JMJD6 Dioxygenase that can both act as a arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. Hydroxylates its own N-terminus, which is required for homooligomerization. In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which preferentially demethylates asymmetric dimethylation. 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. However, histone arginine demethylation may not constitute the primary activity in vivo. 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. Demethylates other arginine methylated-proteins such as ESR1. Has no histone lysine demethylase activity. 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/U2AF65. Seems to be necessary for the regulation of macrophage cytokine responses. Belongs to the JMJD6 family. Highly expressed in the heart, skeletal muscle and kidney. Expressed at moderate or low level in brain, placenta, lung, liver, pancreas, spleen, thymus, prostate, testis and ovary. Up-regulated in many patients with chronic pancreatitis. Expressed in nursing thymic epithelial cells. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; Cell development/differentiation; EC 1.14.11.-; Nucleolus; Oxidoreductase; Receptor, misc.
Chromosomal Location of Human Ortholog: 17q25.1
Cellular Component:  cytoplasm; cytosol; nucleolus; nucleoplasm; nucleus; plasma membrane; ribonucleoprotein complex
Molecular Function:  demethylase activity; histone demethylase activity; histone demethylase activity (H3-R2 specific); histone demethylase activity (H4-R3 specific); identical protein binding; iron ion binding; oxidative RNA demethylase activity; P-TEFb complex binding; peptidyl-lysine 5-dioxygenase activity; protein binding; protein homodimerization activity; RNA binding; signaling receptor activity; single-stranded RNA binding; transcription coactivator activity
Biological Process:  cell surface receptor signaling pathway; erythrocyte development; heart development; histone H3-R2 demethylation; histone H4-R3 demethylation; kidney development; lung development; macrophage activation; mRNA processing; oxidative RNA demethylation; peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; positive regulation of transcription by RNA polymerase II; positive regulation of transcription, DNA-templated; protein demethylation; protein homooligomerization; recognition of apoptotic cell; regulation of mRNA splicing, via spliceosome; retina development in camera-type eye; RNA splicing; sprouting angiogenesis; T cell differentiation in thymus
Reference #:  Q6NYC1 (UniProtKB)
Alt. Names/Synonyms: Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6; Histone arginine demethylase JMJD6; JmjC domain-containing protein 6; JMJD6; jumonji domain containing 6; Jumonji domain-containing protein 6; KIAA0585; Lysyl-hydroxylase JMJD6; Peptide-lysine 5-dioxygenase JMJD6; Phosphatidylserine receptor; Protein PTDSR; PSR; PTDSR; PTDSR1
Gene Symbols: JMJD6
Molecular weight: 46,462 Da
Basal Isoelectric point: 8.84  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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JMJD6

Protein Structure Not Found.


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