Protein: G protein pathway suppressor 2 (GPS-2) (Q921N8)
Organism: Mus musculus (Mouse)
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. 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. Promotes cholesterol efflux by acting as a transcription coactivator (By similarity). 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. 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. 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 (By similarity). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways. In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the pro-inflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity. In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT. Able to suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:18218630, ECO:0000269|PubMed:22424771, ECO:0000269|PubMed:22666460, ECO:0000269|PubMed:26070566, ECO:0000269|PubMed:29499132}. Mitochondrion {ECO:0000269|PubMed:29499132}. Cytoplasm, cytosol {ECO:0000269|PubMed:22424771}. Note=Sumoylation regulates the subcellular location (PubMed:29499132). Relocates from the mitochondria to the nucleus following desumoylation, leading to mediate mitochondrial stress response (PubMed:29499132). {ECO:0000250|UniProtKB:Q13227, ECO:0000269|PubMed:29499132}.
Interaction partners:
- F-box-like/WD repeat-containing protein TBL1XR1
- F-box-like/WD repeat-containing protein TBL1X
- Nuclear receptor corepressor 1
- Histone deacetylase 3
- Nuclear receptor corepressor 2
- Homeobox protein goosecoid
- WD repeat-containing protein 26
- Guanine nucleotide-binding protein G
Sequence:
MPALLERPKLSNAMARALHRHIMMERERKRQEEEEVDKMMEQKMKEEQERRKKKEMEERMSLEETKEQILKLQEKLSALQEEKHQLFLQLKKVLHEEEKRRRKEQSDLTTLTSAAYQQSLTVHTGTHLLSMQGSPGGHNRPGTLMAADRAKQMFGPQVLTTRHYVGSAAAFAGTPEHGQFQGSPGGAYGTAQPPPHYGPTQPAYSPSQQLRAPSAFPAVQYLSQPQPQPYAVHGHFQPTQTGFLQPGSTLSLQKQMEHANQQTSFSDSSSLRPMHPQALHPAPGLLASPQLPVQIQAAGKSGFATTSQPGPRLPFIQHSQNPRFYHK