Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7YJFO)

DTT Name SET and MYND domain-containing protein 2 (SMYD2)
Synonyms Nlysine methyltransferase SMYD2; N-lysine methyltransferase SMYD2; Lysine Nmethyltransferase 3C; Lysine N-methyltransferase 3C; KMT3C; Histone methyltransferase SMYD2; HSKMB; HSKM-B
Gene Name SMYD2
DTT Type
Preclinical target
 [1]
BioChemical Class
Methyltransferase
UniProt ID
SMYD2_HUMAN
TTD ID
T15797
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.-
Sequence
MRAEGLGGLERFCSPGKGRGLRALQPFQVGDLLFSCPAYAYVLTVNERGNHCEYCFTRKE
GLSKCGRCKQAFYCNVECQKEDWPMHKLECSPMVVFGENWNPSETVRLTARILAKQKIHP
ERTPSEKLLAVKEFESHLDKLDNEKKDLIQSDIAALHHFYSKHLGFPDNDSLVVLFAQVN
CNGFTIEDEELSHLGSAIFPDVALMNHSCCPNVIVTYKGTLAEVRAVQEIKPGEEVFTSY
IDLLYPTEDRNDRLRDSYFFTCECQECTTKDKDKAKVEIRKLSDPPKAEAIRDMVRYARN
VIEEFRRAKHYKSPSELLEICELSQEKMSSVFEDSNVYMLHMMYQAMGVCLYMQDWEGAL
QYGQKIIKPYSKHYPLYSLNVASMWLKLGRLYMGLEHKAAGEKALKKAIAIMEVAHGKDH
PYISEIKQEIESH
Function
Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'. Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1.
KEGG Pathway
Lysine degradation (hsa00310 )
Metabolic pathways (hsa01100 )
Reactome Pathway
PKMTs methylate histone lysines (R-HSA-3214841 )
BioCyc Pathway
MetaCyc:ENSG00000143499-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
6 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
A-893 DM8XHJG Lung cancer 2C25.0 Preclinical [2]
AZ505 DMKQ20J Solid tumour/cancer 2A00-2F9Z Preclinical [3]
BAY 598 DMWH19X Discovery agent N.A. Preclinical [4]
EPZ032597 DMHU742 Solid tumour/cancer 2A00-2F9Z Preclinical [5]
EPZ033294 DMDO6NZ Solid tumour/cancer 2A00-2F9Z Preclinical [5]
LLY-507 DMNOE1M Solid tumour/cancer 2A00-2F9Z Preclinical [1]
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⏷ Show the Full List of 6 Preclinical Drug(s)

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2714).
2 Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2. ACS Med Chem Lett. 2015 Apr 29;6(6):695-700.
3 Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73.
4 Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2. J Med Chem. 2016 May 26;59(10):4578-600.
5 Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286.