Protein: G protein pathway suppressor 2 (GPS-2) (Q13227)
Organism: Homo sapiens (Human)
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. 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. 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. Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13. Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG. 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. 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. Acts as a tumor-suppressor in liposarcoma.
Subcellular location: Nucleus {ECO:0000269|PubMed:19858209, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:29499132}. Mitochondrion {ECO:0000269|PubMed:29499132}. Cytoplasm, cytosol {ECO:0000269|PubMed:24223774, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:29499132}. Note=Sumoylation regulates the subcellular location (PubMed:24943844). Relocates from the mitochondria to the nucleus following desumoylation, leading to mediate mitochondrial stress response (By similarity). {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:24943844}.
Interaction partners:
- F-box-like/WD repeat-containing protein TBL1Y
- F-box-like/WD repeat-containing protein TBL1X
- F-box-like/WD repeat-containing protein TBL1XR1
- Nuclear receptor corepressor 1
- Histone deacetylase 3
- Nuclear receptor corepressor 2
- COP9 signalosome complex subunit 1
- Histone acetyltransferase p300
- Transcriptional adapter 3
- ATP-binding cassette sub-family G member 1
Sequence:
MPALLERPKLSNAMARALHRHIMMERERKRQEEEEVDKMMEQKMKEEQERRKKKEMEERMSLEETKEQILKLEEKLLALQEEKHQLFLQLKKVLHEEEKRRRKEQSDLTTLTSAAYQQSLTVHTGTHLLSMQGSPGGHNRPGTLMAADRAKQMFGPQVLTTRHYVGSAAAFAGTPEHGQFQGSPGGAYGTAQPPPHYGPTQPAYSPSQQLRAPSAFPAVQYLSQPQPQPYAVHGHFQPTQTGFLQPGGALSLQKQMEHANQQTGFSDSSSLRPMHPQALHPAPGLLASPQLPVQMQPAGKSGFAATSQPGPRLPFIQHSQNPRFYHK