General Information of Drug Therapeutic Target (DTT) (ID: TT3FDAV)

DTT Name DNA [cytosine-5]-methyltransferase 3-like (DNMT3L)
Synonyms DNA (cytosine-5)-methyltransferase 3-like
Gene Name DNMT3L
DTT Type
Patented-recorded target
[1]
UniProt ID
DNM3L_HUMAN
TTD ID
T80487
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAIPALDPEAEPSMDVILVGSSELSSSVSPGTGRDLIAYEVKANQRNIEDICICCGSLQ
VHTQHPLFEGGICAPCKDKFLDALFLYDDDGYQSYCSICCSGETLLICGNPDCTRCYCFE
CVDSLVGPGTSGKVHAMSNWVCYLCLPSSRSGLLQRRRKWRSQLKAFYDRESENPLEMFE
TVPVWRRQPVRVLSLFEDIKKELTSLGFLESGSDPGQLKHVVDVTDTVRKDVEEWGPFDL
VYGATPPLGHTCDRPPSWYLFQFHRLLQYARPKPGSPRPFFWMFVDNLVLNKEDLDVASR
FLEMEPVTIPDVHGGSLQNAVRVWSNIPAIRSRHWALVSEEELSLLAQNKQSSKLAAKWP
TKLVKNCFLPLREYFKYFSTELTSSL
Function
Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain. Acts by accelerating the binding of DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases. Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3. Plays a key role in embryonic stem cells and germ cells. In germ cells, required for the methylation of imprinted loci together with DNMT3A. In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization. Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation. While it promotes DNA methylation of housekeeping genes together with DNMT3A and DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter of bivalent genes. Interacts with the EZH2 component of the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the PRC2/EED-EZH2 complex, leading to maintain low methylation levels at the promoters of bivalent genes. Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression. Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context.
Reactome Pathway
DNA methylation (R-HSA-5334118 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PMID27376512-Compound-Figure2aExample1 DMP59OX N. A. N. A. Patented [1]
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References

1 DNA methyltransferase inhibitors: an updated patent review (2012-2015).Expert Opin Ther Pat. 2016 Sep;26(9):1017-30.