Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOFXD7)

• DTT Name: Euchromatic histone-lysine N-methyltransferase 1 (EHMT1)
• Synonyms: EHMT1
• Gene Name: EHMT1
• DTT Type: Literature-reported target; [1]
• UniProt ID: EHMT1_HUMAN
• TTD ID: T39996
• EC Number: EC 2.1.1.-
• Sequence:
  MAAADAEAVPARGEPQQDCCVKTELLGEETPMAADEGSAEKQAGEAHMAADGETNGSCEN
  SDASSHANAAKHTQDSARVNPQDGTNTLTRIAENGVSERDSEAAKQNHVTADDFVQTSVI
  GSNGYILNKPALQAQPLRTTSTLASSLPGHAAKTLPGGAGKGRTPSAFPQTPAAPPATLG
  EGSADTEDRKLPAPGADVKVHRARKTMPKSVVGLHAASKDPREVREARDHKEPKEEINKN
  ISDFGRQQLLPPFPSLHQSLPQNQCYMATTKSQTACLPFVLAAAVSRKKKRRMGTYSLVP
  KKKTKVLKQRTVIEMFKSITHSTVGSKGEKDLGASSLHVNGESLEMDSDEDDSEELEEDD
  GHGAEQAAAFPTEDSRTSKESMSEADRAQKMDGESEEEQESVDTGEEEEGGDESDLSSES
  SIKKKFLKRKGKTDSPWIKPARKRRRRSRKKPSGALGSESYKSSAGSAEQTAPGDSTGYM
  EVSLDSLDLRVKGILSSQAEGLANGPDVLETDGLQEVPLCSCRMETPKSREITTLANNQC
  MATESVDHELGRCTNSVVKYELMRPSNKAPLLVLCEDHRGRMVKHQCCPGCGYFCTAGNF
  MECQPESSISHRFHKDCASRVNNASYCPHCGEESSKAKEVTIAKADTTSTVTPVPGQEKG
  SALEGRADTTTGSAAGPPLSEDDKLQGAASHVPEGFDPTGPAGLGRPTPGLSQGPGKETL
  ESALIALDSEKPKKLRFHPKQLYFSARQGELQKVLLMLVDGIDPNFKMEHQNKRSPLHAA
  AEAGHVDICHMLVQAGANIDTCSEDQRTPLMEAAENNHLEAVKYLIKAGALVDPKDAEGS
  TCLHLAAKKGHYEVVQYLLSNGQMDVNCQDDGGWTPMIWATEYKHVDLVKLLLSKGSDIN
  IRDNEENICLHWAAFSGCVDIAEILLAAKCDLHAVNIHGDSPLHIAARENRYDCVVLFLS
  RDSDVTLKNKEGETPLQCASLNSQVWSALQMSKALQDSAPDRPSPVERIVSRDIARGYER
  IPIPCVNAVDSEPCPSNYKYVSQNCVTSPMNIDRNITHLQYCVCIDDCSSSNCMCGQLSM
  RCWYDKDGRLLPEFNMAEPPLIFECNHACSCWRNCRNRVVQNGLRARLQLYRTRDMGWGV
  RSLQDIPPGTFVCEYVGELISDSEADVREEDSYLFDLDNKDGEVYCIDARFYGNVSRFIN
  HHCEPNLVPVRVFMAHQDLRFPRIAFFSTRLIEAGEQLGFDYGERFWDIKGKLFSCRCGS
  PKCRHSSAALAQRQASAAQEAQEDGLPDTSSAAAADPL
• Function: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
  Longevity regulating pathway (hsa04211)
• Reactome Pathway:
  PKMTs methylate histone lysines (R-HSA-3214841)
  Regulation of TP53 Activity through Methylation (R-HSA-6804760)
  Transcriptional Regulation by VENTX (R-HSA-8853884)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
• BioCyc Pathway: MetaCyc:HS17627-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-366	DM1H45U	Solid tumour/cancer	2A00-2F9Z	Preclinical	[2]
BIX-01294	DM5CBNY	Breast cancer	2C60-2C65	Preclinical	[3]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
UNC0638	DM4A1KJ	Discovery agent	N.A.	Investigative	[1]
UNC0642	DM7Y1SO	Discovery agent	N.A.	Investigative	[4]

References

• [1] A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol. 2011 Jul 10;7(8):566-74.
• [2] Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett. 2014 Jan 2;5(2):205-9.
• [3] Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007 Feb 9;25(3):473-81.
• [4] Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-42.