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FLASH GENE
Symbol RGS3 contributors: mct/npt - updated : 22-03-2017
HGNC name regulator of G-protein signaling 3
HGNC id 9999
Location 9q32      Physical location : 116.207.010 - 116.360.017
Synonym symbol(s) PDZ-RGS3, C2PA, FLJ20370, FLJ31516, FLJ90496, RGP3
DNA
TYPE functioning gene
STRUCTURE 153.01 kb     26 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
8 - 2914 56 519 - 2002 12036301
  • also called variant 2, or RGS3L
  • functions as a molecular switch, redirecting Gi-coupled receptors via Gbetagamma-dimers and PI3K from Rac1 to RhoA activation
  • 16 splicing 3741 - 917 ubiquitous 2002 12036301
    also called variant 1 or PDZ-RGS3
    18 splicing 2564 - 602 - 2002 12036301
    also called variant 3
    5 splicing 1582 23 168 expressed in heart 2002 12036301
  • also called variant 4, truncated variant
  • found predominantly in the nucleus and partially in the plasma membrane
  • RGS3T, localized to the nucleus and inducing apoptosis
  • caused cell rounding and membrane blebbing
  • in addition to being a GTPase-activating protein, RGS3T has other distinct functions in the nucleus of the cell
  • 5 splicing 1773 35 311 - 2002 12036301
  • also called variant 5
  • lack the synapsin domain
  • 26 splicing 4643 125 1198 testis 2002 12036301
  • also called variant 6 or C2PA-RGS3
  • 23 exons, 80kb
  • cytoplasmic, plasma membrane
  • may be involved in the heat shock response in testis
  • 23 - 4279 - 1088 - 2002 12036301
    15 - 2735 - 591 - 2002 12036301
    11 - 2116 - 433 - 2002 12036301
    7 - 2811 - 519 - 2002 12036301
    12 - 2757 - 537 - 2002 12036301
    5 - 1459 - 168 - 2002 12036301
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivesalivary gland   highly
    Lymphoid/Immunespleen   highly
    Nervousnerve   highly
    Reproductivemale systemtestis   
    Respiratorylung    
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one N terminal PDZ domain and a lengthy (approximately 380 AAs) N-terminal domain of uncertain physiological function, restricted to the cytoplasm (Toro-Castillo 2007)
  • one C2 domain
  • a core domain uniformly distributed throughout both cytoplasm and nucleus
  • alpha helical basic phosphoprotein, with eight consensus phosphorylation sites and a C terminal RGS domain, that bound to the YWHAQ dimer in an as-yet-unrecognized manner interacting with less conserved regions on the outer surface of the 14-3-3 dimer outside its central channel
  • a synapsin domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to C.elegans EGL-10
    homolog to yeast SST2
    intraspecies homolog to RGS2
    Homologene
    FAMILY
  • regulator of G-protein signaling (RGS) family
  • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text translocates to the membrane to inhibit G(q/11) signaling (Dulin 2000)
    basic FUNCTION
  • functioning as GTPase-activating protein for G protein alpha I and Q subunits
  • potential physiological regulator of R-type Ca(2+) channels (CACNA1E) (Toro-Castillo 2007)
  • regulates the signaling mediated by G(q) and G(i) proteins by binding the corresponding Galpha subunits (Yau 2008)
  • role of RGS3 in regulation of TGF-beta signaling through its interaction with Smads and interfering with Smad heteromerization (Yau 2008)
  • essential role of RGS3 in maintaining the balance between self-renewal and differentiation of neural progenitor cells and provide genetic evidence linking RGS3 to ephrin-B reverse signaling
  • can enhance signals generated by the Wnt canonical pathway and plays a pivotal role in epithelial mesenchymal transition (EMT)
  • RGS3 isoforms are impicated in the regulation of Wnt signaling and EMT
  • nonredundant role for endogenous RGS3 in controlling T cell migration in vitro and in an in vivo model of inflammation
  • negative regulator of G protein-mediated signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds EFNB1 and EFNB2
  • binds the GNB1- GNG2 heterodimer
  • interacts with the novel partners SMAD2, SMAD3, and SMAD4-the transcription factors that are activated through a transforming growth factor-beta (TGF-beta) receptor signaling (Yau 2008)
  • interacting with C5AR1 (in apoptosis-initiated cells, the ligand-dependent C5AR1-mediated dual signal affects the fate of cells, either apoptosis execution or survival, through regulation of RGS3 gene expression and subsequent modulation of ERK signal) (Nishiura 2009)
  • RGS3 bridges ephrin-B reverse signaling and CXCL12 induced G protein signaling
  • cell & other
    REGULATION
    inhibited by 14-3-3 protein (inhibitory effect of the 14-3-3 protein on GAP activity of RGS3) (Rezabkova 2010)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    results in inhibition of Smad-mediated gene transcription (Yau 2008)
    constitutional     --over  
    cardiac overexpression of RGS3 inhibits maladaptive hypertrophy and fibrosis and improves cardiac function by blocking MEK-ERK1/2 signaling
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS