UniProt functional annotation for O00482



	UniProt functional annotation for O00482

UniProt code: O00482.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti- inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. Activates the transcription of CYP2C38 (By similarity). {ECO:0000250|UniProtKB:P45448, ECO:0000269|PubMed:15707893, ECO:0000269|PubMed:15723037, ECO:0000269|PubMed:15897460, ECO:0000269|PubMed:16289203, ECO:0000269|PubMed:20159957}.

Subunit: Binds DNA as a monomer (By similarity). Interacts with GRIP1, NCOA2 and NR0B2 (PubMed:15707893, PubMed:15723037, PubMed:15897460, PubMed:16289203). Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). {ECO:0000250, ECO:0000269|PubMed:15707893, ECO:0000269|PubMed:15723037, ECO:0000269|PubMed:15897460, ECO:0000269|PubMed:16289203, ECO:0000269|PubMed:20159957}.

Subcellular location: Nucleus {ECO:0000305}.

Tissue specificity: Abundantly expressed in pancreas, less in liver, very low levels in heart and lung. Expressed in the Hep-G2 cell line. Isoform 1 and isoform 2 seem to be present in fetal and adult liver and Hep-G2 cells.

Ptm: Sumoylated by SUMO1 at Lys-270 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation. {ECO:0000269|PubMed:20159957}.

Miscellaneous: [Isoform 3]: Does not induce CYP7A promoter activity. {ECO:0000305}.

Similarity: Belongs to the nuclear hormone receptor family. NR5 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti- inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. Activates the transcription of CYP2C38 (By similarity). {ECO:0000250\|UniProtKB:P45448, ECO:0000269\|PubMed:15707893, ECO:0000269\|PubMed:15723037, ECO:0000269\|PubMed:15897460, ECO:0000269\|PubMed:16289203, ECO:0000269\|PubMed:20159957}.


Subunit:		Binds DNA as a monomer (By similarity). Interacts with GRIP1, NCOA2 and NR0B2 (PubMed:15707893, PubMed:15723037, PubMed:15897460, PubMed:16289203). Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). {ECO:0000250, ECO:0000269\|PubMed:15707893, ECO:0000269\|PubMed:15723037, ECO:0000269\|PubMed:15897460, ECO:0000269\|PubMed:16289203, ECO:0000269\|PubMed:20159957}.
Subcellular location:		Nucleus {ECO:0000305}.
Tissue specificity:		Abundantly expressed in pancreas, less in liver, very low levels in heart and lung. Expressed in the Hep-G2 cell line. Isoform 1 and isoform 2 seem to be present in fetal and adult liver and Hep-G2 cells.
Ptm:		Sumoylated by SUMO1 at Lys-270 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation. {ECO:0000269\|PubMed:20159957}.
Miscellaneous:		[Isoform 3]: Does not induce CYP7A promoter activity. {ECO:0000305}.
Similarity:		Belongs to the nuclear hormone receptor family. NR5 subfamily. {ECO:0000305}.