JMJD6: Dioxygenase that can both act as a histone 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. Acts as a regulator of RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. In addition to peptidyl-lysine 5-dioxygenase activity, may act as a RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. 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. 3 isoforms of the human protein are produced by alternative splicing.
Protein type: Nucleolus; EC 1.14.11.-; Apoptosis; Cell development/differentiation; Receptor, misc.; Oxidoreductase
Chromosomal Location of Human Ortholog: 17q25
Cellular Component: nucleoplasm; nucleolus; plasma membrane; nucleus
Molecular Function: identical protein binding; protein binding; single-stranded RNA binding; histone demethylase activity (H4-R3 specific); RNA binding; iron ion binding; receptor activity; histone demethylase activity (H3-R2 specific)
Biological Process: erythrocyte development; transcription, DNA-dependent; RNA splicing; heart development; T cell differentiation in the thymus; recognition of apoptotic cell; peptidyl-lysine hydroxylation to 5-hydroxy-L-lysine; macrophage activation; regulation of nuclear mRNA splicing, via spliceosome; cell surface receptor linked signal transduction; regulation of transcription, DNA-dependent; retina development in camera-type eye; sprouting angiogenesis; kidney development; mRNA processing; lung development
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