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Protein

Lysine-specific demethylase 7A

Gene

KDM7A

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

Functioni

Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate.3 Publications

Cofactori

Fe2+2 PublicationsNote: Binds 1 Fe2+ ion per subunit.2 Publications

Kineticsi

  1. KM=1.2 µM for histone H3 H3K9Me21 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei279SubstrateBy similarity1
    Metal bindingi282Iron; catalyticPROSITE-ProRule annotation1 Publication1
    Metal bindingi284Iron; catalyticPROSITE-ProRule annotation1 Publication1
    Binding sitei299SubstrateBy similarity1
    Metal bindingi354Iron; catalyticPROSITE-ProRule annotation1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri37 – 88PHD-typePROSITE-ProRule annotationAdd BLAST52

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionChromatin regulator, Dioxygenase, Oxidoreductase
    Biological processNeurogenesis, Transcription, Transcription regulation
    LigandIron, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-HSA-3214842 HDMs demethylate histones
    R-HSA-6802952 Signaling by BRAF and RAF fusions

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lysine-specific demethylase 7A (EC:1.14.11.-)
    Alternative name(s):
    JmjC domain-containing histone demethylation protein 1D
    Lysine-specific demethylase 7
    Gene namesi
    Name:KDM7A
    Synonyms:JHDM1D, KDM7, KIAA1718
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000006459.10
    HGNCiHGNC:22224 KDM7A
    neXtProtiNX_Q6ZMT4

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi282H → A: Abolishes enzymatic activity. 1 Publication1

    Organism-specific databases

    DisGeNETi80853
    OpenTargetsiENSG00000006459
    PharmGKBiPA162392512

    Chemistry databases

    ChEMBLiCHEMBL2163177
    GuidetoPHARMACOLOGYi2686

    Polymorphism and mutation databases

    BioMutaiJHDM1D
    DMDMi90111764

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002267711 – 941Lysine-specific demethylase 7AAdd BLAST941

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei604PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ6ZMT4
    MaxQBiQ6ZMT4
    PaxDbiQ6ZMT4
    PeptideAtlasiQ6ZMT4
    PRIDEiQ6ZMT4
    ProteomicsDBi67913
    67914 [Q6ZMT4-2]

    PTM databases

    iPTMnetiQ6ZMT4
    PhosphoSitePlusiQ6ZMT4

    Expressioni

    Gene expression databases

    BgeeiENSG00000006459 Expressed in 229 organ(s), highest expression level in layer of synovial tissue
    CleanExiHS_JHDM1D
    ExpressionAtlasiQ6ZMT4 baseline and differential
    GenevisibleiQ6ZMT4 HS

    Organism-specific databases

    HPAiHPA012114

    Interactioni

    GO - Molecular functioni

    Protein-protein interaction databases

    IntActiQ6ZMT4, 1 interactor
    STRINGi9606.ENSP00000380692

    Chemistry databases

    BindingDBiQ6ZMT4

    Structurei

    Secondary structure

    1941
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ6ZMT4
    SMRiQ6ZMT4
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ6ZMT4

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini230 – 386JmjCPROSITE-ProRule annotationAdd BLAST157

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni97 – 114LinkerAdd BLAST18

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi2 – 31Ala-richAdd BLAST30

    Domaini

    The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2.1 Publication
    The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2.1 Publication

    Sequence similaritiesi

    Zinc finger

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri37 – 88PHD-typePROSITE-ProRule annotationAdd BLAST52

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiKOG1633 Eukaryota
    ENOG410XQXU LUCA
    GeneTreeiENSGT00550000074396
    HOGENOMiHOG000231232
    HOVERGENiHBG045631
    InParanoidiQ6ZMT4
    KOiK11445
    OMAiWIKQFDT
    OrthoDBiEOG091G09DB
    PhylomeDBiQ6ZMT4
    TreeFamiTF106480

    Family and domain databases

    Gene3Di3.30.40.10, 1 hit
    InterProiView protein in InterPro
    IPR003347 JmjC_dom
    IPR019786 Zinc_finger_PHD-type_CS
    IPR011011 Znf_FYVE_PHD
    IPR001965 Znf_PHD
    IPR019787 Znf_PHD-finger
    IPR013083 Znf_RING/FYVE/PHD
    PfamiView protein in Pfam
    PF02373 JmjC, 1 hit
    PF00628 PHD, 1 hit
    SMARTiView protein in SMART
    SM00558 JmjC, 1 hit
    SM00249 PHD, 1 hit
    SUPFAMiSSF57903 SSF57903, 1 hit
    PROSITEiView protein in PROSITE
    PS51184 JMJC, 1 hit
    PS01359 ZF_PHD_1, 1 hit
    PS50016 ZF_PHD_2, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q6ZMT4-1) [UniParc]FASTAAdd to basket

    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
    MAGAAAAVAA GAAAGAAAAA VSVAAPGRAS APPPPPPVYC VCRQPYDVNR
    60 70 80 90 100
    FMIECDICKD WFHGSCVGVE EHHAVDIDLY HCPNCAVLHG SSLMKKRRNW
    110 120 130 140 150
    HRHDYTEIDD GSKPVQAGTR TFIKELRSRV FPSADEIIIK MHGSQLTQRY
    160 170 180 190 200
    LEKHGFDVPI MVPKLDDLGL RLPSPTFSVM DVERYVGGDK VIDVIDVARQ
    210 220 230 240 250
    ADSKMTLHNY VKYFMNPNRP KVLNVISLEF SDTKMSELVE VPDIAKKLSW
    260 270 280 290 300
    VENYWPDDSV FPKPFVQKYC LMGVQDSYTD FHIDFGGTSV WYHVLWGEKI
    310 320 330 340 350
    FYLIKPTDEN LARYESWSSS VTQSEVFFGD KVDKCYKCVV KQGHTLFVPT
    360 370 380 390 400
    GWIHAVLTSQ DCMAFGGNFL HNLNIGMQLR CYEMEKRLKT PDLFKFPFFE
    410 420 430 440 450
    AICWFVAKNL LETLKELRED GFQPQTYLVQ GVKALHTALK LWMKKELVSE
    460 470 480 490 500
    HAFEIPDNVR PGHLIKELSK VIRAIEEENG KPVKSQGIPI VCPVSRSSNE
    510 520 530 540 550
    ATSPYHSRRK MRKLRDHNVR TPSNLDILEL HTREVLKRLE MCPWEEDILS
    560 570 580 590 600
    SKLNGKFNKH LQPSSTVPEW RAKDNDLRLL LTNGRIIKDE RQPFADQSLY
    610 620 630 640 650
    TADSENEEDK RRTKKAKMKI EESSGVEGVE HEESQKPLNG FFTRVKSELR
    660 670 680 690 700
    SRSSGYSDIS ESEDSGPECT ALKSIFTTEE SESSGDEKKQ EITSNFKEES
    710 720 730 740 750
    NVMRNFLQKS QKPSRSEIPI KRECPTSTST EEEAIQGMLS MAGLHYSTCL
    760 770 780 790 800
    QRQIQSTDCS GERNSLQDPS SCHGSNHEVR QLYRYDKPVE CGYHVKTEDP
    810 820 830 840 850
    DLRTSSWIKQ FDTSRFHPQD LSRSQKCIRK EGSSEISQRV QSRNYVDSSG
    860 870 880 890 900
    SSLQNGKYMQ NSNLTSGACQ ISNGSLSPER PVGETSFSVP LHPTKRPASN
    910 920 930 940
    PPPISNQATK GKRPKKGMAT AKQRLGKILK LNRNGHARFF V
    Length:941
    Mass (Da):106,557
    Last modified:March 7, 2006 - v2
    Checksum:iAB8161020D157F11
    GO
    Isoform 2 (identifier: Q6ZMT4-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         792-809: GYHVKTEDPDLRTSSWIK → ETRSHLCCPDWSPTPELK
         810-941: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
    Show »
    Length:809
    Mass (Da):92,001
    Checksum:i1561533C92AB3466
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H9KVD6H9KVD6_HUMAN
    Lysine-specific demethylase 7A
    KDM7A
    404Annotation score:

    Sequence cautioni

    The sequence BAD18641 differs from that shown. Reason: Frameshift at position 902.Curated
    The sequence EAL24032 differs from that shown. Reason: Erroneous gene model prediction.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti677T → I in CAE46011 (PubMed:17974005).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_049653644R → S1 PublicationCorresponds to variant dbSNP:rs6950119Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_017458792 – 809GYHVK…SSWIK → ETRSHLCCPDWSPTPELK in isoform 2. 1 PublicationAdd BLAST18
    Alternative sequenceiVSP_017459810 – 941Missing in isoform 2. 1 PublicationAdd BLAST132

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK131497 mRNA Translation: BAD18641.1 Frameshift.
    AC004849 Genomic DNA No translation available.
    CH236950 Genomic DNA Translation: EAL24032.1 Sequence problems.
    AB051505 mRNA Translation: BAB21809.1
    BX641017 mRNA Translation: CAE46011.1
    CCDSiCCDS43658.1 [Q6ZMT4-1]
    RefSeqiNP_085150.1, NM_030647.1 [Q6ZMT4-1]
    UniGeneiHs.308710

    Genome annotation databases

    EnsembliENST00000397560; ENSP00000380692; ENSG00000006459 [Q6ZMT4-1]
    GeneIDi80853
    KEGGihsa:80853
    UCSCiuc003vvm.4 human [Q6ZMT4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK131497 mRNA Translation: BAD18641.1 Frameshift.
    AC004849 Genomic DNA No translation available.
    CH236950 Genomic DNA Translation: EAL24032.1 Sequence problems.
    AB051505 mRNA Translation: BAB21809.1
    BX641017 mRNA Translation: CAE46011.1
    CCDSiCCDS43658.1 [Q6ZMT4-1]
    RefSeqiNP_085150.1, NM_030647.1 [Q6ZMT4-1]
    UniGeneiHs.308710

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3KV5X-ray2.39A/D1-488[»]
    3KV6X-ray2.89A/D1-488[»]
    3KV9X-ray2.29A92-488[»]
    3KVAX-ray2.79A92-488[»]
    3KVBX-ray2.69A92-488[»]
    3U78X-ray2.69A92-488[»]
    ProteinModelPortaliQ6ZMT4
    SMRiQ6ZMT4
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ6ZMT4, 1 interactor
    STRINGi9606.ENSP00000380692

    Chemistry databases

    BindingDBiQ6ZMT4
    ChEMBLiCHEMBL2163177
    GuidetoPHARMACOLOGYi2686

    PTM databases

    iPTMnetiQ6ZMT4
    PhosphoSitePlusiQ6ZMT4

    Polymorphism and mutation databases

    BioMutaiJHDM1D
    DMDMi90111764

    Proteomic databases

    EPDiQ6ZMT4
    MaxQBiQ6ZMT4
    PaxDbiQ6ZMT4
    PeptideAtlasiQ6ZMT4
    PRIDEiQ6ZMT4
    ProteomicsDBi67913
    67914 [Q6ZMT4-2]

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000397560; ENSP00000380692; ENSG00000006459 [Q6ZMT4-1]
    GeneIDi80853
    KEGGihsa:80853
    UCSCiuc003vvm.4 human [Q6ZMT4-1]

    Organism-specific databases

    CTDi80853
    DisGeNETi80853
    EuPathDBiHostDB:ENSG00000006459.10
    GeneCardsiKDM7A
    H-InvDBiHIX0007139
    HGNCiHGNC:22224 KDM7A
    HPAiHPA012114
    neXtProtiNX_Q6ZMT4
    OpenTargetsiENSG00000006459
    PharmGKBiPA162392512
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1633 Eukaryota
    ENOG410XQXU LUCA
    GeneTreeiENSGT00550000074396
    HOGENOMiHOG000231232
    HOVERGENiHBG045631
    InParanoidiQ6ZMT4
    KOiK11445
    OMAiWIKQFDT
    OrthoDBiEOG091G09DB
    PhylomeDBiQ6ZMT4
    TreeFamiTF106480

    Enzyme and pathway databases

    ReactomeiR-HSA-3214842 HDMs demethylate histones
    R-HSA-6802952 Signaling by BRAF and RAF fusions

    Miscellaneous databases

    ChiTaRSiKDM7A human
    EvolutionaryTraceiQ6ZMT4
    GenomeRNAii80853
    PROiPR:Q6ZMT4

    Gene expression databases

    BgeeiENSG00000006459 Expressed in 229 organ(s), highest expression level in layer of synovial tissue
    CleanExiHS_JHDM1D
    ExpressionAtlasiQ6ZMT4 baseline and differential
    GenevisibleiQ6ZMT4 HS

    Family and domain databases

    Gene3Di3.30.40.10, 1 hit
    InterProiView protein in InterPro
    IPR003347 JmjC_dom
    IPR019786 Zinc_finger_PHD-type_CS
    IPR011011 Znf_FYVE_PHD
    IPR001965 Znf_PHD
    IPR019787 Znf_PHD-finger
    IPR013083 Znf_RING/FYVE/PHD
    PfamiView protein in Pfam
    PF02373 JmjC, 1 hit
    PF00628 PHD, 1 hit
    SMARTiView protein in SMART
    SM00558 JmjC, 1 hit
    SM00249 PHD, 1 hit
    SUPFAMiSSF57903 SSF57903, 1 hit
    PROSITEiView protein in PROSITE
    PS51184 JMJC, 1 hit
    PS01359 ZF_PHD_1, 1 hit
    PS50016 ZF_PHD_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKDM7A_HUMAN
    AccessioniPrimary (citable) accession number: Q6ZMT4
    Secondary accession number(s): A4D1S9
    , C9JJH9, C9JQU2, Q6MZL8, Q9C0E5
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
    Last sequence update: March 7, 2006
    Last modified: November 7, 2018
    This is version 125 of the entry and version 2 of the sequence. See 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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
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