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UniProt functional annotation for Q9UBK2 | ||
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| UniProt code: Q9UBK2. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. Also involved in the integration of the circadian rhythms and energy metabolism. Required for oscillatory expression of clock genes, such as ARNTL/BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK. {ECO:0000269|PubMed:10713165, ECO:0000269|PubMed:20005308, ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:23836911}. |
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| Subunit: | |
Homooligomer. Interacts with MYBBP1A; inhibits MYBBP1A transcriptional activation (By similarity). Interacts with PRDM16, LPIN1 and PML (By similarity). Interacts (via LXXLL motif) with RORA and RORC (via AF-2 motif); activates RORA and RORC transcriptional activation (By similarity). Interacts with LRPPRC. Interacts with RNF34 (via RING-type zinc finger). {ECO:0000250|UniProtKB:O70343, ECO:0000269|PubMed:10713165, ECO:0000269|PubMed:17050673, ECO:0000269|PubMed:22064484}. |
| Subcellular location: | |
[Isoform 1]: Nucleus. Nucleus, PML body. |
| Subcellular location: | |
[Isoform B4]: Nucleus. |
| Subcellular location: | |
[Isoform B4-8a]: Cytoplasm. Nucleus. |
| Subcellular location: | |
[Isoform B5]: Nucleus. Nucleus, PML body. |
| Subcellular location: | |
[Isoform 9]: Nucleus {ECO:0000269|PubMed:22009745}. |
| Tissue specificity: | |
Heart, skeletal muscle, liver and kidney. Expressed at lower levels in brain and pancreas and at very low levels in the intestine and white adipose tissue. In skeletal muscle, levels were lower in obese than in lean subjects and fasting induced a 2-fold increase in levels in the skeletal muscle in obese subjects. {ECO:0000269|PubMed:10585775, ECO:0000269|PubMed:10643692, ECO:0000269|PubMed:10713165}. |
| Induction: | |
Transcription is repressed by ZNF746 which binds to 'insulin response sequences' its promoter. {ECO:0000269|PubMed:21376232}. |
| Ptm: | |
Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter. Phosphorylated by CLK2. {ECO:0000250}. |
| Ptm: | |
Heavily acetylated by GCN5 and biologically inactive under conditions of high nutrients. Deacetylated by SIRT1 in low nutrients/high NAD conditions. |
| Ptm: | |
Ubiquitinated. Ubiquitination by RNF34 induces proteasomal degradation. {ECO:0000269|PubMed:22064484}. |
| Miscellaneous: | |
[Isoform B5]: Produced by alternative promoter usage. {ECO:0000305}. |
| Miscellaneous: | |
[Isoform B4]: Produced by alternative promoter usage. {ECO:0000305}. |
| Miscellaneous: | |
[Isoform B4-8a]: Produced by alternative promoter usage. {ECO:0000305}. |
| Miscellaneous: | |
[Isoform B5-NT]: Produced by alternative promoter usage. {ECO:0000305}. |
| Miscellaneous: | |
[Isoform B4-3ext]: Produced by alternative promoter usage. {ECO:0000305}. |
| Miscellaneous: | |
[Isoform 9]: Produced by alternative promoter usage. May be involved in gluconeogenesis, liver-specific. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.