External Ids for GPS2 Gene
Previous GeneCards Identifiers for GPS2 Gene
This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]
GeneCards Summary for GPS2 Gene
GPS2 (G Protein Pathway Suppressor 2) is a Protein Coding gene. Diseases associated with GPS2 include Hepatitis C Virus and Liposarcoma. Among its related pathways are HTLV-I infection and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. Gene Ontology (GO) annotations related to this gene include transcription corepressor activity and GTPase inhibitor activity.
UniProtKB/Swiss-Prot for GPS2 Gene
Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting Lys-63-linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:24943844). Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone H3 Lys-9 (H3K9) demethylation (By similarity). Promotes cholesterol efflux by acting as a transcription coactivator (PubMed:19481530). Acts as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B-cell antigen receptors (BCRs) signaling pathways (By similarity). Acts as a key mediator of mitochondrial stress response: in response to mitochondrial depolarization, relocates from the mitochondria to the nucleus following desumoylation and specifically promotes expression of nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG (PubMed:19858209, PubMed:24943844). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins, thereby preventing N-Cor corepressor complex dissociation (PubMed:20159957). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways (By similarity). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the proinflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (By similarity). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (By similarity). Able to suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction (PubMed:8943324). Acts as a tumor-suppressor in liposarcoma (PubMed:27460081).
(Microbial infection) Required for efficient replication of hepatitis C virus (HCV) by promoting the interaction between VAPA and HCV virus protein NS5A.