JMJD6

Description

The JMJD6 (jumonji domain containing 6, arginine demethylase and lysine hydroxylase) is a protein-coding gene located on chromosome 17.

JMJD6 is a human gene that encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins belong to the alpha-ketoglutarate-dependent hydroxylase superfamily and are predicted to function as protein hydroxylases or histone demethylases. JMJD6 was initially identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells, but subsequent studies suggest it may not directly function in this process. Multiple transcript variants encoding different isoforms have been found for this gene. JMJD6 plays a role in angiogenesis, the process of vessel formation. Elevated JMJD6 levels are associated with aggressiveness and metastasis in breast cancer in mice, implicating its role in mammary tumorigenesis.

JMJD6 is a dioxygenase that acts as both an arginine demethylase and a lysyl-hydroxylase. It catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2, regulating RNA splicing by affecting the pre-mRNA splicing activity of U2AF2/U2AF65. JMJD6 also hydroxylates its own N-terminus, which is required for homooligomerization. In addition to its peptidyl-lysine 5-dioxygenase activity, JMJD6 may act as an RNA hydroxylase, as it can bind single strand RNA. JMJD6 preferentially demethylates asymmetric dimethylation, acting as an arginine demethylase that demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), including mono-, symmetric di- and asymmetric dimethylated forms. However, histone arginine demethylation may not be its primary activity in vivo. JMJD6 interacts with BRD4 and the positive transcription elongation factor b (P-TEFb) complex, regulating polymerase II promoter-proximal pause release for transcriptional activation of a large cohort of genes. It demethylates both histone H4R3me2 and the methyl cap of 7SKsnRNA on distal enhancers, leading to the dismissal of the 7SKsnRNA:HEXIM1 inhibitor complex and activation of the P-TEFb complex, promoting transcriptional activation. JMJD6 also demethylates other arginine methylated-proteins such as ESR1 and lacks histone lysine demethylase activity. It is required for differentiation of multiple organs during embryogenesis and is a key regulator of hematopoietic differentiation, required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65. JMJD6 seems to be necessary for the regulation of macrophage cytokine responses. It homooligomerizes, requiring lysyl-hydroxylase activity, and interacts with LUC7L2, LUC7L3, U2AF2/U2AF65, CDK9, CCNT1, and BRD4.

JMJD6 is also known as PSR, PTDSR, PTDSR1.

Associated Diseases

WES Whole Exome Sequencing