Gene name: METTL4

Uniprot entry:

Q8N3J2

Protein names:

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.-)

Protein sequence:

1_MSVVH 6_ QLSAG 11_ WLLDH 16_ LSFIN 21_ KINYQ 26_ LHQHH 31_ EPCCR 36_ KKEFT 41_ TSVHF 46_ ESLQM 51_ DSVSS 56_ SGVCA 61_ AFIAS 66_ DSSTK 71_ PENDD 76_ GGNYE 81_ MFTRK 86_ FVFRP 91_ ELFDV 96_ TKPYI 101_ TPAVH 106_ KECQQ 111_ SNEKE 116_ DLMNG 121_ VKKEI 126_ SISII 131_ GKKRK 136_ RCVVF 141_ NQGEL 146_ DAMEY 151_ HTKIR 156_ ELILD 161_ GSLQL 166_ IQEGL 171_ KSGFL 176_ YPLFE 181_ KQDKG 186_ SKPIT 191_ LPLDA 196_ CSLSE 201_ LCEMA 206_ KHLPS 211_ LNEME 216_ HQTLQ 221_ LVEED 226_ TSVTE 231_ QDLFL 236_ RVVEN 241_ NSSFT 246_ KVITL 251_ MGQKY 256_ LLPPK 261_ SSFLL 266_ SDISC 271_ MQPLL 276_ NYRKT 281_ FDVIV 286_ IDPPW 291_ QNKSV 296_ KRSNR 301_ YSYLS 306_ PLQIQ 311_ QIPIP 316_ KLAAP 321_ NCLLV 326_ TWVTN 331_ RQKHL 336_ RFIKE 341_ ELYPS 346_ WSVEV 351_ VAEWH 356_ WVKIT 361_ NSGEF 366_ VFPLD 371_ SPHKK 376_ PYEGL 381_ ILGRV 386_ QEKTA 391_ LPLRN 396_ ADVNV 401_ LPIPD 406_ HKLIV 411_ SVPCT 416_ LHSHK 421_ PPLAE 426_ VLKDY 431_ IKPDG 436_ EYLEL 441_ FARNL 446_ QPGWT 451_ SWGNE 456_ VLKFQ 461_ HVDYF 466_IAVES

Protein annotations

Protein functions:

1: N(6)-adenine-specific methyltransferase that can methylate both RNAs and DNA (PubMed:31913360, PubMed:32183942). 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 (PubMed:31913360). Internal m6A(m) methylation of snRNAs regulates RNA splicing (PubMed:31913360). 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) (PubMed:32183942). 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 (PubMed:32203414). 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 (PubMed:32183942). 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 (By similarity)