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FLASH GENE
Symbol ARRB2 contributors: mct - updated : 18-03-2016
HGNC name arrestin, beta 2
HGNC id 712
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal receptor activation-recognition domain
  • a binding site for the common PDE4D catalytic unit
  • two regions in the beta-arrestin 2 C-domain that confer specificity for PDE4D5 binding
  • C-terminal secondary receptor-binding domain
  • HOMOLOGY
    intraspecies homolog to alpha transducin
    Homologene
    FAMILY
  • arrestin family
  • CATEGORY adaptor , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • predominant cytoplasmic distribution at steady state
  • ARRB2 and ARR3, localize to the centrosome, a key organelle involved in microtubule nucleation and bipolar mitotic spindle assembly
  • basic FUNCTION
  • Ca2+ binding protein of the retinal rd outer segments, binding to P-rhodopsin
  • inhibiting further G protein activation of desensitized receptor-arrestin complex and sequestering it through clathrin coated pits
  • also regulator of beta-adrenergic receptor A, enhancing beta2AR receptor mediated nuclear translocation of ERK
  • specialized adaptor/scaffolding protein required for internalization and signaling of members of the G protein-coupled receptor superfamily
  • having a broad role in the trafficking of integral plasma membrane protein
  • beta-arrestin-mediated signaling regulates protein synthesis
  • involved in synaptic transmission in photoreceptor cells
  • having a role as a positive regulator in NFKB signaling pathway by connecting CARD10 to GPCRs
  • key role in mediating cellular cytoprotective functions by a 7-transmembrane receptor and define the biochemical pathways involved
  • acts as a corepressor of androgen receptor (AR) by serving as a scaffold for MDM2 leading to the AR ubiquitylation and degradation
  • is required for complement C1QA expression in macrophages and constrains factor-independent survival
  • non-visual arrestins (ARR3, ARRB2) are novel centrosomal components and regulate normal centrosome function
  • both ARRB1 and ARRB2 play a novel and shared role in inhibiting G protein-dependent ERK1/2 phosphorylation
  • ARRB1, ARRB2 are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling
  • plays a critical role in BCR-ABL–induced CML through its downstream regulation of CTNNB1 signaling
  • regulates insulin sensitivity in both skeletal muscle and liver
  • unlikely to be involved in the regulation of insulin secretion, but it is required for beta cell mass plasticity
  • ARRB1, ARRB2 are now widely accepted as endocytic and signaling adaptors for G protein-coupled receptors (GPCRs), growth factor receptors, and ion channels
  • negatively regulates TLR4-mediated inflammatory reactions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of AIP4
  • arrestin-2 complex that functions on endosomes to regulate sorting of CXCR4 into the degradative pathway
  • its subcellular localization and function is tightly regulated by MDM2 E3 ligase activity
  • 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
  • endosomal sorting molecule together with AIP4 to mediate CXCR4 entry into a degradative pathway
  • interaction with SLC9A5 (sequences within the N-terminal receptor activation-recognition domain and the C-terminal secondary receptor-binding domain of ARRB2 conferred strong binding to the C terminus of SLC9A5)
  • associated with CARD10, a scaffold protein that plays an essential role in GPCR-induced NFKB activation, suggesting that it may recruit CARD10 to Lysophosphatidic acid receptors
  • binding between a distal C-terminus fragment of cannabinoid receptor 1 (CNR1) and arrestin-2 (ARRB2)
  • ARRB2-RAF1 interaction is enhanced by receptor binding
  • ARRB2 is a scaffolding protein that regulates TRPV1 receptor activity
  • TRPV1 association with ARRB2 is critical to receptor desensitization via its ability to scaffold the phosphodiesterase PDE4D5 to the receptor, regulating TRPV1 phosphorylation
  • ARRB2 mediates the internalization of FFAR2 by agonist
  • ARRB2 regulates cannabinoid CB1 receptors in brain
  • lactate negatively regulates TLR induction of the NLRP3 inflammasome and production of IL1B, via ARRB2 and HCAR1
  • ARRB2 associates with phosphorylated TIGIT for further recruitment of INPP5D (SH2-containing inositol phosphatase 1) through the ITT-like motif
  • RACK1 and ARRB2 attenuate dimerization of PDE4 cAMP phosphodiesterase PDE4D5
  • role for ARRB2 in the mediation of SSTR3 ciliary signaling
  • regulates the reciprocal functions of ARRB2 in TLR4-promoted Nuclear Factor kappaB (NFKB) activation
  • 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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    may contribute to impaired insulin secretion in type 2 diabetes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS