Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ARRB2 contributors: mct - updated : 18-03-2016
HGNC name arrestin, beta 2
HGNC id 712
DNA
TYPE functioning gene
STRUCTURE 11.01 kb     15 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
14 - 1936 46 409 - 1993 8486659
14 - 1891 - 394 - 1993 8486659
15 - 1999 - 430 - -
15 - 1972 - 421 - -
15 - 1805 - 330 - -
14 - 1927
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreas   highly Mus musculus
Nervousbrain     Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...) Mus musculus
Nervousneuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
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