GPS2

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.

G protein pathway suppressor 2

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.

B cell differentiation Source: UniProtKB
Inactivation of MAPK activity Source: ProtInc
JNK cascade Source: ProtInc
Negative regulation of B cell receptor signaling pathway Source: UniProtKB
Negative regulation of fat cell differentiation Source: UniProtKB
Negative regulation of inflammatory response Source: UniProtKB
Negative regulation of JNK cascade Source: UniProtKB
Negative regulation of protein K63-linked ubiquitination Source: UniProtKB
Negative regulation of toll-like receptor signaling pathway Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Negative regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Positive regulation of cholesterol efflux Source: UniProtKB
Positive regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Regulation of fat cell differentiation Source: UniProtKB
Regulation of lipid metabolic process Source: UniProtKB
Response to mitochondrial depolarisation Source: UniProtKB

Mitochondrion; Cytosol; Nucleus. Sumoylation regulates the subcellular location (PubMed:24943844). Relocates from the mitochondria to the nucleus following desumoylation, leading to mediate mitochondrial stress response (By similarity).

Sumoylation regulates its subcellular location (PubMed:24943844). Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the cytoplasm and the nucleus (PubMed:24943844). Sumoylation at Lys-71 is required for interaction with TBL1X (By similarity). Sumoylated at Lys-45 and Lys-71 in mitochondrion (By similarity). Desumoylation by SENP1 leads to relocation from the mitochondria to the nucleus (By similarity).
Ubiquitinated at the C-terminus by SIAH2; leading to its degradation by the proteasome. Interaction with TBL1X and methylation at Arg-323 protect GPS2 against ubiquitination and degradation.
Methylated at Arg-312 and Arg-323 by PRMT6. Methylation at Arg-323 protects from degradation by the proteasome.