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FLASH GENE
Symbol RGS4 contributors: mct - updated : 18-01-2023
HGNC name regulator of G-protein signaling 4
HGNC id 10000
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one RGS domain
  • amphipatic helix
  • HOMOLOGY
    interspecies homolog to murine Rgs4
    intraspecies homolog to RGS1
    Homologene
    FAMILY
  • regulator of G protein family
  • regulator of G protein subfamily R4
  • CATEGORY tumor suppressor , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • localizes to plasma membrane (PM) and endosomal compartments 3)
  • basic FUNCTION
  • negatively regulating signaling upstream or at the level of the heterotrimeric G protein
  • regulates G proteins that gate potassium channels and Ca2+ channel
  • has GTPase-activating protein (GAP) activity, which inhibits G-protein coupled receptor signaling by deactivating G-proteins
  • suppressor of breast cancer migration and invasion, important steps of metastatic cascades
  • plays a key role in G protein coupling selectivity and signaling of the OPRMs and OPRDs
  • play an important role in regulating beta-cell function
  • acts as a GTPase accelerating protein to modulate OPRM1 and OPRD1 signaling
  • opioid agonist-induced reduction in RGS4 occurs via the ubiquitin-proteasome pathway and may contribute to the maintenance of cell homeostasis in the morphine-dependent state
  • is a multitask protein that interacts with and negatively modulates opioid receptor signalling
  • both RGS2 and RGS4 play positive roles during adipogenesis but opposing roles during osteogenesis, with RGS2 is a positive regulator and RGS4 is a negative regulator
  • RGS4 promoted cardiac fibrosis and attenuated the anti-cardiac fibrosis of choline
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text inhibiting chondrocyte differentiation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with the C-termini of mu- and delta-opioid receptors
  • LMX1A is an activator of RGS4 and GRB10 and is responsible for the correct specification of rostral and medial mesodiencephalic dopamine (mdDA) neurons
  • both RAB5A activation and RAB11A inhibition decreased RGS4 function in a manner that is independent from their effects on the localization and function of the M1R/Gq signaling complex
  • RGS2 and RGS4 are new interacting partners that play key roles in G protein coupling to negatively regulate OPRK1 signaling
  • RGS4 in the paraventricular nucleus (PVN) regulates likely blood corticosteroid-related GABBR1 signaling during the acute stress response
  • crucial role of ATE1 in neural tube development is directly related to proper turn-over of the RGS4 protein, which participate in the oxygen-sensing mechanism in the cells
  • RGS4 is implicated in opioid dependent neuronal differentiation and neurite outgrowth via a "non-canonical" signaling pathway regulating STAT5B-directed responses
  • RGS4 controls secretion of von Willebrand factor (VWF) to the subendothelial matrix
  • SPARC promoted glucose-stimulated insulin secretion (GSIS) by inhibiting RGS4 in pancreatic beta cells
  • RGS4 appears essential for propionate/FFAR3 signaling attenuation in both cardiomyocytes and sympathetic neurons, leading to cardioprotection against inflammation/adverse remodeling and to sympatholysis, respectively
  • cell & other
    REGULATION
    activated by co-expression of DHHC acyltransferases (DHHC3 or DHHC7), but not their acyltransferase-inactive mutants, increased expression levels of RGS4
    repressed by opioid agonists that reduce levels of RGS4 protein by an action to promote degradation
    ASSOCIATED DISORDERS
    corresponding disease(s) SCZD9
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in neuroblastoma cells (Wang 2009)
    Susceptibility to schizophrenia (SCZD9)
    Variant & Polymorphism SNP
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    may represent a potential target to promote insulin release for therapeutic purposes in type 2 diabetes
    neurosensorialear 
    intratympanic administration of RGS4 inhibitor CCG-4986 can rescue cochlear injury and hearing loss induced by acoustic overexposure
    ANIMAL & CELL MODELS