JMJD6
JMJD6 is a nuclear iron (II) and 2-oxoglutarate dependent dioxygenase that acts as both an arginine demethylase and a lysyl-hydroxylase. It is also known as PTDSR, PTDSR1 and KIAA0585, reflecting its earlier description as a phosphatidylserine receptor. Browse Assay Genie's current range of JMJD6 research reagents below, or read on for the biology behind the target.
JMJD6 is a dioxygenase with two described catalytic activities. As a lysyl-hydroxylase it catalyses 5-hydroxylation of specific lysine residues on target proteins such as U2AF2/U2AF65 and LUC7L2, and by modifying U2AF2/U2AF65 it regulates pre-mRNA splicing. It also hydroxylates its own N-terminus, which is required for homooligomerisation. It may act as an RNA hydroxylase too, as suggested by its ability to bind single-stranded RNA. As an arginine demethylase it preferentially removes asymmetric dimethylation, acting on histone H3 at Arg-2 and histone H4 at Arg-3 and on other methylated proteins such as ESR1. It has no histone lysine demethylase activity, and histone arginine demethylation may not be its primary activity in vivo.
In transcription, JMJD6 works with BRD4 and interacts with the P-TEFb complex to regulate release of polymerase II from promoter-proximal pausing. At distal anti-pause enhancers it demethylates histone H4R3me2 and the methyl cap of 7SK snRNA, leading to dismissal of the 7SK snRNA:HEXIM1 inhibitor complex. It also regulates nucleolar liquid-liquid phase separation by modifying LIAT1 at its lysine-rich domain, which inhibits LIAT1 nucleolar targeting. The protein is found in the nucleoplasm, nucleolus and cytoplasm, and belongs to the JMJD6 family within the iron (II) and 2-oxoglutarate dependent oxygenases. The JMJD6 gene has mouse and rat orthologs, both named Jmjd6.
JMJD6 was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells. Later studies indicated that it does not directly function in clearing apoptotic cells and questioned whether it is a true phosphatidylserine receptor. It is required for differentiation of multiple organs during embryogenesis, acts as a regulator of haematopoietic differentiation, and is needed for angiogenic sprouting through its control of U2AF2/U2AF65 splicing activity. It also appears necessary for macrophage cytokine responses. Multiple transcript variants encoding different isoforms have been reported.
JMJD6 hydroxylates U2AF2/U2AF65 and LUC7L2, linking lysine hydroxylation to the control of pre-mRNA splicing.
With BRD4 and P-TEFb, JMJD6 helps release promoter-proximal polymerase II pausing by demethylating H4R3me2 and 7SK snRNA.
JMJD6 demethylates arginine marks on histones H3 and H4, making it a subject of study in histone arginine methylation.
JMJD6 is required for organ differentiation in embryogenesis, haematopoietic differentiation and angiogenic sprouting.
JMJD6 is a dioxygenase that hydroxylates lysine residues on proteins such as U2AF2/U2AF65 and LUC7L2, thereby influencing RNA splicing. It also demethylates arginine residues, including histone H3R2 and H4R3, and works with BRD4 and P-TEFb to promote polymerase II pause release.
JMJD6 was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells, hence the symbols PTDSR and PTDSR1. Later studies showed it does not directly clear apoptotic cells and questioned this role. KIAA0585 is another alias for the gene.
Mouse and rat both have a Jmjd6 ortholog of the human gene. In humans, multiple transcript variants encoding different isoforms have been described. Check the datasheet of any product for its validated reactivity.
Splicing factors, transcription elongation regulators and other proteins linked to JMJD6 activity.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q6NYC1; product specifications from Assay Genie datasheets.