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FLASH GENE
Symbol GPSM3 contributors: mct - updated : 23-01-2024
HGNC name G-protein signaling modulator 3 (AGS3-like, C. elegans)
HGNC id 13945
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region is a novel G protein-interacting domain that may have distinct regulatory effects within the G(i/o) subfamily, and thus, it could potentially play a role in differentiating signals between these related G proteins
  • three G-protein regulatory motifs downstream of an amino terminus domain with multiple prolines
  • two GoLoco motifs to exert GDP dissociation inhibitor activity over Galpha(i) subunits
    • HOMOLOGY
    interspecies homolog to murine Gpsm3
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • having GTPase activator activity
  • GPSM3 acts as a direct negative regulator of NLRP3 function
  • is a regulator of G protein-coupled receptor signaling, with expression restricted to leukocytes and lymphoid organs
  • potential role for GPSM3 in the development of inflammation in rheumatoid arthritis, most likely through a key regulatory role on leukocyte chemotaxis to the synovium
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GPSM3 also interacts directly with numerous members of the 14-3-3 protein family, and this interaction is dependent on GPSM3 phosphorylation
  • GPSM3 is a NLRP3-interacting protein and a negative regulator of IL1B production triggered by NLRP3-dependent inflammasome activators
  • binding of GPSM3 to RGS5 appears to be selective as no interactions were detected with other RGS proteins
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    resulted in mild but significant neutropenia and leukocytosis
    tumoral     --over  
    in low-grade glioma and negatively correlated to the GPSM3 DNA methylation
    Susceptibility to rheumatoid arthritis
    Variant & Polymorphism other
  • SNPs rs204989 and rs204991, each previously associated with protection from rheumatoid arthritis
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Gpsm3-deficient mice exhibit a profoundly blunted course of joint damage in an acute, collagen antibody-induced model of inflammatory arthritis