Target Information
| Target General Information | Top | |||||
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| Target ID |
T71949
(Former ID: TTDI03360)
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| Target Name |
Lysine-specific demethylase 2A (KDM2A)
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| Synonyms |
FBXL11; FBL7; F-box/LRR-repeat protein 11; F-box protein Lilina; F-box protein FBL7; F-box and leucine-rich repeat protein 11; CXXC8; CXXC-type zinc finger protein 8; [Histone-H3]-lysine-36 demethylase 1A; KIAA1004; JmjC domain-containing histone demethylation protein 1A; JHDM1A
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| Gene Name |
KDM2A
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-ARNTL/BMAL1 heterodimer and RORA in a catalytically-independent manner.
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| UniProt ID | ||||||
| EC Number |
EC 1.14.11.27
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| Sequence |
MEPEEERIRYSQRLRGTMRRRYEDDGISDDEIEGKRTFDLEEKLHTNKYNANFVTFMEGK
DFNVEYIQRGGLRDPLIFKNSDGLGIKMPDPDFTVNDVKMCVGSRRMVDVMDVNTQKGIE MTMAQWTRYYETPEEEREKLYNVISLEFSHTRLENMVQRPSTVDFIDWVDNMWPRHLKES QTESTNAILEMQYPKVQKYCLMSVRGCYTDFHVDFGGTSVWYHIHQGGKVFWLIPPTAHN LELYENWLLSGKQGDIFLGDRVSDCQRIELKQGYTFVIPSGWIHAVYTPTDTLVFGGNFL HSFNIPMQLKIYNIEDRTRVPNKFRYPFYYEMCWYVLERYVYCITNRSHLTKEFQKESLS MDLELNGLESGNGDEEAVDREPRRLSSRRSVLTSPVANGVNLDYDGLGKTCRSLPSLKKT LAGDSSSDCSRGSHNGQVWDPQCAPRKDRQVHLTHFELEGLRCLVDKLESLPLHKKCVPT GIEDEDALIADVKILLEELANSDPKLALTGVPIVQWPKRDKLKFPTRPKVRVPTIPITKP HTMKPAPRLTPVRPAAASPIVSGARRRRVRCRKCKACVQGECGVCHYCRDMKKFGGPGRM KQSCVLRQCLAPRLPHSVTCSLCGEVDQNEETQDFEKKLMECCICNEIVHPGCLQMDGEG LLNEELPNCWECPKCYQEDSSEKAQKRKMEESDEEAVQAKVLRPLRSCDEPLTPPPHSPT SMLQLIHDPVSPRGMVTRSSPGAGPSDHHSASRDERFKRRQLLRLQATERTMVREKENNP SGKKELSEVEKAKIRGSYLTVTLQRPTKELHGTSIVPKLQAITASSANLRHSPRVLVQHC PARTPQRGDEEGLGGEEEEEEEEEEEDDSAEEGGAARLNGRGSWAQDGDESWMQREVWMS VFRYLSRRELCECMRVCKTWYKWCCDKRLWTKIDLSRCKAIVPQALSGIIKRQPVSLDLS WTNISKKQLTWLVNRLPGLKDLLLAGCSWSAVSALSTSSCPLLRTLDLRWAVGIKDPQIR DLLTPPADKPGQDNRSKLRNMTDFRLAGLDITDATLRLIIRHMPLLSRLDLSHCSHLTDQ SSNLLTAVGSSTRYSLTELNMAGCNKLTDQTLIYLRRIANVTLIDLRGCKQITRKACEHF ISDLSINSLYCLSDEKLIQKIS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T74ZEH | |||||
| 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: Alpha-ketoglutaric acid | Ligand Info | |||||
| Structure Description | Crystal structure of hJHDM1A complexed with a-ketoglutarate | PDB:2YU1 | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | Yes | [3] |
| PDB Sequence |
RTFDLEEKLH
45 TNKYNANFVT55 FMEGKDFNVE65 YIQRGGLRDP75 LIFKNSDGLG85 IKMPDPDFTV 95 NDVKMCVGSR105 RMVDVMDVNT115 QKGIEMTMAQ125 WTRYYETPEE135 EREKLYNVIS 145 LEFSHTRLEN155 MVQRPSTVDF165 IDWVDNMWPR175 HLKEMQYPKV196 QKYCLMSVRG 206 CYTDFHVDFG216 GTSVWYHIHQ226 GGKVFWLIPP236 TAHNLELYEN246 WLLSGSQGDI 256 FLGDRVSDCQ266 RIELKQGYTF276 VIPSGWIHAV286 YTPTDTLVFG296 GNFLHSFNIP 306 MQLKIYNIED316 RTRVPNKFRY326 PFYYEMCWYV336 LERYVYCITN346 RSHLTKEFQK 356 ESLSMDLEQV451 HLTHFELEGL461 RCLVDKLESL471 PLHKKCVPTG481 IEDEDALIAD 491 VKILLEELAN501 SDPKLALTGV511 PIVQWP
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| 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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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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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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 2.00E-01 | Radiality | 1.35E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 6.10E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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 | Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases. ACS Chem Biol. 2013 Jul 19;8(7):1488-96. | |||||
| REF 2 | 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 3 | Structural basis for histone demethylation by JHDM1 | |||||
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