General Information of Target

Target ID LDTP08833
Target Name N(6)-adenine-specific methyltransferase METTL4 (METTL4)
Gene Name METTL4
Gene ID 64863
Synonyms
N(6)-adenine-specific methyltransferase METTL4; Methyltransferase-like protein 4; N(6)-adenine-specific DNA methyltransferase METTL4; EC 2.1.1.72; snRNA; 2'-O-methyladenosine-N(6)-)-methyltransferase METTL4; EC 2.1.1.-
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSVVHQLSAGWLLDHLSFINKINYQLHQHHEPCCRKKEFTTSVHFESLQMDSVSSSGVCA
AFIASDSSTKPENDDGGNYEMFTRKFVFRPELFDVTKPYITPAVHKECQQSNEKEDLMNG
VKKEISISIIGKKRKRCVVFNQGELDAMEYHTKIRELILDGSLQLIQEGLKSGFLYPLFE
KQDKGSKPITLPLDACSLSELCEMAKHLPSLNEMEHQTLQLVEEDTSVTEQDLFLRVVEN
NSSFTKVITLMGQKYLLPPKSSFLLSDISCMQPLLNYRKTFDVIVIDPPWQNKSVKRSNR
YSYLSPLQIQQIPIPKLAAPNCLLVTWVTNRQKHLRFIKEELYPSWSVEVVAEWHWVKIT
NSGEFVFPLDSPHKKPYEGLILGRVQEKTALPLRNADVNVLPIPDHKLIVSVPCTLHSHK
PPLAEVLKDYIKPDGEYLELFARNLQPGWTSWGNEVLKFQHVDYFIAVESGS
Target Bioclass
Enzyme
Family
MT-A70-like family
Subcellular location
Nucleus
Function
N(6)-adenine-specific methyltransferase that can methylate both RNAs and DNA. Acts as a N(6)-adenine-specific RNA methyltransferase by catalyzing formation of N6,2'-O-dimethyladenosine (m6A(m)) on internal positions of U2 small nuclear RNA (snRNA): methylates the 6th position of adenine residues with a pre-deposited 2'-O-methylation. Internal m6A(m) methylation of snRNAs regulates RNA splicing. Also able to act as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine). The existence of N(6)-methyladenosine (m6A) on DNA is however unclear in mammals, and additional evidences are required to confirm the role of the N(6)-adenine-specific DNA methyltransferase activity of METTL4 in vivo. Acts as a regulator of mitochondrial transcript levels and mitochondrial DNA (mtDNA) copy number by mediating mtDNA N(6)-methylation: m6A on mtDNA reduces transcription by repressing TFAM DNA-binding and bending. N(6)-methyladenosine deposition by METTL4 regulates Polycomb silencing by triggering ubiquitination and degradation of sensor proteins ASXL1 and MPND, leading to inactivation of the PR-DUB complex and subsequent preservation of Polycomb silencing.
Uniprot ID
Q8N3J2
Ensemble ID
ENST00000574538.2
HGNC ID
HGNC:24726

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C33(0.98); C34(0.98)  LDD0078  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0020  ARS-1620 HCC44 C33(0.98); C34(0.98)  LDD0078  [1]
 LDCM0022  KB02 A2780 C108(2.24)  LDD2254  [2]
 LDCM0023  KB03 A2780 C108(2.52)  LDD2671  [2]
 LDCM0024  KB05 OE33 C108(1.76)  LDD3375  [2]

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840