UniProtKB - Q6ZMT4 (KDM7A_HUMAN)
Protein
Lysine-specific demethylase 7A
Gene
KDM7A
Organism
Homo sapiens (Human)
Status
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
- KM=1.2 µM for histone H3 H3K9Me21 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 279 | SubstrateBy similarity | 1 | |
Metal bindingi | 282 | Iron; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 284 | Iron; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Binding sitei | 299 | SubstrateBy similarity | 1 | |
Metal bindingi | 354 | Iron; catalyticPROSITE-ProRule annotation1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 37 – 88 | PHD-typePROSITE-ProRule annotationAdd BLAST | 52 |
GO - Molecular functioni
- 2-oxoglutarate-dependent dioxygenase activity Source: UniProtKB
- histone demethylase activity Source: GO_Central
- histone demethylase activity (H3-K27 specific) Source: UniProtKB
- histone demethylase activity (H3-K36 specific) Source: UniProtKB
- histone demethylase activity (H3-K9 specific) Source: UniProtKB
- histone demethylase activity (H4-K20 specific) Source: UniProtKB
- iron ion binding Source: UniProtKB
- methylated histone binding Source: UniProtKB
- transcription coregulator activity Source: GO_Central
- zinc ion binding Source: UniProtKB
GO - Biological processi
- histone H3-K27 demethylation Source: UniProtKB
- histone H3-K36 demethylation Source: UniProtKB
- histone H3-K9 demethylation Source: UniProtKB
- histone H4-K20 demethylation Source: UniProtKB
- midbrain development Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: Ensembl
- protein demethylation Source: GO_Central
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Chromatin regulator, Dioxygenase, Oxidoreductase |
Biological process | Neurogenesis, Transcription, Transcription regulation |
Ligand | Iron, Metal-binding, Zinc |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000006459-MONOMER |
PathwayCommonsi | Q6ZMT4 |
Reactomei | R-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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:22224, KDM7A |
neXtProti | NX_Q6ZMT4 |
VEuPathDBi | HostDB:ENSG00000006459.10 |
Subcellular locationi
Nucleus
Nucleus
- nucleolus Source: HPA
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 282 | H → A: Abolishes enzymatic activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 80853 |
OpenTargetsi | ENSG00000006459 |
PharmGKBi | PA162392512 |
Miscellaneous databases
Pharosi | Q6ZMT4, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2163177 |
GuidetoPHARMACOLOGYi | 2686 |
Genetic variation databases
BioMutai | KDM7A |
DMDMi | 90111764 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000226771 | 1 – 941 | Lysine-specific demethylase 7AAdd BLAST | 941 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 604 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q6ZMT4 |
jPOSTi | Q6ZMT4 |
MassIVEi | Q6ZMT4 |
MaxQBi | Q6ZMT4 |
PaxDbi | Q6ZMT4 |
PeptideAtlasi | Q6ZMT4 |
PRIDEi | Q6ZMT4 |
ProteomicsDBi | 67913 [Q6ZMT4-1] 67914 [Q6ZMT4-2] |
PTM databases
iPTMneti | Q6ZMT4 |
PhosphoSitePlusi | Q6ZMT4 |
Expressioni
Gene expression databases
Bgeei | ENSG00000006459, Expressed in layer of synovial tissue and 242 other tissues |
ExpressionAtlasi | Q6ZMT4, baseline and differential |
Genevisiblei | Q6ZMT4, HS |
Organism-specific databases
HPAi | ENSG00000006459, Low tissue specificity |
Interactioni
GO - Molecular functioni
- methylated histone binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 123331, 2 interactors |
IntActi | Q6ZMT4, 2 interactors |
STRINGi | 9606.ENSP00000380692 |
Chemistry databases
BindingDBi | Q6ZMT4 |
Miscellaneous databases
RNActi | Q6ZMT4, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q6ZMT4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q6ZMT4 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 230 – 386 | JmjCPROSITE-ProRule annotationAdd BLAST | 157 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 97 – 114 | LinkerAdd BLAST | 18 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 2 – 31 | Ala-richAdd BLAST | 30 |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 37 – 88 | PHD-typePROSITE-ProRule annotationAdd BLAST | 52 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG1632, Eukaryota KOG1633, Eukaryota |
GeneTreei | ENSGT00940000158039 |
HOGENOMi | CLU_003540_2_1_1 |
InParanoidi | Q6ZMT4 |
OMAi | QIQSTDC |
OrthoDBi | 1384737at2759 |
PhylomeDBi | Q6ZMT4 |
TreeFami | TF106480 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR041070, JHD 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 |
Pfami | View protein in Pfam PF17811, JHD, 1 hit PF02373, JmjC, 1 hit PF00628, PHD, 1 hit |
SMARTi | View protein in SMART SM00558, JmjC, 1 hit SM00249, PHD, 1 hit |
SUPFAMi | SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS51184, JMJC, 1 hit PS01359, ZF_PHD_1, 1 hit PS50016, ZF_PHD_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
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.Curated
Show »Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH9KVD6 | H9KVD6_HUMAN | Lysine-specific demethylase 7A | KDM7A | 404 | Annotation score: |
Sequence cautioni
The sequence BAD18641 differs from that shown. Reason: Frameshift.Curated
The sequence EAL24032 differs from that shown. Reason: Erroneous gene model prediction.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 677 | T → I in CAE46011 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_049653 | 644 | R → S1 PublicationCorresponds to variant dbSNP:rs6950119Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_017458 | 792 – 809 | GYHVK…SSWIK → ETRSHLCCPDWSPTPELK in isoform 2. 1 PublicationAdd BLAST | 18 | |
Alternative sequenceiVSP_017459 | 810 – 941 | Missing in isoform 2. 1 PublicationAdd BLAST | 132 |
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 |
CCDSi | CCDS43658.1 [Q6ZMT4-1] |
RefSeqi | NP_085150.1, NM_030647.1 [Q6ZMT4-1] |
Genome annotation databases
Ensembli | ENST00000397560; ENSP00000380692; ENSG00000006459 [Q6ZMT4-1] |
GeneIDi | 80853 |
KEGGi | hsa:80853 |
UCSCi | uc003vvm.4, human [Q6ZMT4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS43658.1 [Q6ZMT4-1] |
RefSeqi | NP_085150.1, NM_030647.1 [Q6ZMT4-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3KV5 | X-ray | 2.39 | A/D | 1-488 | [»] | |
3KV6 | X-ray | 2.89 | A/D | 1-488 | [»] | |
3KV9 | X-ray | 2.29 | A | 92-488 | [»] | |
3KVA | X-ray | 2.79 | A | 92-488 | [»] | |
3KVB | X-ray | 2.69 | A | 92-488 | [»] | |
3U78 | X-ray | 2.69 | A | 92-488 | [»] | |
SMRi | Q6ZMT4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 123331, 2 interactors |
IntActi | Q6ZMT4, 2 interactors |
STRINGi | 9606.ENSP00000380692 |
Chemistry databases
BindingDBi | Q6ZMT4 |
ChEMBLi | CHEMBL2163177 |
GuidetoPHARMACOLOGYi | 2686 |
PTM databases
iPTMneti | Q6ZMT4 |
PhosphoSitePlusi | Q6ZMT4 |
Genetic variation databases
BioMutai | KDM7A |
DMDMi | 90111764 |
Proteomic databases
EPDi | Q6ZMT4 |
jPOSTi | Q6ZMT4 |
MassIVEi | Q6ZMT4 |
MaxQBi | Q6ZMT4 |
PaxDbi | Q6ZMT4 |
PeptideAtlasi | Q6ZMT4 |
PRIDEi | Q6ZMT4 |
ProteomicsDBi | 67913 [Q6ZMT4-1] 67914 [Q6ZMT4-2] |
Protocols and materials databases
Antibodypediai | 2004, 114 antibodies |
Genome annotation databases
Ensembli | ENST00000397560; ENSP00000380692; ENSG00000006459 [Q6ZMT4-1] |
GeneIDi | 80853 |
KEGGi | hsa:80853 |
UCSCi | uc003vvm.4, human [Q6ZMT4-1] |
Organism-specific databases
CTDi | 80853 |
DisGeNETi | 80853 |
GeneCardsi | KDM7A |
HGNCi | HGNC:22224, KDM7A |
HPAi | ENSG00000006459, Low tissue specificity |
neXtProti | NX_Q6ZMT4 |
OpenTargetsi | ENSG00000006459 |
PharmGKBi | PA162392512 |
VEuPathDBi | HostDB:ENSG00000006459.10 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1632, Eukaryota KOG1633, Eukaryota |
GeneTreei | ENSGT00940000158039 |
HOGENOMi | CLU_003540_2_1_1 |
InParanoidi | Q6ZMT4 |
OMAi | QIQSTDC |
OrthoDBi | 1384737at2759 |
PhylomeDBi | Q6ZMT4 |
TreeFami | TF106480 |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000006459-MONOMER |
PathwayCommonsi | Q6ZMT4 |
Reactomei | R-HSA-3214842, HDMs demethylate histones R-HSA-6802952, Signaling by BRAF and RAF fusions |
Miscellaneous databases
BioGRID-ORCSi | 80853, 4 hits in 994 CRISPR screens |
ChiTaRSi | KDM7A, human |
EvolutionaryTracei | Q6ZMT4 |
GenomeRNAii | 80853 |
Pharosi | Q6ZMT4, Tchem |
PROi | PR:Q6ZMT4 |
RNActi | Q6ZMT4, protein |
Gene expression databases
Bgeei | ENSG00000006459, Expressed in layer of synovial tissue and 242 other tissues |
ExpressionAtlasi | Q6ZMT4, baseline and differential |
Genevisiblei | Q6ZMT4, HS |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR041070, JHD 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 |
Pfami | View protein in Pfam PF17811, JHD, 1 hit PF02373, JmjC, 1 hit PF00628, PHD, 1 hit |
SMARTi | View protein in SMART SM00558, JmjC, 1 hit SM00249, PHD, 1 hit |
SUPFAMi | SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS51184, JMJC, 1 hit PS01359, ZF_PHD_1, 1 hit PS50016, ZF_PHD_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KDM7A_HUMAN | |
Accessioni | Q6ZMT4Primary (citable) accession number: Q6ZMT4 Secondary accession number(s): A4D1S9 Q9C0E5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 7, 2006 |
Last sequence update: | March 7, 2006 | |
Last modified: | April 7, 2021 | |
This is version 142 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families