Target Information
| Target General Information | Top | |||||
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| Target ID |
T18784
(Former ID: TTDI03365)
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| Target Name |
Lysine-specific demethylase 7A (KDM7A)
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| Synonyms |
Lysine-specific demethylase 7; KIAA1718; KDM7; JmjC domain-containing histone demethylation protein 1D; JHDM1D
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| Gene Name |
KDM7A
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
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.
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| UniProt ID | ||||||
| EC Number |
EC 1.14.11.-
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| Sequence |
MAGAAAAVAAGAAAGAAAAAVSVAAPGRASAPPPPPPVYCVCRQPYDVNRFMIECDICKD
WFHGSCVGVEEHHAVDIDLYHCPNCAVLHGSSLMKKRRNWHRHDYTEIDDGSKPVQAGTR TFIKELRSRVFPSADEIIIKMHGSQLTQRYLEKHGFDVPIMVPKLDDLGLRLPSPTFSVM DVERYVGGDKVIDVIDVARQADSKMTLHNYVKYFMNPNRPKVLNVISLEFSDTKMSELVE VPDIAKKLSWVENYWPDDSVFPKPFVQKYCLMGVQDSYTDFHIDFGGTSVWYHVLWGEKI FYLIKPTDENLARYESWSSSVTQSEVFFGDKVDKCYKCVVKQGHTLFVPTGWIHAVLTSQ DCMAFGGNFLHNLNIGMQLRCYEMEKRLKTPDLFKFPFFEAICWFVAKNLLETLKELRED GFQPQTYLVQGVKALHTALKLWMKKELVSEHAFEIPDNVRPGHLIKELSKVIRAIEEENG KPVKSQGIPIVCPVSRSSNEATSPYHSRRKMRKLRDHNVRTPSNLDILELHTREVLKRLE MCPWEEDILSSKLNGKFNKHLQPSSTVPEWRAKDNDLRLLLTNGRIIKDERQPFADQSLY TADSENEEDKRRTKKAKMKIEESSGVEGVEHEESQKPLNGFFTRVKSELRSRSSGYSDIS ESEDSGPECTALKSIFTTEESESSGDEKKQEITSNFKEESNVMRNFLQKSQKPSRSEIPI KRECPTSTSTEEEAIQGMLSMAGLHYSTCLQRQIQSTDCSGERNSLQDPSSCHGSNHEVR QLYRYDKPVECGYHVKTEDPDLRTSSWIKQFDTSRFHPQDLSRSQKCIRKEGSSEISQRV QSRNYVDSSGSSLQNGKYMQNSNLTSGACQISNGSLSPERPVGETSFSVPLHPTKRPASN PPPISNQATKGKRPKKGMATAKQRLGKILKLNRNGHARFFV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 2-(carboxymethylamino)-2-oxoacetic acid | Ligand Info | |||||
| Structure Description | Structure of KIAA1718 Jumonji domain in complex with N-oxalylglycine | PDB:3KVB | ||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | No | [2] |
| PDB Sequence |
PVQAGTRTFI
123 KELRSRVFPS133 ADEIIIKMHG143 SQLTQRYLEK153 HGFDVPIMVP163 KLDDLGLRLP 173 SPTFSVMDVE183 RYVGGDKVID193 VIDVARQADS203 KMTLHNYVKY213 FMNPNRPKVL 223 NVISLEFSDT233 KMSELVEVPD243 IAKKLSWVEN253 YWPDDSVFPK263 PFVQKYCLMG 273 VQDSYTDFHI283 DFGGTSVWYH293 VLWGEKIFYL303 IKPTDENLAR313 YESWSSSVTQ 323 SEVFFGDKVD333 KCYKCVVKQG343 HTLFVPTGWI353 HAVLTSQDCM363 AFGGNFLHNL 373 NIGMQLRCYE383 MEKRLKTPDL393 FKFPFFEAIC403 WFVAKNLLET413 LKELREDGFQ 423 PQTYLVQGVK433 ALHTALKLWM443 KKELVSEHAF453 EIPDNVRPGH463 LIKELSKVIR 473 AIEEEN
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| Ligand Name: Alpha-ketoglutaric acid | Ligand Info | |||||
| Structure Description | E67-2 selectively inhibits KIAA1718, a human histone H3 lysine 9 Jumonji demethylase | PDB:3U78 | ||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | No | [3] |
| PDB Sequence |
PVQAGTRTFI
123 KELRSRVFPS133 ADEIIIKMHG143 SQLTQRYLEK153 HGFDVPIMVP163 KLDDLGLRLP 173 SPTFSVMDVE183 RYVGGDKVID193 VIDVARQADS203 KMTLHNYVKY213 FMNPNRPKVL 223 NVISLEFSDT233 KMSELVEVPD243 IAKKLSWVEN253 YWPDDSVFPK263 PFVQKYCLMG 273 VQDSYTDFHI283 DFGGTSVWYH293 VLWGEKIFYL303 IKPTDENLAR313 YESWSSSVTQ 323 SEVFFGDKVD333 KCYKCVVKQG343 HTLFVPTGWI353 HAVLTSQDCM363 AFGGNFLHNL 373 NIGMQLRCYE383 MEKRLKTPDL393 FKFPFFEAIC403 WFVAKNLLET413 LKELREDGFQ 423 PQTYLVQGVK433 ALHTALKLWM443 KKELVSEHAF453 EIPDNVRPGH463 LIKELSKVIR 473 AIEEEN
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases. J Med Chem. 2012 Jul 26;55(14):6639-43. | |||||
| REF 2 | Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases. Nat Struct Mol Biol. 2010 Jan;17(1):38-43. | |||||
| REF 3 | An analog of BIX-01294 selectively inhibits a family of histone H3 lysine 9 Jumonji demethylases. J Mol Biol. 2012 Feb 24;416(3):319-27. | |||||
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