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FLASH GENE
Symbol ARRB1 contributors: mct - updated : 18-12-2015
HGNC name arrestin, beta 1
HGNC id 711
Location 11q13.4      Physical location : 74.976.481 - 75.062.873
Synonym name arrestin 2
Synonym symbol(s) ARR1, ARB1
DNA
TYPE functioning gene
STRUCTURE 86.39 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 - 2204 47.1 418 - 2005 16181421
15 splicing 2180 46.1 410 - 2005 16181421
lacking an alternate in-frame exon compared to variant 1
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
cells
SystemCellPubmedSpeciesStageRna symbol
Visualrod photoreceptor
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N- terminus of ARRB1 (AAs 1186) is critical for binding to TP53
  • arrestin C terminal domain
  • mono polymer heteromer , trimer
    HOMOLOGY
    interspecies homolog to murine Sag
    intraspecies homolog to alpha transducin,to ARRB2
    homolog to arrb2
    Homologene
    FAMILY
  • arrestin family
  • CATEGORY regulatory , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,chromatin/chromosome
    text
  • nuclear translocation induced by the stimulation of delta-opioid receptor, a member of the GPCR family
  • cytosolic ARRB1 mediates catecholamine-induced activation of AKT and MDM2, whereas nuclear ARRB1 serves as an adaptor for MDM2-dependent ubiquitination of TP53
  • mediates signaling within the nucleus
  • basic FUNCTION
  • agonist induced phosphorylation dependent G protein coupled receptors internalisation and desentisation
  • Ca2+ binding protein of the retinal rod outer segments, binding to P-rhodopsin
  • inhibiting further G protein activation desensitized receptor-arrestin complex and sequestered through clathrin coated pits
  • also regulator of beta-adrenergic receptor A and activator of the lymphoid enhancer factor (LEF) transcription factor
  • involved in synaptic transmission in photoreceptor cells
  • playing a crucial role for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase
  • facilitating the recruitment of histone acetyltransferase p300 by selective enrichment at specific promoters such as that of p27 and c-fos
  • having a broad role in the trafficking of integral plasma membrane protein
  • beta-arrestin-mediated signaling regulates protein synthesis
  • required for the maintenance of a ADRB1-EGFR interaction that can direct cytosolic targeting of ERK in response to catecholamine stimulation
  • both ARRB1 and ARRB2 play a novel and shared role in inhibiting G protein-dependent ERK1/2 phosphorylation
  • emerging role of ARRB1 as an E3-ligase adaptor in the nucleus
  • critical role for ARRB1 nuclear localization in scaffolding and transcriptional regulation
  • ARRB1, ARRB2 are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling
  • role in promoting thrombus formation, in part through its participation in ITGA2/ITGB3 signalling
  • ARRB1, ARRB2 are now widely accepted as endocytic and signaling adaptors for G protein-coupled receptors (GPCRs), growth factor receptors, and ion channels
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling neurotransmission , signal transduction
    a component
  • AGAP2 formed a complex with ARRB1 and ARRB2, proteins that are known to regulate beta2-adrenergic receptor signalling and trafficking
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DVLZ, DVL1 (enhanced by phosphorylation)
  • required with G protein (alphaq/11) for full activation of RhoA and subsequent formation of stress fibers
  • novel functions of ARRB1 in binding to the GNB1/GNG2 subunits of heterotrimeric G-proteins and promoting GNB-mediated Akt signalling GNB1/GNG2 for NF-kappaB activation
  • binding to MAP2K1, influencing the phosphorylation and the internalization of ARRB1
  • interacts with ESCRT-0, a protein complex that recognizes and sorts ubiquitinated cargo into the degradative pathway
  • NEDD4 and ARRB1 as key regulators of SLC9A1 ubiquitylation, endocytosis, and function
  • SHH inducing ARRB1 accumulation and localization to the nucleus, where it participates in enhancing expression of CDKN1B, whose accumulation eventually drives granule neuron precursors (CGNPs) cell cycle exit
  • plays a central role in coupling MIF endocytosis to sustained ERK activation
  • represses adipogenesis and inflammatory responses through its interaction with peroxisome proliferator-activated receptor-gamma (PPARG)
  • upon catecholamine stimulation, ARRB1 promotes the interaction of MDM2 and TP53 by acting as an E3 ligase adaptor that facilitates ubiquitination of p53
  • role for nuclear-localized ARRB1 in the regulation of NFKB activation
  • ARRB1 is a nuclear transcriptional regulator of EDN1-induced CTNNB1 signaling
  • dispensable for STAT1 dephosphorylation and the termination of IFNG signaling
  • engagement of ACKR2 by its ligands activates a ARRB1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the RAC1-PAK1-LIMK1 cascade
  • ARRB1 plays a critical role in the assembly and activation of two major canonical inflammasomes, NLRC4, NLRP3
  • ARRB1, ARRB2 bind constitutively to the most common DRD4 polymorphic variants and to KLHL12 and all three proteins can interact within a single macromolecular complex
  • ARRB1 and STAM cooperate to promote focal adhesion kinase autophosphorylation and chemotaxis via the chemokine receptor CXCR4
  • cell & other
    REGULATION
    activated by AVPR2, that functionally and conformationally activate ARRB1
    Other phosphorylation by GRK5 that regulates G protein-independent signalling
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS