METTL16
entrez
79066
canonical
uniprot
Q86W50
canonical
ensembl
ENSG00000127804
resolver
ensp
ENSP00000263092
resolver
genesymbol
METTL16
resolver
genesymbol_syn
METT10D
resolver
hgnc
HGNC:28484
resolver
uniprot
B7Z3X7
resolver
uniprot
D3DTI8
resolver
uniprot
Q86TE5
resolver
uniprot
Q96T16
resolver
uniprot
Q9BVG7
resolver
uniprot_entry
B7Z3X7_HUMAN
resolver
uniprot_entry
MET16_HUMAN
resolver
uniprot_sec
D3DTI8
resolver
uniprot_sec
Q86TE5
resolver
uniprot_sec
Q96T16
resolver
uniprot_sec
Q9BVG7
resolver
activity_regulation
ACTIVITY REGULATION: Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding (PubMed:30197297). Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity (PubMed:30197297). mRNA N6-adenosine-methyltransferase activity is inhibited by zinc (PubMed:33428944). {ECO:0000269|PubMed:30197297, ECO:0000269|PubMed:33428944}.
uniprot
proteins
amino_acid_sequence
MALSKSMHARNRYKDKPPDFAYLASKYPDFKQHVQINLNGRVSLNFKDPEAVRALTCTLLREDFGLSIDIPLERLIPTVPLRLNYIHWVEDLIGHQDSDKSTLRRGIDIGTGASCIYPLLGATLNGWYFLATEVDDMCFNYAKKNVEQNNLSDLIKVVKVPQKTLLMDALKEESEIIYDFCMCNPPFFANQLEAKGVNSRNPRRPPPSSVNTGGITEIMAEGGELEFVKRIIHDSLQLKKRLRWYSCMLGKKCSLAPLKEELRIQGVPKVTYTEFCQGRTMRWALAWSFYDDVTVPSPPSKRRKLEKPRKPITFVVLASVMKELSLKASPLRSETAEGIVVVTTWIEKILTDLKVQHKRVPCGKEEVSLFLTAIENSWIHLRRKKRERVRQLREVPRAPEDVIQALEEKKPTPKESGNSQELARGPQERTPCGPALREGEAAAVEGPCPSQESLSQEENPEPTEDERSEEKGGVEVLESCQGSSNGAQDQEASEQFGSPVAERGKRLPGVAGQYLFKCLINVKKEVDDALVEMHWVEGQNRDLMNQLCTYIRNQIFRLVAVN
uniprot
proteins
ec_number
2.1.1.346
uniprot
proteins
ec_number
2.1.1.348
uniprot
proteins
function
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). {ECO:0000269|PubMed:27872311, ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:29051200, ECO:0000269|PubMed:30197297, ECO:0000269|PubMed:30197299, ECO:0000269|PubMed:32266935, ECO:0000269|PubMed:33428944}.
uniprot
proteins
mass_dalton
63621
uniprot
proteins
mutagenesis
MUTAGEN 5..16; /note="KSMHARNRYKDK->ASMHAANAYADA: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 5; /note="K->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 5; /note="K->E: Reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 10; /note="R->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 10; /note="R->D,E: Reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 12; /note="R->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 14; /note="K->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 16; /note="K->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 26; /note="K->A: Does not affect methyltransferase activity; when associated with A-31."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 31; /note="K->A: Does not affect methyltransferase activity; when associated with A-26."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 39; /note="N->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197297"; MUTAGEN 47; /note="K->E: Reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 82; /note="R->A,E: Abolished methyltransferase activity in vitro."; /evidence="ECO:0000269|PubMed:30197297, ECO:0000269|PubMed:30197299"; MUTAGEN 133; /note="E->A: Abolished methyltransferase activity in vitro."; /evidence="ECO:0000269|PubMed:30197297"; MUTAGEN 163; /note="K->A: Increased methyltransferase activity in vitro."; /evidence="ECO:0000269|PubMed:30197297"; MUTAGEN 167; /note="M->A: Increased methyltransferase activity in vitro."; /evidence="ECO:0000269|PubMed:30197297"; MUTAGEN 184; /note="N->A: Abolished methyltransferase activity in vitro."; /evidence="ECO:0000269|PubMed:30197297"; MUTAGEN 185..186; /note="PP->AA: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:30197299"; MUTAGEN 187; /note="F->G: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:30197299"; MUTAGEN 200..204; /note="RNPRR->ENPEE: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 202..207; /note="PRRPPP->ARRAAA: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 279; /note="R->E: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299"; MUTAGEN 282; /note="R->E: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:30197299
uniprot
proteins
protein_family
METTL16/RlmF family
uniprot
proteins
protein_family
Methyltransferase superfamily
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
27872311
uniprot
proteins
pubmed
28525753
uniprot
proteins
pubmed
29051200
uniprot
proteins
pubmed
29593291
uniprot
proteins
pubmed
30197297
uniprot
proteins
pubmed
30197299
uniprot
proteins
pubmed
31940410
uniprot
proteins
pubmed
32266935
uniprot
proteins
pubmed
33428944
uniprot
proteins
pubmed
33930289
uniprot
proteins
sequence_length
562
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27872311, ECO:0000269|PubMed:31940410}. Cytoplasm {ECO:0000269|PubMed:31940410}.
uniprot
proteins