GPS2
UniProt ID: Q13227
Entrez ID: 2874
Protein name: G protein pathway suppressor 2 (GPS-2)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: 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 coactiva...
FUNCTION: 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 pro-inflammatory 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). {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:19858209, ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:27460081, ECO:0000269|PubMed:29499132, ECO:0000269|PubMed:8943324}.; FUNCTION: (Microbial infection) Required for efficient replication of hepatitis C virus (HCV) by promoting the interaction between VAPA and HCV virus protein NS5A. {ECO:0000269|PubMed:24223774}.
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GO - Biological processes (BP):
B cell differentiation [GO:0030183]; JNK cascade [GO:0007254]; negative regulation of B cell receptor signaling pathway [GO:0050859]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of inflammatory response [GO:0050728]; negative regulation of JNK cascade [GO:004632...
B cell differentiation [GO:0030183]; JNK cascade [GO:0007254]; negative regulation of B cell receptor signaling pathway [GO:0050859]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of inflammatory response [GO:0050728]; negative regulation of JNK cascade [GO:0046329]; negative regulation of protein K63-linked ubiquitination [GO:1900045]; negative regulation of toll-like receptor signaling pathway [GO:0034122]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of tumor necrosis factor-mediated signaling pathway [GO:0010804]; positive regulation of cholesterol efflux [GO:0010875]; positive regulation of peroxisome proliferator activated receptor signaling pathway [GO:0035360]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of fat cell differentiation [GO:0045598]; regulation of lipid metabolic process [GO:0019216]; regulation of transcription by RNA polymerase II [GO:0006357]; response to mitochondrial depolarisation [GO:0098780]
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GO - Molecular function (MF):
cyclin binding [GO:0030332]; GTPase inhibitor activity [GO:0005095]; transcription coactivator activity [GO:0003713]; transcription coregulator activity [GO:0003712]; transcription corepressor activity [GO:0003714]...
cyclin binding [GO:0030332]; GTPase inhibitor activity [GO:0005095]; transcription coactivator activity [GO:0003713]; transcription coregulator activity [GO:0003712]; transcription corepressor activity [GO:0003714]
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GO - Cellular component (CC):
cytosol [GO:0005829]; mitochondrion [GO:0005739]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; transcription regulator complex [GO:0005667]; transcription repressor complex [GO:0017053]...
cytosol [GO:0005829]; mitochondrion [GO:0005739]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; transcription regulator complex [GO:0005667]; transcription repressor complex [GO:0017053]
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GPS2
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*NOTE: the Kaplan plots were collected from OncoLnc