UniProt functional annotation for Q6NYC1



	UniProt functional annotation for Q6NYC1

UniProt code: Q6NYC1.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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/U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/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/U2AF65 (By similarity). Seems to be necessary for the regulation of macrophage cytokine responses (PubMed:15622002). {ECO:0000250|UniProtKB:Q9ERI5, ECO:0000269|PubMed:15622002, ECO:0000269|PubMed:17947579, ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:20679243, ECO:0000269|PubMed:20684070, ECO:0000269|PubMed:21060799, ECO:0000269|PubMed:22189873, ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:24498420, ECO:0000269|PubMed:29176719}.

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:0000269|PubMed:19574390, ECO:0000269|PubMed:20684070, ECO:0000269|PubMed:22189873};

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:0000269|PubMed:17947579, ECO:0000269|PubMed:24360279};

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:0000269|PubMed:17947579, ECO:0000269|PubMed:24360279};

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:0000269|PubMed:24360279};

Cofactor: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:22189873}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19574390};

Biophysicochemical properties: Kinetic parameters: KM=39 uM for 2-oxoglutarate {ECO:0000269|PubMed:20684070};

Subunit: Homooligomerizes; requires lysyl-hydroxylase activity (PubMed:22189873, PubMed:24360279). Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65 (PubMed:19574390). Interacts with LIAT1 (By similarity). Interacts with CDK9 and CCNT1; the interaction is direct with CDK9 and associates the P-TEFb complex when active (PubMed:24360279). Interacts (via JmjC and N-terminal domains) with BRD4 (via NET domain); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers (PubMed:21555454, PubMed:24360279, PubMed:29176719). {ECO:0000250|UniProtKB:Q9ERI5, ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:21555454, ECO:0000269|PubMed:22189873, ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:29176719}.

Subcellular location: Nucleus, nucleoplasm {ECO:0000269|PubMed:14729065, ECO:0000269|PubMed:21060799}. Nucleus, nucleolus {ECO:0000269|PubMed:21060799}. Cytoplasm {ECO:0000269|PubMed:21060799, ECO:0000269|PubMed:24498420}. Note=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. {ECO:0000269|PubMed:21060799}.

Tissue specificity: 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. {ECO:0000269|PubMed:15072554, ECO:0000269|PubMed:15622002, ECO:0000269|PubMed:9628581}.

Induction: Up-regulated upon cytokine treatment, but not upon TNF treatment. {ECO:0000269|PubMed:15072554}.

Domain: The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus. {ECO:0000269|PubMed:14729065}.

Ptm: Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization. {ECO:0000269|PubMed:22189873}.

Similarity: Belongs to the JMJD6 family. {ECO:0000305}.

Sequence caution: Sequence=AAH47003.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAA25511.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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/U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/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/U2AF65 (By similarity). Seems to be necessary for the regulation of macrophage cytokine responses (PubMed:15622002). {ECO:0000250\|UniProtKB:Q9ERI5, ECO:0000269\|PubMed:15622002, ECO:0000269\|PubMed:17947579, ECO:0000269\|PubMed:19574390, ECO:0000269\|PubMed:20679243, ECO:0000269\|PubMed:20684070, ECO:0000269\|PubMed:21060799, ECO:0000269\|PubMed:22189873, ECO:0000269\|PubMed:24360279, ECO:0000269\|PubMed:24498420, ECO:0000269\|PubMed:29176719}.


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:0000269\|PubMed:19574390, ECO:0000269\|PubMed:20684070, ECO:0000269\|PubMed:22189873};
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:0000269\|PubMed:17947579, ECO:0000269\|PubMed:24360279};
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:0000269\|PubMed:17947579, ECO:0000269\|PubMed:24360279};
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:0000269\|PubMed:24360279};
Cofactor:		Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269\|PubMed:19574390, ECO:0000269\|PubMed:22189873}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269\|PubMed:19574390};
Biophysicochemical properties:		Kinetic parameters: KM=39 uM for 2-oxoglutarate {ECO:0000269\|PubMed:20684070};
Subunit:		Homooligomerizes; requires lysyl-hydroxylase activity (PubMed:22189873, PubMed:24360279). Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65 (PubMed:19574390). Interacts with LIAT1 (By similarity). Interacts with CDK9 and CCNT1; the interaction is direct with CDK9 and associates the P-TEFb complex when active (PubMed:24360279). Interacts (via JmjC and N-terminal domains) with BRD4 (via NET domain); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers (PubMed:21555454, PubMed:24360279, PubMed:29176719). {ECO:0000250\|UniProtKB:Q9ERI5, ECO:0000269\|PubMed:19574390, ECO:0000269\|PubMed:21555454, ECO:0000269\|PubMed:22189873, ECO:0000269\|PubMed:24360279, ECO:0000269\|PubMed:29176719}.
Subcellular location:		Nucleus, nucleoplasm {ECO:0000269\|PubMed:14729065, ECO:0000269\|PubMed:21060799}. Nucleus, nucleolus {ECO:0000269\|PubMed:21060799}. Cytoplasm {ECO:0000269\|PubMed:21060799, ECO:0000269\|PubMed:24498420}. Note=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. {ECO:0000269\|PubMed:21060799}.
Tissue specificity:		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. {ECO:0000269\|PubMed:15072554, ECO:0000269\|PubMed:15622002, ECO:0000269\|PubMed:9628581}.
Induction:		Up-regulated upon cytokine treatment, but not upon TNF treatment. {ECO:0000269\|PubMed:15072554}.
Domain:		The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus. {ECO:0000269\|PubMed:14729065}.
Ptm:		Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization. {ECO:0000269\|PubMed:22189873}.
Similarity:		Belongs to the JMJD6 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH47003.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAA25511.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};