UniProt ID: Q6PFM0
FUNCTION: 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. Demethylates other arginine methylated-proteins such as esr1. Has no histone lysine demethylase activity (By similarity). Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation (By similarity). {ECO:0000250|UniProtKB:Q6NYC1, ECO:0000250|UniProtKB:Q9ERI5}.
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-lysyl-[protein] + O2 = (5S)-5-hydroxy- L-lysyl-[protein] + CO2 + succinate; Xref=Rhea:RHEA:58360, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15144, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031, ChEBI:CHEBI:141843; Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CATALYTIC ACTIVITY: Reaction=2 2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl- [protein] + 2 O2 = 2 CO2 + 2 formaldehyde + L-arginyl-[protein] + 2 succinate; Xref=Rhea:RHEA:58348, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:11992, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:29965, ChEBI:CHEBI:30031, ChEBI:CHEBI:88221; Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl- [protein] + O2 = CO2 + formaldehyde + N(omega)-methyl-L-arginyl- [protein] + succinate; Xref=Rhea:RHEA:58472, Rhea:RHEA- COMP:11990, Rhea:RHEA-COMP:11992, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:65280, ChEBI:CHEBI:88221; Evidence={ECO:0000250|UniProtKB:Q6NYC1};
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + a 5'-methyltriphosphate-guanosine- ribonucleotide-snRNA + O2 = a 5'-triphospho-guanosine- ribonucleotide-snRNA + CO2 + formaldehyde + H(+) + succinate; Xref=Rhea:RHEA:58784, Rhea:RHEA-COMP:15220, Rhea:RHEA- COMP:15221, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:138278, ChEBI:CHEBI:142789; Evidence={ECO:0000250|UniProtKB:Q6NYC1};
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q6NYC1}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6NYC1};
SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q6NYC1}. Nucleus, nucleolus {ECO:0000250|UniProtKB:Q6NYC1}. Cytoplasm {ECO:0000250|UniProtKB:Q6NYC1}.
TISSUE SPECIFICITY: After the somite segmentation period, it is apparent throughout the embryo and the hatching gland. At the larval (3 dpf) stage, it is detected in the heart and kidney. {ECO:0000269|PubMed:15469976}.
DEVELOPMENTAL STAGE: Expressed in embryos from the one-cell developmental stage to the 3 days post-fertilization (dpf) larval stage. {ECO:0000269|PubMed:15469976}.
DOMAIN: The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus. {ECO:0000250|UniProtKB:Q6NYC1}.
PTM: Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization. {ECO:0000250|UniProtKB:Q6NYC1}.
DISRUPTION PHENOTYPE: Fishes display an accumulation of a large number of dead apoptotic cells in whole early embryo. These cells interfere with embryonic cell migration. In addition, normal development of the somite, brain, heart and notochord are sequentially disrupted up to 24 hours post-fertilization. {ECO:0000269|PubMed:15469976}.
SIMILARITY: Belongs to the JMJD6 family. {ECO:0000305}.
CAUTION: Was initially thought to constitute the phosphatidylserine receptor, a receptor that mediates recognition of phosphatidylserine, a specific marker only present at the surface of apoptotic cells, and participates in apoptotic cell phagocytosis. However, some results strongly suggest that it does not constitute the receptor for phosphatidylserine and is not involved in apoptotic cell removal. {ECO:0000305}.
This information was provided by UniProt through a collaboration with ZFIN. (1)