JMJD6

This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins are predicted to function as protein hydroxylases or histone demethylases. This protein was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells; however, subsequent studies have indicated that it does not directly function in the clearance of apoptotic cells, and questioned whether it is a true phosphatidylserine receptor. Multiple transcript variants encoding different isoforms have been found for this gene.

jumonji domain containing 6, arginine demethylase and lysine hydroxylase

Dioxygenase that can both act as a arginine demethylase and a lysyl-hydroxylase (PubMed:24498420, PubMed:17947579, PubMed:20684070, PubMed:21060799, PubMed:22189873).
Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/AC U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/AC U2AF65, affecting the pre-mRNA splicing activity of U2AF2/AC U2AF65 (PubMed:19574390).
Hydroxylates its own N-terminus, which is required for homooligomerization (PubMed:22189873).
In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA (PubMed:20679243, PubMed:29176719).
Also acts as an arginine demethylase which preferentially demethylates asymmetric dimethylation (PubMed:17947579, PubMed:24498420, PubMed:24360279).
Demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), including mono-, symmetric di- and asymmetric dimethylated forms, thereby playing a role in histone code (PubMed:17947579, PubMed:24360279).
However, histone arginine demethylation may not constitute the primary activity in vivo (PubMed:17947579, PubMed:21060799, PubMed:22189873).
In collaboration with BRD4, interacts with the positive transcription elongation factor b (P-TEFb) complex in its active form to regulate polymerase II promoter-proximal pause release for transcriptional activation of a large cohort of genes. On distal enhancers, so called anti-pause enhancers, demethylates both histone H4R3me2 and the methyl cap of 7SKsnRNA leading to the dismissal of the 7SKsnRNA:HEXIM1 inhibitor complex. After removal of repressive marks, the complex BRD4:JMJD6 attract and retain the P-TEFb complex on chromatin, leading to its activation, promoter-proximal polymerase II pause release, and transcriptional activation (PubMed:24360279).
Demethylates other arginine methylated-proteins such as ESR1 (PubMed:24498420).
Has no histone lysine demethylase activity (PubMed:21060799).
Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/AC U2AF65 (By similarity).
Seems to be necessary for the regulation of macrophage cytokine responses (PubMed:15622002).

Cell surface receptor signaling pathwayIEA:Ensembl
Chromatin organizationIEA:UniProtKB-KW
Erythrocyte developmentIEA:Ensembl
Heart developmentIEA:Ensembl
Histone H3-R2 demethylationManual Assertion Based On ExperimentIDA:BHF-UCL
Histone H4-R3 demethylationManual Assertion Based On ExperimentIDA:UniProtKB
Kidney developmentIEA:Ensembl
Lung developmentIEA:Ensembl
Macrophage activationIEA:Ensembl
mRNA processingIEA:UniProtKB-KW
Oxidative RNA demethylationManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-lysine hydroxylation to 5-hydroxy-L-lysineManual Assertion Based On ExperimentIDA:UniProtKB
PhagocytosisManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:UniProtKB
Protein demethylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein homooligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Recognition of apoptotic cellIEA:Ensembl
Regulation of mRNA splicing, via spliceosomeManual Assertion Based On ExperimentIMP:UniProtKB
Retina development in camera-type eyeIEA:Ensembl
RNA splicingIEA:UniProtKB-KW
Sprouting angiogenesisISS:UniProtKB
T cell differentiation in thymusIEA:Ensembl

Nucleus, nucleoplasm; Nucleus, nucleolus; Cytoplasm. Mainly found throughout the nucleoplasm outside of regions containing heterochromatic DNA, with some localization in nucleolus. During mitosis, excluded from the nucleus and reappears in the telophase of the cell cycle.

Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization.