Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7H3YM)

• DTT Name: Histone-lysine N-methyltransferase KMT5C (KMT5C)
• Synonyms: Lysine N-methyltransferase 5C; Lysine-specific methyltransferase 5C; Suppressor of variegation 4-20 homolog 2; Su(var)4-20 homolog 2; Suv4-20h2; [histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B; [histone H4]-lysine20 N-methyltransferase KMT5B
• Gene Name: KMT5C
• DTT Type: Preclinical target; [1]
• UniProt ID: KMT5C_HUMAN
• TTD ID: T68490
• EC Number: EC 2.1.1.361
• Sequence:
  MGPDRVTARELCENDDLATSLVLDPYLGFRTHKMNVSPVPPLRRQQHLRSALETFLRQRD
  LEAAYRALTLGGWTARYFQSRGPRQEAALKTHVYRYLRAFLPESGFTILPCTRYSMETNG
  AKIVSTRAWKKNEKLELLVGCIAELREADEGLLRAGENDFSIMYSTRKRSAQLWLGPAAF
  INHDCKPNCKFVPADGNAACVKVLRDIEPGDEVTCFYGEGFFGEKNEHCECHTCERKGEG
  AFRTRPREPALPPRPLDKYQLRETKRRLQQGLDSGSRQGLLGPRACVHPSPLRRDPFCAA
  CQPLRLPACSARPDTSPLWLQWLPQPQPRVRPRKRRRPRPRRAPVLSTHHAARVSLHRWG
  GCGPHCRLRGEALVALGQPPHARWAPQQDWHWARRYGLPYVVRVDLRRLAPAPPATPAPA
  GTPGPILIPKQALAFAPFSPPKRLRLVVSHGSIDLDVGGEEL
• Function: Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5C is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4. May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
• Reactome Pathway: PKMTs methylate histone lysines (R-HSA-3214841)
• BioCyc Pathway: MetaCyc:HS13469-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-196	DMFP316	Discovery agent	N.A.	Preclinical	[1]

References

• [1] The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat Chem Biol. 2017 Mar;13(3):317-324.