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FLASH GENE
Symbol GPS2 contributors: mct - updated : 24-01-2015
HGNC name G protein pathway suppressor 2
HGNC id 4550
Location 17p13.1      Physical location : 7.215.977 - 7.218.658
Synonym symbol(s) AMF-1, MGC104294, MGC119287, MGC119288
DNA
TYPE functioning gene
STRUCTURE 2.68 kb     11 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
- - 3740 36 327 - 1996 8943324
  • sharing some exons with variant 1
  • - - 2360 36 327 - 1996 8943324
  • differing by 5'utr from variant 2
  • 11 - 1181 - 327 - 1996 8943324
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two SUMOylation sites (K45 and K71) are identified in the N-terminal coiled-coil domain of GPS2
  • conjugated sumoylated
    HOMOLOGY
    interspecies homolog to Arabibopsis fus6 (copII)
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • suppressor of G protein and mitogen activated protein kinase mediated pathways
  • involved in transcriptional pathways governing bile acid biosynthesis, that differentially regulates two major enzymes, CYP7A1 and CYP8B1, via its interaction with NR0B2, NR5A2, HNF4A, and FXR1
  • is an integral component of the NCOR2 complexes, important for ligand-dependent gene regulations by ESR1 and a suppressor for MCF-7 cell proliferation
  • is a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis
  • ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenesis
  • suppressor of G protein-activated mitogen-activated protein kinase signaling
  • may thus serve as a unique target to manipulate PPARG signaling in diseases
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component integral component of a deacetylase complex (GPS2-associated deacetylase complex might function in concert with hMSH4-hMSH5 during the process of homologous recombination)
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interfering with JNK activity
  • interacts with RFX4C to modulate transactivation of genes involved in brain morphogenesis, including CX3CL1
  • selective requirement of GPS2 for ABCG1 cholesterol transporter gene transcription and cholesterol efflux from macrophages
  • TBL1X interacts with both NCOR2 and GPS2
  • regulatory cascade containing PPARG and TWIST1 that controlled the expression of GPS2 and NCOR2 in human adipocytes
  • SUMOylation stabilizes GPS2 protein by promoting its interaction with TBL1X and reducing its ubiquitination
  • NCOR1 and NCOR2 directly bind to transcription factors and nucleate the formation of stable complexes that include HDAC3, transducin b-like protein 1/TBL1-related protein 1, and GPS2
  • dispensable for the intrinsic repression function of NCOR1, can mediate a novel corepressor repression pathway that allows NCOR1 to directly repress active PPARG-mediated transcription
  • cell & other
    REGULATION
    Other can be modified by the small ubiquitin-like modifier (SUMO) SUMO1 but not SUMO2 or -3
    posttranslational modification of GPS2 by SUMOylation may serve as a key factor that regulates the function of GPS2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    significantly reduced in obese adipose tissue, inversely correlated to inflammatory status
    tumoral fusion      
    fusion gene MLL4-GPS2 in undifferentiated spindle cell sarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in Gps2-deficient mouse embryonic fibroblast cells, loss of Gps2 markedly reduces the corepressor function of NCoR1 for PPARg, leading to constitutive activation of PPARg target genes and spontaneous adipogenesis of the cells