======= ARRB1 =======
== Gene Information ==
* **Official Symbol**: ARRB1
* **Official Name**: arrestin beta 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=408|408]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P49407|P49407]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=ARRB1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ARRB1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/107940|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: 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 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011].
* **UniProt Summary**: 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. 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 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 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. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates to the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940). {ECO:0000250, ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15611106, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:18337459, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:23886940}.
|Arrestin C|
|Arrestin N|
|V2 vasopressin receptor binding|
|alpha-1A adrenergic receptor binding|
|follicle-stimulating hormone receptor binding|
|angiotensin receptor binding|
|protein phosphorylated amino acid binding|
|alpha-1B adrenergic receptor binding|
|follicle-stimulating hormone signaling pathway|
|positive regulation of histone H4 acetylation|
|arrestin family protein binding|
|AP-2 adaptor complex binding|
|clathrin adaptor activity|
|mitogen-activated protein kinase kinase binding|
|G protein-coupled receptor internalization|
|regulation of histone H4 acetylation|
|positive regulation of smooth muscle cell apoptotic process|
|insulin-like growth factor receptor binding|
|pseudopodium|
|contractile actin filament bundle assembly|
|stress fiber assembly|
|negative regulation of interleukin-8 production|
|negative adaptation of signaling pathway|
|desensitization of G protein-coupled receptor signaling pathway|
|adaptation of signaling pathway|
|regulation of smooth muscle cell apoptotic process|
|positive regulation of receptor internalization|
|cysteine-type endopeptidase inhibitor activity involved in apoptotic process|
|positive regulation of muscle cell apoptotic process|
|positive regulation of Rho protein signal transduction|
|positive regulation of histone acetylation|
|enzyme inhibitor activity|
|positive regulation of insulin secretion involved in cellular response to glucose stimulus|
|positive regulation of peptidyl-lysine acetylation|
|positive regulation of protein acetylation|
|negative regulation of Notch signaling pathway|
|ovulation cycle process|
|estrogen receptor binding|
|negative regulation of interleukin-6 production|
|phototransduction|
|negative regulation of GTPase activity|
|negative regulation of G protein-coupled receptor signaling pathway|
|histone acetyltransferase activity|
|ovarian follicle development|
|positive regulation of receptor-mediated endocytosis|
|clathrin-coated pit|
|regulation of receptor internalization|
|regulation of histone acetylation|
|regulation of insulin secretion involved in cellular response to glucose stimulus|
|detection of light stimulus|
|receptor internalization|
|regulation of peptidyl-lysine acetylation|
|actin filament bundle assembly|
|positive regulation of Ras protein signal transduction|
|actin filament bundle organization|
|negative regulation of ERK1 and ERK2 cascade|
|G protein-coupled receptor binding|
|ovulation cycle|
|regulation of muscle cell apoptotic process|
|regulation of interleukin-8 production|
|positive regulation of small GTPase mediated signal transduction|
|regulation of protein acetylation|
|positive regulation of insulin secretion|
|negative regulation of protein ubiquitination|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|negative regulation of NF-kappaB transcription factor activity|
|negative regulation of protein modification by small protein conjugation or removal|
|female gonad development|
|positive regulation of histone modification|
|negative regulation of cysteine-type endopeptidase activity|
|development of primary female sexual characteristics|
|positive regulation of protein binding|
|positive regulation of peptide hormone secretion|
|regulation of receptor-mediated endocytosis|
|positive regulation of endocytosis|
|regulation of Notch signaling pathway|
|positive regulation of chromatin organization|
|positive regulation of peptidyl-serine phosphorylation|
|receptor metabolic process|
|female sex differentiation|
|histone acetylation|
|actomyosin structure organization|
|chromatin|
|positive regulation of protein ubiquitination|
|internal peptidyl-lysine acetylation|
|detection of external stimulus|
|peptidyl-lysine acetylation|
|detection of abiotic stimulus|
|internal protein amino acid acetylation|
|ion channel binding|
|positive regulation of hormone secretion|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of protein modification by small protein conjugation or removal|
|regulation of peptidyl-serine phosphorylation|
|platelet activation|
|regulation of interleukin-6 production|
|regulation of Rho protein signal transduction|
|cytoplasmic vesicle membrane|
|regulation of G protein-coupled receptor signaling pathway|
|protein acetylation|
|negative regulation of neuron apoptotic process|
|regulation of histone modification|
|dendritic spine|
|positive regulation of cysteine-type endopeptidase activity|
|activation of MAPK activity|
|negative regulation of DNA-binding transcription factor activity|
|negative regulation of MAPK cascade|
|positive regulation of endopeptidase activity|
|positive regulation of chromosome organization|
|positive regulation of binding|
|regulation of insulin secretion|
|protein acylation|
|regulation of chromatin organization|
|positive regulation of peptidase activity|
|basolateral plasma membrane|
|postsynaptic membrane|
|regulation of protein ubiquitination|
|regulation of endocytosis|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|gonad development|
|regulation of peptide hormone secretion|
|positive regulation of ERK1 and ERK2 cascade|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|development of primary sexual characteristics|
|transcription regulatory region DNA binding|
|regulation of protein binding|
|regulation of protein modification by small protein conjugation or removal|
|receptor-mediated endocytosis|
|actin filament organization|
|regulation of cysteine-type endopeptidase activity|
|regulation of Ras protein signal transduction|
|negative regulation of endopeptidase activity|
|cytoplasmic vesicle|
|postsynaptic density|
|negative regulation of peptidase activity|
|positive regulation of MAP kinase activity|
|sex differentiation|
|regulation of hormone secretion|
|endosome|
|positive regulation of protein secretion|
|negative regulation of cytokine production|
|rhythmic process|
|GTPase activator activity|
|nuclear body|
|positive regulation of peptide secretion|
|ubiquitin protein ligase binding|
|regulation of ERK1 and ERK2 cascade|
|blood coagulation|
|coagulation|
|hemostasis|
|lysosomal membrane|
|response to light stimulus|
|regulation of neuron death|
|peptidyl-lysine modification|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|activation of protein kinase activity|
|transcription factor binding|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of small GTPase mediated signal transduction|
|regulation of chromosome organization|
|proteasomal protein catabolic process|
|negative regulation of proteolysis|
|cellular process involved in reproduction in multicellular organism|
|positive regulation of proteolysis|
|histone modification|
|covalent chromatin modification|
|regulation of binding|
|positive regulation of secretion by cell|
|negative regulation of protein phosphorylation|
|positive regulation of GTPase activity|
|regulation of endopeptidase activity|
|positive regulation of protein transport|
|reproductive structure development|
|regulation of DNA-binding transcription factor activity|
|reproductive system development|
|positive regulation of secretion|
|response to radiation|
|negative regulation of phosphorylation|
|regulation of peptidase activity|
|negative regulation of hydrolase activity|
|supramolecular fiber organization|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|wound healing|
|transcription by RNA polymerase II|
|regulation of GTPase activity|
|actin cytoskeleton organization|
|regulation of peptide secretion|
|regulation of body fluid levels|
|negative regulation of intracellular signal transduction|
|regulation of protein serine/threonine kinase activity|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|positive regulation of protein kinase activity|
|regulation of hormone levels|
|positive regulation of MAPK cascade|
|modification-dependent macromolecule catabolic process|
|regulation of vesicle-mediated transport|
|endocytosis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|actin filament-based process|
|response to wounding|
|positive regulation of kinase activity|
|proteolysis involved in cellular protein catabolic process|
|negative regulation of protein modification process|
|cellular protein catabolic process|
|Golgi membrane|
|positive regulation of organelle organization|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|RNA biosynthetic process|
|positive regulation of transferase activity|
|developmental process involved in reproduction|
|import into cell|
|protein catabolic process|
|protein ubiquitination|
|detection of stimulus|
|regulation of cytokine production|
|positive regulation of cell death|
|chromatin organization|
|regulation of protein transport|
|regulation of proteolysis|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|positive regulation of hydrolase activity|
|protein modification by small protein conjugation|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|regulation of secretion|
|multicellular organismal reproductive process|
|multicellular organism reproduction|
|membrane organization|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|cellular macromolecule catabolic process|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|apoptotic process|
|regulation of transferase activity|
|protein modification by small protein conjugation or removal|
|positive regulation of transport|
|negative regulation of cell death|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|positive regulation of phosphorylation|
|organonitrogen compound catabolic process|
|chromosome organization|
|cell activation|
|cell death|
|nucleobase-containing compound biosynthetic process|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|proteolysis|
|regulation of hydrolase activity|
|regulation of organelle organization|
|organic cyclic compound biosynthetic process|
|G protein-coupled receptor signaling pathway|
|negative regulation of cell communication|
|negative regulation of signaling|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|protein transport|
|peptide transport|
|regulation of apoptotic process|
|positive regulation of transcription, DNA-templated|
|regulation of programmed cell death|
|amide transport|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|RNA metabolic process|
|regulation of cell death|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|nitrogen compound transport|
|regulation of protein modification process|
|regulation of transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
No hits were found.
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 9930
* **Expression level (log2 read counts)**: 4.27
{{:chemogenomics:nalm6 dist.png?nolink |}}