UniProt functional annotation for Q14865



	UniProt functional annotation for Q14865

UniProt code: Q14865.

Organism: Homo sapiens (Human).

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

Function: Transcription coactivator that binds to the 5'-AATA[CT]-3' core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-336, leading to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation. Represses the cytomegalovirus enhancer. {ECO:0000269|PubMed:21532585}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00355}.

Tissue specificity: Widely expressed, including in liver (at protein level). {ECO:0000269|PubMed:21532585}.

Domain: The ARID domain mediates the interaction with DNA.

Ptm: Methylation at Lys-336 prevents DNA-binding. Demethylation by PHF2 promotes recruitment of the PHF2-ARID5B complex to promoters. {ECO:0000269|PubMed:21532585}.

Disease: Note=Defects in ARID5B may be a cause of susceptibility to coronary atherosclerosis in the Japanese population.

Disease: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269|PubMed:19684603, ECO:0000269|PubMed:19684604, ECO:0000269|PubMed:20042726, ECO:0000269|PubMed:20054350, ECO:0000269|PubMed:20189245, ECO:0000269|PubMed:20460642, ECO:0000269|PubMed:21098271}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the ARID5B family. {ECO:0000305}.

Sequence caution: Sequence=AAH15120.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH36831.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH66345.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAI07801.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB15012.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={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:		Transcription coactivator that binds to the 5'-AATA[CT]-3' core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-336, leading to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation. Represses the cytomegalovirus enhancer. {ECO:0000269\|PubMed:21532585}.


Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00355}.
Tissue specificity:		Widely expressed, including in liver (at protein level). {ECO:0000269\|PubMed:21532585}.
Domain:		The ARID domain mediates the interaction with DNA.
Ptm:		Methylation at Lys-336 prevents DNA-binding. Demethylation by PHF2 promotes recruitment of the PHF2-ARID5B complex to promoters. {ECO:0000269\|PubMed:21532585}.
Disease:		Note=Defects in ARID5B may be a cause of susceptibility to coronary atherosclerosis in the Japanese population.
Disease:		Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269\|PubMed:19684603, ECO:0000269\|PubMed:19684604, ECO:0000269\|PubMed:20042726, ECO:0000269\|PubMed:20054350, ECO:0000269\|PubMed:20189245, ECO:0000269\|PubMed:20460642, ECO:0000269\|PubMed:21098271}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the ARID5B family. {ECO:0000305}.
Sequence caution:		Sequence=AAH15120.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH36831.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH66345.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAI07801.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB15012.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};