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 (PubMed:22424771, PubMed:24953653, PubMed:28039360, PubMed:28123943, PubMed:29499132). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:18218630, PubMed:24953653, PubMed:25519902, PubMed:27270589, PubMed:28039360). 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 (PubMed:22666460, PubMed:24953653). 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 (PubMed:28039360). 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:25519902). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (PubMed:27270589). 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 (PubMed:22424771, PubMed:28123943). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the proinflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (PubMed:22424771). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (PubMed:28123943). Able to suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction (By similarity).

327 amino acids

MPALLERPKLSNAMARALHRHIMMERERKRQEEEEVDKMMEQKMKEEQERRKKKEMEERMSLEETKEQILKLQEKLSALQEEKHQLFLQLKKVLHEEEKRRRKEQSDLTTLTSAAYQQSLTVHTGTHLLSMQGSPGGHNRPGTLMAADRAKQMFGPQVLTTRHYVGSAAAFAGTPEHGQFQGSPGGAYGTAQPPPHYGPTQPAYSPSQQLRAPSAFPAVQYLSQPQPQPYAVHGHFQPTQTGFLQPGSTLSLQKQMEHANQQTSFSDSSSLRPMHPQALHPAPGLLASPQLPVQIQAAGKSGFATTSQPGPRLPFIQHSQNPRFYHK

36.7 kDa

(Note: Representative image - actual molecular weight may vary depending on tag type and expression method)

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