesicle] GO:0031623[receptor internalization] GO:0031625[ubiquitin protein ligase binding] GO:0031701[angiotensin receptor binding] GO:0032088[negative regulation of NF-kappaB transcription factor activity] GO:0043161[proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0045953[negative regulation of natural killer cell mediated cytotoxicity] GO:0051898[negative regulation of protein kinase B signaling] GO:0060079[excitatory postsynaptic potential] GO:0060326[cell chemotaxis] GO:0070374[positive regulation of ERK1 and ERK2 cascade]
Transporters Accessory Factors Involved in Transport SCAMPI predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0001664[G protein-coupled receptor binding] GO:0002031[G protein-coupled receptor internalization] GO:0002032[desensitization of G protein-coupled receptor signaling pathway by arrestin] GO:0002092[positive regulation of receptor internalization] GO:0005102[signaling receptor binding] GO:0005515[protein binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0005886[plasma membrane] GO:0005905[clathrin-coated pit] GO:0006366[transcription by RNA polymerase II] GO:0007165[signal transduction] GO:0007179[transforming growth factor beta receptor signaling pathway] GO:0007212[dopamine receptor signaling pathway] GO:0009968[negative regulation of signal transduction] GO:0015031[protein transport] GO:0016020[membrane] GO:0016567[protein ubiquitination] GO:0019899[enzyme binding] GO:0030139[endocytic vesicle] GO:0031397[negative regulation of protein ubiquitination] GO:0031410[cytoplasmic vesicle] GO:0031623[receptor internalization] GO:0031625[ubiquitin protein ligase binding] GO:0031701[angiotensin receptor binding] GO:0032088[negative regulation of NF-kappaB transcription factor activity] GO:0043161[proteasome-mediated ubiquitin-dependent protein catabolic process] GO:0045953[negative regulation of natural killer cell mediated cytotoxicity] GO:0051898[negative regulation of protein kinase B signaling] GO:0060079[excitatory postsynaptic potential] GO:0060326[cell chemotaxis] GO:0070374[positive regulation of ERK1 and ERK2 cascade]
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)