Overview
| Uniprot ID | Q86W50 |
|---|
| Protein Name | RNA N(6)-adenosine-methyltransferase METTL16 |
|---|
| Gene Name | METTL16 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 471 |
EDERSEEKGGVEVLE |
| 5 |
***MALSKSMHARNR |
Function
RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753, PubMed:30197297, PubMed:30197299, PubMed:33428944, PubMed:33930289). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753, PubMed:30197297, PubMed:30197299). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (PubMed:28525753, PubMed:33930289). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200, PubMed:32266935). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311)
Protein Sequence
10
MALSKSMHAR
20
NRYKDKPPDF
30
AYLASKYPDF
40
KQHVQINLNG
50
RVSLNFKDPE
60
AVRALTCTLL
70
REDFGLSIDI
80
PLERLIPTVP
90
LRLNYIHWVE
100
DLIGHQDSDK
110
STLRRGIDIG
120
TGASCIYPLL
130
GATLNGWYFL
140
ATEVDDMCFN
150
YAKKNVEQNN
160
LSDLIKVVKV
170
PQKTLLMDAL
180
KEESEIIYDF
190
CMCNPPFFAN
200
QLEAKGVNSR
210
NPRRPPPSSV
220
NTGGITEIMA
230
EGGELEFVKR
240
IIHDSLQLKK
250
RLRWYSCMLG
260
KKCSLAPLKE
270
ELRIQGVPKV
280
TYTEFCQGRT
290
MRWALAWSFY
300
DDVTVPSPPS
310
KRRKLEKPRK
320
PITFVVLASV
330
MKELSLKASP
340
LRSETAEGIV
350
VVTTWIEKIL
360
TDLKVQHKRV
370
PCGKEEVSLF
380
LTAIENSWIH
390
LRRKKRERVR
400
QLREVPRAPE
410
DVIQALEEKK
420
PTPKESGNSQ
430
ELARGPQERT
440
PCGPALREGE
450
AAAVEGPCPS
460
QESLSQEENP
470
EPTEDERSEE
480
KGGVEVLESC
490
QGSSNGAQDQ
500
EASEQFGSPV
510
AERGKRLPGV
520
AGQYLFKCLI
530
NVKKEVDDAL
540
VEMHWVEGQN
550
RDLMNQLCTY
560
IRNQIFRLVA
VN
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Biological Process |
GO:0120049 |
snRNA (adenine-N6)-methylation |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0052907 |
23S rRNA (adenine(1618)-N(6))-methyltransferase activity |
| Molecular Function |
GO:0001734 |
mRNA m(6)A methyltransferase activity |
| Molecular Function |
GO:0003723 |
RNA binding |
| Molecular Function |
GO:0035613 |
RNA stem-loop binding |
| Molecular Function |
GO:0120048 |
U6 snRNA (adenine-(43)-N(6))-methyltransferase activity |
| Molecular Function |
GO:0030629 |
U6 snRNA 3'-end binding |
| Biological Process |
GO:0006402 |
mRNA catabolic process |
| Biological Process |
GO:0061157 |
mRNA destabilization |
| Biological Process |
GO:0006397 |
mRNA processing |
| Biological Process |
GO:1905869 |
negative regulation of 3'-UTR-mediated mRNA stabilization |
| Biological Process |
GO:0010608 |
post-transcriptional regulation of gene expression |
| Biological Process |
GO:0048024 |
regulation of mRNA splicing, via spliceosome |
| Biological Process |
GO:0070475 |
rRNA base methylation |
| Biological Process |
GO:0006556 |
S-adenosylmethionine biosynthetic process |
Reference
[1] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.