Q6NYC1 · JMJD6_HUMAN
- ProteinBifunctional arginine demethylase and lysyl-hydroxylase JMJD6
- GeneJMJD6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids403 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Plays a role in the regulation of nucleolar liquid-liquid phase separation (LLPS) by post-translationally modifying LIAT1 at its lysine-rich domain which inhibits LIAT1 nucleolar targeting (By similarity).
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:24360279, PubMed:24498420).
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).
Catalytic activity
- 2-oxoglutarate + L-lysyl-[protein] + O2 = (5S)-5-hydroxy-L-lysyl-[protein] + CO2 + succinate
- 2 2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + 2 O2 = 2 CO2 + 2 formaldehyde + L-arginyl-[protein] + 2 succinate
- 2-oxoglutarate + N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + O2 = CO2 + formaldehyde + N(omega)-methyl-L-arginyl-[protein] + succinate
- 2-oxoglutarate + a 5'-end methyltriphosphate-guanosine-ribonucleotide-snRNA + O2 = a 5'-end triphospho-guanosine-ribonucleotide-snRNA + CO2 + formaldehyde + H+ + succinate
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
39 μM | 2-oxoglutarate |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 184 | substrate | ||||
Sequence: T | ||||||
Binding site | 187 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 189 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 197 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 204 | substrate | ||||
Sequence: K | ||||||
Binding site | 273 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 285 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: T |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBifunctional arginine demethylase and lysyl-hydroxylase JMJD6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6NYC1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 85 | Decreases interaction with the NET domain of BRD4. | ||||
Sequence: W → A | ||||||
Mutagenesis | 90 | Nearly abolishes the interaction with the NET domain of BRD4. | ||||
Sequence: L → A | ||||||
Mutagenesis | 91 | Nearly abolishes the interaction with the NET domain of BRD4. | ||||
Sequence: K → A | ||||||
Mutagenesis | 95 | Nearly abolishes the interaction with the NET domain of BRD4. | ||||
Sequence: R → A | ||||||
Mutagenesis | 131 | Abolishes 2-oxoglutarate-binding and enzyme activity. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 187 | Loss of histone arginine demethylase and lysyl-hydroxylase activities. Abolishes homooligomerisation. Loss of arginine demethylase and a lysyl-hydroxylase activities; when associated with A-189 and A-273. | ||||
Sequence: H → A | ||||||
Mutagenesis | 189 | Loss of arginine demethylase and a lysyl-hydroxylase activities; when associated with A-187 and A-273. | ||||
Sequence: D → A | ||||||
Mutagenesis | 204 | Impairs enzyme activity without affecting 2-oxoglutarate-binding. | ||||
Sequence: K → A | ||||||
Mutagenesis | 231 | Impairs both hydroxylation activity and 2-oxoglutarate turnover assays. | ||||
Sequence: E → A | ||||||
Mutagenesis | 273 | Loss of arginine demethylase and a lysyl-hydroxylase activities; when associated with A-187 and A-189. | ||||
Sequence: H → A | ||||||
Mutagenesis | 285 | Impairs enzyme activity and 2-oxoglutarate-binding. | ||||
Sequence: T → A | ||||||
Mutagenesis | 287 | Impairs enzyme activity. | ||||
Sequence: N → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 435 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000129369 | 1-403 | UniProt | Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 | |||
Sequence: MNHKSKKRIREAKRSARPELKDSLDWTRHNYYESFSLSPAAVADNVERADALQLSVEEFVERYERPYKPVVLLNAQEGWSAQEKWTLERLKRKYRNQKFKCGEDNDGYSVKMKMKYYIEYMESTRDDSPLYIFDSSYGEHPKRRKLLEDYKVPKFFTDDLFQYAGEKRRPPYRWFVMGPPRSGTGIHIDPLGTSAWNALVQGHKRWCLFPTSTPRELIKVTRDEGGNQQDEAITWFNVIYPRTQLPTWPPEFKPLEILQKPGETVFVPGGWWHVVLNLDTTIAITQNFASSTNFPVVWHKTVRGRPKLSRKWYRILKQEHPELAVLADSVDLQESTGIASDSSSDSSSSSSSSSSDSDSECESGSEGDGTVHRRKKRRTCSMVGNGDTTSQDDCVSKERSSSR | |||||||
Modified residue (large scale data) | 23 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 38 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 38 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 136 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 379 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 381 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 390 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65 (PubMed:19574390).
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q6NYC1 | ARGLU1 Q9NWB6 | 4 | EBI-8464037, EBI-2808785 | |
BINARY | Q6NYC1 | BRD4 O60885 | 11 | EBI-8464037, EBI-723869 | |
BINARY | Q6NYC1 | CARM1 Q86X55 | 2 | EBI-8464037, EBI-2339854 | |
BINARY | Q6NYC1 | CCNL1 Q9UK58 | 3 | EBI-8464037, EBI-2836773 | |
BINARY | Q6NYC1 | CDK9 P50750 | 5 | EBI-8464037, EBI-1383449 | |
BINARY | Q6NYC1 | ESR1 P03372 | 8 | EBI-8464037, EBI-78473 | |
BINARY | Q6NYC1 | FRMD6 Q96NE9 | 3 | EBI-8464037, EBI-741729 | |
BINARY | Q6NYC1 | JMJD6 Q6NYC1 | 3 | EBI-8464037, EBI-8464037 | |
BINARY | Q6NYC1 | NAA50 Q9GZZ1 | 6 | EBI-8464037, EBI-1052523 | |
BINARY | Q6NYC1 | PRPF38A Q8NAV1 | 5 | EBI-8464037, EBI-715374 | |
BINARY | Q6NYC1 | RSRC1 Q96IZ7 | 4 | EBI-8464037, EBI-712189 | |
BINARY | Q6NYC1 | TP53 P04637 | 7 | EBI-8464037, EBI-366083 | |
BINARY | Q6NYC1 | U2AF1 Q01081 | 4 | EBI-8464037, EBI-632461 | |
BINARY | Q6NYC1 | ZCCHC17 Q9NP64 | 6 | EBI-8464037, EBI-746345 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 6-10 | Nuclear localization signal 1 | ||||
Sequence: KKRIR | ||||||
Motif | 91-95 | Nuclear localization signal 2 | ||||
Sequence: KRKYR | ||||||
Motif | 141-145 | Nuclear localization signal 3 | ||||
Sequence: PKRRK | ||||||
Domain | 141-305 | JmjC | ||||
Sequence: PKRRKLLEDYKVPKFFTDDLFQYAGEKRRPPYRWFVMGPPRSGTGIHIDPLGTSAWNALVQGHKRWCLFPTSTPRELIKVTRDEGGNQQDEAITWFNVIYPRTQLPTWPPEFKPLEILQKPGETVFVPGGWWHVVLNLDTTIAITQNFASSTNFPVVWHKTVRGR | ||||||
Motif | 167-170 | Nuclear localization signal 4 | ||||
Sequence: KRRP | ||||||
Compositional bias | 336-360 | Polar residues | ||||
Sequence: TGIASDSSSDSSSSSSSSSSDSDSE | ||||||
Region | 336-403 | Disordered | ||||
Sequence: TGIASDSSSDSSSSSSSSSSDSDSECESGSEGDGTVHRRKKRRTCSMVGNGDTTSQDDCVSKERSSSR | ||||||
Motif | 373-378 | Nuclear localization signal 5 | ||||
Sequence: RRKKRR |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q6NYC1-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsAlpha
- Length403
- Mass (Da)46,462
- Last updated2004-07-05 v1
- Checksum9C9AADA98B24B035
Q6NYC1-2
- Name2
- SynonymsBeta
Q6NYC1-3
- Name3
- Differences from canonical
- 403-403: R → RIRDTCGGRAHP
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 136 | in Ref. 3; BAG51050 | ||||
Sequence: S → G | ||||||
Compositional bias | 336-360 | Polar residues | ||||
Sequence: TGIASDSSSDSSSSSSSSSSDSDSE | ||||||
Alternative sequence | VSP_014022 | 361-402 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_014023 | 403 | in isoform 2 and isoform 3 | |||
Sequence: R → RIRDTCGGRAHP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB073711 EMBL· GenBank· DDBJ | BAC16755.1 EMBL· GenBank· DDBJ | mRNA | ||
AB011157 EMBL· GenBank· DDBJ | BAA25511.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK021780 EMBL· GenBank· DDBJ | BAG51050.1 EMBL· GenBank· DDBJ | mRNA | ||
AK294816 EMBL· GenBank· DDBJ | BAG57932.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005837 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471099 EMBL· GenBank· DDBJ | EAW89434.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC047003 EMBL· GenBank· DDBJ | AAH47003.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC066654 EMBL· GenBank· DDBJ | AAH66654.1 EMBL· GenBank· DDBJ | mRNA |