METTL1
entrez
4234
canonical
uniprot
Q9UBP6
canonical
ensembl
ENSG00000037897
resolver
ensp
ENSP00000257848
resolver
ensp
ENSP00000314441
resolver
ensp
ENSP00000730434
resolver
genesymbol
METTL1
resolver
genesymbol_syn
C12orf1
resolver
hgnc
HGNC:7030
resolver
uniprot
B2RBX1
resolver
uniprot
H7BXF2
resolver
uniprot
Q14105
resolver
uniprot
Q53FS9
resolver
uniprot_entry
TRMB_HUMAN
resolver
uniprot_sec
B2RBX1
resolver
uniprot_sec
H7BXF2
resolver
uniprot_sec
Q14105
resolver
uniprot_sec
Q53FS9
resolver
amino_acid_sequence
MAAETRNVAGAEAPPPQKRYYRQRAHSNPMADHTLRYPVKPEEMDWSELYPEFFAPLTQNQSHDDPKDKKEKRAQAQVEFADIGCGYGGLLVELSPLFPDTLILGLEIRVKVSDYVQDRIRALRAAPAGGFQNIACLRSNAMKHLPNFFYKGQLTKMFFLFPDPHFKRTKHKWRIISPTLLAEYAYVLRVGGLVYTITDVLELHDWMCTHFEEHPLFERVPLEDLSEDPVVGHLGTSTEEGKKVLRNGGKNFPAIFRRIQDPVLQAVTSQTSLPGH
uniprot
proteins
ec_number
2.1.1.-
uniprot
proteins
ec_number
2.1.1.33
uniprot
proteins
function
FUNCTION: Catalytic component of METTL1-WDR4 methyltransferase complex that mediates the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, PubMed:37369656, PubMed:37379838). Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352206, PubMed:34352207, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also acts as a methyltransferase for a subset of internal N(7)-methylguanine in mRNAs (PubMed:31031084, PubMed:37379838). Internal N(7)-methylguanine methylation of mRNAs in response to stress promotes their relocalization to stress granules, thereby suppressing their translation (PubMed:31031084, PubMed:37379838). Also methylates a specific subset of miRNAs, such as let-7 (PubMed:31031083). N(7)-methylguanine methylation of let-7 miRNA promotes let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA) (PubMed:31031083). Acts as a regulator of embryonic stem cell self-renewal and differentiation (By similarity). {ECO:0000255|HAMAP-Rule:MF_03055, ECO:0000269|PubMed:12403464, ECO:0000269|PubMed:31031083, ECO:0000269|PubMed:31031084, ECO:0000269|PubMed:34352206, ECO:0000269|PubMed:34352207, ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656, ECO:0000269|PubMed:37379838}.
uniprot
proteins
mass_dalton
31471
uniprot
proteins
mutagenesis
MUTAGEN 18; /note="K->A: Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 24; /note="R->A: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 27; /note="S->A,S,C,I: Abolished phosphorylation; does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:36599985"; MUTAGEN 27; /note="S->D,E: Mimics phosphorylation; abolished affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985"; MUTAGEN 27; /note="S->K,W: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 29; /note="P->A: Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 40; /note="K->D: Abolished interaction with WDR4; when associated with D-143, D-151 and D-172."; /evidence="ECO:0000269|PubMed:37369656"; MUTAGEN 107..109; /note="EIR->AAA: Abolished RNA methyltransferase activity."; /evidence="ECO:0000269|PubMed:31031083, ECO:0000269|PubMed:37379838"; MUTAGEN 109; /note="R->A: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 111; /note="K->A: Slightly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 118; /note="D->A: Slightly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 143; /note="K->A: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 143; /note="K->D: Abolished interaction with WDR4; when associated with D-40, D-151 and D-172."; /evidence="ECO:0000269|PubMed:37369656"; MUTAGEN 151; /note="K->D: Abolished interaction with WDR4; when associated with D-40, D-143 and D-172."; /evidence="ECO:0000269|PubMed:37369656"; MUTAGEN 160..163; /note="LFPD->AFPA: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:34352206, ECO:0000269|PubMed:36599985"; MUTAGEN 163; /note="D->A: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 165; /note="H->A: Abolished tRNA-binding; when associated with A-167, A-170, A-243 and A-246."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 167; /note="K->A: Abolished methyltransferase activity. Abolished tRNA-binding; when associated with A-165, A-170, A-243 and A-246."; /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985"; MUTAGEN 168; /note="R->A: Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 170; /note="K->A: Abolished tRNA-binding; when associated with A-165, A-167, A-243 and A-246."; /evidence="ECO:0000269|PubMed:36599985"; MUTAGEN 172; /note="K->D: Abolished interaction with WDR4; when associated with D-40, D-143 and D-151."; /evidence="ECO:0000269|PubMed:37369656"; MUTAGEN 173; /note="W->A: Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 199; /note="D->A: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 240; /note="E->A: Abolished methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982"; MUTAGEN 243; /note="K->A: Slightly reduced tRNA-binding. Abolished tRNA-binding; when associated with A-165, A-167, A-170 and A-246. Strongly reduced methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985"; MUTAGEN 246; /note="R->A: Slightly reduced tRNA-binding. Abolished tRNA-binding; when associated with A-165, A-167, A-170 and A-243. Does not affect methyltransferase activity."; /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985
uniprot
proteins
pathway_participation
PATHWAY: tRNA modification; N(7)-methylguanine-tRNA biosynthesis. {ECO:0000269|PubMed:12403464, ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-27 by PKB/AKT1 inactivates its methyltransferase activity via a steric interference mechanism in the active site that locally disrupts the catalytic center (PubMed:15861136, PubMed:36599985). Phosphorylation at Ser-27 does not affect the interaction with WDR4 (PubMed:15861136). {ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:36599985}.
uniprot
proteins
protein_family
Class I-like SAM-binding methyltransferase superfamily
uniprot
proteins
protein_family
TrmB family
uniprot
proteins
pubmed
10329009
uniprot
proteins
pubmed
12403464
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15861136
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26751069
uniprot
proteins
pubmed
31031083
uniprot
proteins
pubmed
31031084
uniprot
proteins
pubmed
34352206
uniprot
proteins
pubmed
34352207
uniprot
proteins
pubmed
34371184
uniprot
proteins
pubmed
36599982
uniprot
proteins
pubmed
36599985
uniprot
proteins
pubmed
37369656
uniprot
proteins
pubmed
37379838
uniprot
proteins
sequence_length
276
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:26751069}.
uniprot
proteins