Enables histone H3-methyl-lysine-36 demethylase activity and histone H3-methyl-lysine-9 demethylase activity. Involved in histone H3-K36 demethylation and histone H3-K9 demethylation. Located in cytosol and nucleoplasm. Implicated in autosomal dominant non-syndromic intellectual disability; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]
Function:
Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.
Subcellular Location:
Nucleus. Chromosome. Associates with euchromatic regions. Does not associate with heterochromatin.
Tissue Specificity:
Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow.
Post-translational modifications:
Methylated at Lys-185; automethylated.
Similarity:
Belongs to the JHDM3 histone demethylase family.
Contains 1 JmjC domain.
Contains 1 JmjN domain.
Contains 2 PHD-type zinc fingers.
Contains 2 Tudor domains.
SWISS:
O94953
Gene ID:
23030
Database links:
Entrez Gene: 23030 Human
Entrez Gene: 193796 Mouse
SwissProt: O94953 Human
SwissProt: Q91VY5 Mouse
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