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Protein

Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6

Gene

JMJD6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 an 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.4 Publications

Cofactori

Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication

Kineticsi

  1. KM=39 µM for 2-oxoglutarate1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei184SubstrateBy similarity1
    Metal bindingi187Iron; catalytic1
    Metal bindingi189Iron; catalytic1
    Binding sitei1972-oxoglutarate1 Publication1
    Binding sitei204SubstrateBy similarity1
    Metal bindingi273Iron; catalytic1
    Binding sitei2852-oxoglutarate1 Publication1

    GO - Molecular functioni

    • histone demethylase activity Source: Reactome
    • histone demethylase activity (H3-R2 specific) Source: UniProtKB
    • histone demethylase activity (H4-R3 specific) Source: UniProtKB
    • identical protein binding Source: IntAct
    • iron ion binding Source: UniProtKB
    • peptidyl-lysine 5-dioxygenase activity Source: UniProtKB
    • receptor activity Source: Ensembl
    • RNA binding Source: UniProtKB
    • single-stranded RNA binding Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Chromatin regulator, Developmental protein, Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Differentiation, mRNA processing, mRNA splicing, Transcription, Transcription regulation

    Keywords - Ligandi

    Iron, Metal-binding, RNA-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS12211-MONOMER.
    BRENDAi1.14.11.4. 2681.
    ReactomeiR-HSA-3214842. HDMs demethylate histones.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (EC:1.14.11.-)
    Alternative name(s):
    Histone arginine demethylase JMJD6
    JmjC domain-containing protein 6
    Jumonji domain-containing protein 6
    Lysyl-hydroxylase JMJD6
    Peptide-lysine 5-dioxygenase JMJD6
    Phosphatidylserine receptor
    Short name:
    Protein PTDSR
    Gene namesi
    Name:JMJD6
    Synonyms:KIAA0585, PTDSR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:19355. JMJD6.

    Subcellular locationi

    • Nucleusnucleoplasm
    • Nucleusnucleolus

    • 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.

    GO - Cellular componenti

    • cytosol Source: Ensembl
    • intracellular ribonucleoprotein complex Source: Ensembl
    • nucleolus Source: UniProtKB
    • nucleoplasm Source: UniProtKB
    • nucleus Source: UniProtKB
    • plasma membrane Source: Ensembl
    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi131Y → F: Abolishes 2-oxoglutarate-binding and enzyme activity. 1 Publication1
    Mutagenesisi187H → A: Loss of catalytic activity; when associated with A-189 and A-273. 2 Publications1
    Mutagenesisi189D → A: Loss of catalytic activity; when associated with A-187 and A-273. 2 Publications1
    Mutagenesisi204K → A: Impairs enzyme activity without affecting 2-oxoglutarate-binding. 1 Publication1
    Mutagenesisi231E → A: Impairs both hydroxylation activity and 2-oxoglutarate turnover assays. 1 Publication1
    Mutagenesisi273H → A: Loss of catalytic activity; when associated with A-187 and A-189. 1 Publication1
    Mutagenesisi285T → A: Impairs enzyme activity and 2-oxoglutarate-binding. 1 Publication1
    Mutagenesisi287N → A: Impairs enzyme activity. 1 Publication1

    Organism-specific databases

    DisGeNETi23210.
    OpenTargetsiENSG00000070495.
    PharmGKBiPA162392513.

    Polymorphism and mutation databases

    BioMutaiJMJD6.
    DMDMi67461014.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001293691 – 403Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6Add BLAST403

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei38PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ6NYC1.
    MaxQBiQ6NYC1.
    PaxDbiQ6NYC1.
    PeptideAtlasiQ6NYC1.
    PRIDEiQ6NYC1.

    PTM databases

    iPTMnetiQ6NYC1.
    PhosphoSitePlusiQ6NYC1.

    Expressioni

    Tissue specificityi

    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 Publications

    Inductioni

    Up-regulated upon cytokine treatment, but not upon TNF treatment.1 Publication

    Gene expression databases

    BgeeiENSG00000070495.
    CleanExiHS_JMJD6.
    ExpressionAtlasiQ6NYC1. baseline and differential.
    GenevisibleiQ6NYC1. HS.

    Organism-specific databases

    HPAiCAB004548.
    HPA059156.

    Interactioni

    Subunit structurei

    Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65. Interacts with BRD4. Interacts with LIAT1 (By similarity).By similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-8464037,EBI-8464037
    BRD4O6088510EBI-8464037,EBI-723869
    CDK9P507505EBI-8464037,EBI-1383449
    FRMD6Q96NE93EBI-8464037,EBI-741729
    NAA50Q9GZZ13EBI-8464037,EBI-1052523
    PRPF38AQ8NAV12EBI-8464037,EBI-715374
    U2AF1Q010812EBI-8464037,EBI-632461
    ZCCHC17Q9NP642EBI-8464037,EBI-746345

    GO - Molecular functioni

    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    BioGridi116817. 129 interactors.
    DIPiDIP-60686N.
    IntActiQ6NYC1. 31 interactors.
    MINTiMINT-3086431.
    STRINGi9606.ENSP00000394085.

    Structurei

    Secondary structure

    1403
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi3 – 16Combined sources14
    Helixi23 – 27Combined sources5
    Helixi31 – 34Combined sources4
    Helixi39 – 41Combined sources3
    Beta strandi48 – 50Combined sources3
    Helixi51 – 53Combined sources3
    Helixi56 – 62Combined sources7
    Turni63 – 67Combined sources5
    Beta strandi70 – 74Combined sources5
    Turni75 – 78Combined sources4
    Helixi81 – 84Combined sources4
    Helixi87 – 93Combined sources7
    Beta strandi98 – 103Combined sources6
    Beta strandi109 – 113Combined sources5
    Helixi114 – 123Combined sources10
    Beta strandi132 – 135Combined sources4
    Helixi137 – 139Combined sources3
    Helixi143 – 149Combined sources7
    Helixi154 – 156Combined sources3
    Helixi160 – 164Combined sources5
    Turni166 – 168Combined sources3
    Beta strandi173 – 178Combined sources6
    Beta strandi183 – 187Combined sources5
    Helixi190 – 192Combined sources3
    Beta strandi194 – 202Combined sources9
    Beta strandi204 – 209Combined sources6
    Helixi215 – 218Combined sources4
    Helixi222 – 225Combined sources4
    Helixi226 – 228Combined sources3
    Helixi232 – 238Combined sources7
    Helixi240 – 244Combined sources5
    Helixi250 – 252Combined sources3
    Beta strandi255 – 259Combined sources5
    Beta strandi264 – 267Combined sources4
    Beta strandi272 – 279Combined sources8
    Beta strandi281 – 288Combined sources8
    Turni291 – 293Combined sources3
    Helixi294 – 304Combined sources11
    Helixi306 – 319Combined sources14
    Helixi321 – 333Combined sources13

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3K2OX-ray1.75A/B2-335[»]
    3LD8X-ray2.70A1-334[»]
    3LDBX-ray2.70A1-334[»]
    ProteinModelPortaliQ6NYC1.
    SMRiQ6NYC1.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ6NYC1.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini141 – 305JmjCPROSITE-ProRule annotationAdd BLAST165

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi6 – 10Nuclear localization signal 11 Publication5
    Motifi91 – 95Nuclear localization signal 21 Publication5
    Motifi141 – 145Nuclear localization signal 31 Publication5
    Motifi167 – 170Nuclear localization signal 41 Publication4
    Motifi373 – 378Nuclear localization signal 51 Publication6

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi340 – 365Ser-richAdd BLAST26

    Domaini

    The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus.

    Sequence similaritiesi

    Belongs to the JMJD6 family.Curated
    Contains 1 JmjC domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG2130. Eukaryota.
    ENOG410XQCR. LUCA.
    GeneTreeiENSGT00530000063579.
    HOGENOMiHOG000265824.
    HOVERGENiHBG054774.
    InParanoidiQ6NYC1.
    KOiK11323.
    OrthoDBiEOG091G0AJ6.
    PhylomeDBiQ6NYC1.
    TreeFamiTF314988.

    Family and domain databases

    InterProiIPR003347. JmjC_dom.
    [Graphical view]
    PfamiPF02373. JmjC. 1 hit.
    [Graphical view]
    SMARTiSM00558. JmjC. 1 hit.
    [Graphical view]
    PROSITEiPS51184. JMJC. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q6NYC1-1) [UniParc]FASTAAdd to basket
    Also known as: Alpha

    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.

    « Hide

            10         20         30         40         50
    MNHKSKKRIR EAKRSARPEL KDSLDWTRHN YYESFSLSPA AVADNVERAD
    60 70 80 90 100
    ALQLSVEEFV ERYERPYKPV VLLNAQEGWS AQEKWTLERL KRKYRNQKFK
    110 120 130 140 150
    CGEDNDGYSV KMKMKYYIEY MESTRDDSPL YIFDSSYGEH PKRRKLLEDY
    160 170 180 190 200
    KVPKFFTDDL FQYAGEKRRP PYRWFVMGPP RSGTGIHIDP LGTSAWNALV
    210 220 230 240 250
    QGHKRWCLFP TSTPRELIKV TRDEGGNQQD EAITWFNVIY PRTQLPTWPP
    260 270 280 290 300
    EFKPLEILQK PGETVFVPGG WWHVVLNLDT TIAITQNFAS STNFPVVWHK
    310 320 330 340 350
    TVRGRPKLSR KWYRILKQEH PELAVLADSV DLQESTGIAS DSSSDSSSSS
    360 370 380 390 400
    SSSSSDSDSE CESGSEGDGT VHRRKKRRTC SMVGNGDTTS QDDCVSKERS

    SSR
    Length:403
    Mass (Da):46,462
    Last modified:July 5, 2004 - v1
    Checksum:i9C9AADA98B24B035
    GO
    Isoform 2 (identifier: Q6NYC1-2) [UniParc]FASTAAdd to basket
    Also known as: Beta

    The sequence of this isoform differs from the canonical sequence as follows:
         361-402: Missing.
         403-403: R → RIRDTCGGRAHP

    Show »
    Length:372
    Mass (Da):43,109
    Checksum:i14154B874F1983DF
    GO
    Isoform 3 (identifier: Q6NYC1-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         403-403: R → RIRDTCGGRAHP

    Show »
    Length:414
    Mass (Da):47,626
    Checksum:iCD586580857C6C46
    GO

    Sequence cautioni

    The sequence AAH47003 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence BAA25511 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti136S → G in BAG51050 (PubMed:14702039).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_014022361 – 402Missing in isoform 2. 1 PublicationAdd BLAST42
    Alternative sequenceiVSP_014023403R → RIRDTCGGRAHP in isoform 2 and isoform 3. 3 Publications1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB073711 mRNA. Translation: BAC16755.1.
    AB011157 mRNA. Translation: BAA25511.1. Different initiation.
    AK021780 mRNA. Translation: BAG51050.1.
    AK294816 mRNA. Translation: BAG57932.1.
    AC005837 Genomic DNA. No translation available.
    CH471099 Genomic DNA. Translation: EAW89434.1.
    BC047003 mRNA. Translation: AAH47003.1. Different initiation.
    BC066654 mRNA. Translation: AAH66654.1.
    CCDSiCCDS42383.1. [Q6NYC1-3]
    CCDS42384.1. [Q6NYC1-1]
    RefSeqiNP_001074930.1. NM_001081461.1. [Q6NYC1-3]
    NP_055982.2. NM_015167.2. [Q6NYC1-1]
    UniGeneiHs.514505.

    Genome annotation databases

    EnsembliENST00000397625; ENSP00000380750; ENSG00000070495. [Q6NYC1-1]
    ENST00000445478; ENSP00000394085; ENSG00000070495. [Q6NYC1-3]
    GeneIDi23210.
    KEGGihsa:23210.
    UCSCiuc002jsn.2. human. [Q6NYC1-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB073711 mRNA. Translation: BAC16755.1.
    AB011157 mRNA. Translation: BAA25511.1. Different initiation.
    AK021780 mRNA. Translation: BAG51050.1.
    AK294816 mRNA. Translation: BAG57932.1.
    AC005837 Genomic DNA. No translation available.
    CH471099 Genomic DNA. Translation: EAW89434.1.
    BC047003 mRNA. Translation: AAH47003.1. Different initiation.
    BC066654 mRNA. Translation: AAH66654.1.
    CCDSiCCDS42383.1. [Q6NYC1-3]
    CCDS42384.1. [Q6NYC1-1]
    RefSeqiNP_001074930.1. NM_001081461.1. [Q6NYC1-3]
    NP_055982.2. NM_015167.2. [Q6NYC1-1]
    UniGeneiHs.514505.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3K2OX-ray1.75A/B2-335[»]
    3LD8X-ray2.70A1-334[»]
    3LDBX-ray2.70A1-334[»]
    ProteinModelPortaliQ6NYC1.
    SMRiQ6NYC1.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116817. 129 interactors.
    DIPiDIP-60686N.
    IntActiQ6NYC1. 31 interactors.
    MINTiMINT-3086431.
    STRINGi9606.ENSP00000394085.

    PTM databases

    iPTMnetiQ6NYC1.
    PhosphoSitePlusiQ6NYC1.

    Polymorphism and mutation databases

    BioMutaiJMJD6.
    DMDMi67461014.

    Proteomic databases

    EPDiQ6NYC1.
    MaxQBiQ6NYC1.
    PaxDbiQ6NYC1.
    PeptideAtlasiQ6NYC1.
    PRIDEiQ6NYC1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000397625; ENSP00000380750; ENSG00000070495. [Q6NYC1-1]
    ENST00000445478; ENSP00000394085; ENSG00000070495. [Q6NYC1-3]
    GeneIDi23210.
    KEGGihsa:23210.
    UCSCiuc002jsn.2. human. [Q6NYC1-1]

    Organism-specific databases

    CTDi23210.
    DisGeNETi23210.
    GeneCardsiJMJD6.
    HGNCiHGNC:19355. JMJD6.
    HPAiCAB004548.
    HPA059156.
    MIMi604914. gene.
    neXtProtiNX_Q6NYC1.
    OpenTargetsiENSG00000070495.
    PharmGKBiPA162392513.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2130. Eukaryota.
    ENOG410XQCR. LUCA.
    GeneTreeiENSGT00530000063579.
    HOGENOMiHOG000265824.
    HOVERGENiHBG054774.
    InParanoidiQ6NYC1.
    KOiK11323.
    OrthoDBiEOG091G0AJ6.
    PhylomeDBiQ6NYC1.
    TreeFamiTF314988.

    Enzyme and pathway databases

    BioCyciZFISH:HS12211-MONOMER.
    BRENDAi1.14.11.4. 2681.
    ReactomeiR-HSA-3214842. HDMs demethylate histones.

    Miscellaneous databases

    EvolutionaryTraceiQ6NYC1.
    GeneWikiiJMJD6.
    GenomeRNAii23210.
    PROiQ6NYC1.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000070495.
    CleanExiHS_JMJD6.
    ExpressionAtlasiQ6NYC1. baseline and differential.
    GenevisibleiQ6NYC1. HS.

    Family and domain databases

    InterProiIPR003347. JmjC_dom.
    [Graphical view]
    PfamiPF02373. JmjC. 1 hit.
    [Graphical view]
    SMARTiSM00558. JmjC. 1 hit.
    [Graphical view]
    PROSITEiPS51184. JMJC. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiJMJD6_HUMAN
    AccessioniPrimary (citable) accession number: Q6NYC1
    Secondary accession number(s): B3KMN8
    , B4DGX1, Q86VY0, Q8IUM5, Q9Y4E2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: July 5, 2004
    Last modified: November 2, 2016
    This is version 127 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    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. Phosphatidylserine receptor probably participates in apoptotic cell phagocytosis. This protein was identified using phage display expressing mAb 217, an antibody that specifically recognizes phosphatidylserine receptor. However, its nuclear localization and the fact that mAb 217 antibody still recognizes the phosphatidylserine receptor in mice lacking JMJD6, strongly suggest that it does not constitute the receptor for phosphatidylserine and is not involved in apoptotic cell removal.Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.