General Information of Drug Therapeutic Target (DTT) (ID: TTJW2UQ)

DTT Name EZH2 Y641N mutant (EZH2 Y641N)
Synonyms
Lysine Nmethyltransferase 6 Y641N mutant; Lysine N-methyltransferase 6 Y641N mutant; KMT6 Y641N mutant; Histonelysine Nmethyltransferase EZH2 Y641N mutant; Histone-lysine N-methyltransferase EZH2 Y641N mutant; EZH2 Y641N mutations; ENX1 Y641N mutant; ENX-1 Y641N mutant
Gene Name EZH2
DTT Type
Patented-recorded target
[1]
UniProt ID
EZH2_HUMAN
TTD ID
T04980
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.1.1.43
Sequence
MGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQEW
KQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQNF
MVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNALGQ
YNDDDDDDDGDDPEEREEKQKDLEDHRDDKESRPPRKFPSDKIFEAISSMFPDKGTAEEL
KEKYKELTEQQLPGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFH
ATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRRGRLPN
NSSRPSTPTINVLESKDTDSDREAGTETGGENNDKEEEEKKDETSSSSEANSRCQTPIKM
KPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKESSIIAPA
PAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCDSSCPCVIAQ
NFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAADHWDSKNVS
CKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDK
YMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIGIFAKRAIQTGE
ELFFDYRYSQADALKYVGIEREMEIP
Function
Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2. Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription. Polycomb group (PcG) protein.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
MicroRNAs in cancer (hsa05206 )
Reactome Pathway
Oxidative Stress Induced Senescence (R-HSA-2559580 )
PKMTs methylate histone lysines (R-HSA-3214841 )
Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472 )
Regulation of PTEN gene transcription (R-HSA-8943724 )
Transcriptional Regulation by E2F6 (R-HSA-8953750 )
HCMV Early Events (R-HSA-9609690 )
Defective pyroptosis (R-HSA-9710421 )
PRC2 methylates histones and DNA (R-HSA-212300 )
BioCyc Pathway
MetaCyc:HS02911-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
5 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PMID28394193-Compound-45 DMZJXPF N. A. N. A. Patented [1]
PMID28394193-Compound-46 DMYMPNA N. A. N. A. Patented [1]
PMID28394193-Compound-55 DM2FPHZ N. A. N. A. Patented [1]
PMID28394193-Compound-56 DMQRFZK N. A. N. A. Patented [1]
PMID28394193-Compound-57 DM4Y3US N. A. N. A. Patented [1]
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References

1 EZH2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jul;27(7):797-813.