Search Results
Overview
| Uniprot ID | Q13227 |
|---|---|
| Protein Name | G protein pathway suppressor 2 |
| Gene Name | GPS2 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 151 | LMAADRAKQMFGPQV |
| 9 | PALLERPKLSNAMAR |
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 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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0005667 | transcription regulator complex |
| Cellular Component | GO:0017053 | transcription repressor complex |
| Molecular Function | GO:0030332 | cyclin binding |
| Molecular Function | GO:0005095 | GTPase inhibitor activity |
| Molecular Function | GO:0003713 | transcription coactivator activity |
| Molecular Function | GO:0003712 | transcription coregulator activity |
| Molecular Function | GO:0003714 | transcription corepressor activity |
| Biological Process | GO:0030183 | B cell differentiation |
| Biological Process | GO:0006351 | DNA-templated transcription |
| Biological Process | GO:0007254 | JNK cascade |
| Biological Process | GO:0050859 | negative regulation of B cell receptor signaling pathway |
| Biological Process | GO:0045599 | negative regulation of fat cell differentiation |
| Biological Process | GO:0050728 | negative regulation of inflammatory response |
| Biological Process | GO:0046329 | negative regulation of JNK cascade |
| Biological Process | GO:1900045 | negative regulation of protein K63-linked ubiquitination |
| Biological Process | GO:0034122 | negative regulation of toll-like receptor signaling pathway |
| Biological Process | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| Biological Process | GO:0010804 | negative regulation of tumor necrosis factor-mediated signaling pathway |
| Biological Process | GO:0010875 | positive regulation of cholesterol efflux |
| Biological Process | GO:0035360 | positive regulation of peroxisome proliferator activated receptor signaling pathway |
| Biological Process | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| Biological Process | GO:0045598 | regulation of fat cell differentiation |
| Biological Process | GO:0019216 | regulation of lipid metabolic process |
| Biological Process | GO:0006357 | regulation of transcription by RNA polymerase II |
| Biological Process | GO:0098780 | response to mitochondrial depolarisation |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[3] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.