Q8TCB7 · METL6_HUMAN
- ProteintRNA N(3)-methylcytidine methyltransferase METTL6
- GeneMETTL6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids284 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
S-adenosyl-L-methionine-dependent methyltransferase that mediates N3-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Ser), including tRNA(Ser)(UGA) and tRNA(Ser)(GCU) (PubMed:32923617, PubMed:34268557, PubMed:34862464, PubMed:34922197).
Interaction with SARS1/SerRS is required for N3-methylcytidine methylation (PubMed:34268557).
Interaction with SARS1/SerRS is required for N3-methylcytidine methylation (PubMed:34268557).
Catalytic activity
- cytidine32 in tRNA(Ser) + S-adenosyl-L-methionine = H+ + N3-methylcytidine32 in tRNA(Ser) + S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.24 μM | tRNA(Ser) | |||||
0.68 μM | S-adenosyl-L-methionine |
kcat is 7200 min-1 for tRNA(Ser) (PubMed:34922197).
kcat is 7100 min-1 for S-adenosyl-L-methionine (PubMed:34922197).
kcat is 7100 min-1 for S-adenosyl-L-methionine (PubMed:34922197).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 45 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 49 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 49 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 61 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 85 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 87 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 87 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 110 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 110 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 136 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 136 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 137 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 137 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 157 | S-adenosyl-L-homocysteine (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 157 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: I |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | enzyme binding | |
Molecular Function | tRNA (cytidine-3-)-methyltransferase activity | |
Biological Process | tRNA methylation | |
Biological Process | tRNA modification |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nametRNA N(3)-methylcytidine methyltransferase METTL6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8TCB7
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 49 | Decreased affinity for S-adenosyl-L-methionine. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 61 | Decreased affinity for S-adenosyl-L-methionine. | ||||
Sequence: H → N | ||||||
Mutagenesis | 85 | Strongly decreased affinity for S-adenosyl-L-methionine. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 93 | Does not affect affinity for S-adenosyl-L-methionine. | ||||
Sequence: C → S | ||||||
Mutagenesis | 110 | Nearly abolished affinity for S-adenosyl-L-methionine. | ||||
Sequence: D → A | ||||||
Mutagenesis | 111 | Decreased affinity for S-adenosyl-L-methionine. | ||||
Sequence: F → L | ||||||
Mutagenesis | 161 | Strongly reduced RNA (cytosine-3-)-methyltransferase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 217 | Strongly reduced RNA (cytosine-3-)-methyltransferase activity. | ||||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 319 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000204454 | 1-284 | UniProt | tRNA N3-methylcytidine methyltransferase METTL6 | |||
Sequence: MASLQRKGLQARILTSEEEEKLKRDQTLVSDFKQQKLEQEAQKNWDLFYKRNSTNFFKDRHWTTREFEELRSCREFEDQKLTMLEAGCGVGNCLFPLLEEDPNIFAYACDFSPRAIEYVKQNPLYDTERCKVFQCDLTKDDLLDHVPPESVDVVMLIFVLSAVHPDKMHLVLQNIYKVLKPGKSVLFRDYGLYDHAMLRFKASSKLGENFYVRQDGTRSYFFTDDFLAQLFMDTGYEEVVNEYVFRETVNKKEGLCVPRVFLQSKFLKPPKNPSPVVLGLDPKS | |||||||
Modified residue (large scale data) | 274 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 284 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Monomer (PubMed:34862464).
Interacts with SARS1/SerRS; interaction is mediated via tRNA(Ser) and is required for N3-methylcytidine methylation (PubMed:28655767, PubMed:34268557).
Interacts with SARS1/SerRS; interaction is mediated via tRNA(Ser) and is required for N3-methylcytidine methylation (PubMed:28655767, PubMed:34268557).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8TCB7 | GPANK1 O95872 | 3 | EBI-17861723, EBI-751540 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q8TCB7-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length284
- Mass (Da)33,251
- Last updated2009-11-24 v2
- Checksum445CAAE4D669B07F
Q8TCB7-2
- Name2
- Differences from canonical
- 178-284: VLKPGKSVLFRDYGLYDHAMLRFKASSKLGENFYVRQDGTRSYFFTDDFLAQLFMDTGYEEVVNEYVFRETVNKKEGLCVPRVFLQSKFLKPPKNPSPVVLGLDPKS → CHGCSSELRQPWDKDDFAVTWDPWSPAIRVLLCHSGWSAVAWTWLTAASTSWAQAVLPPQPLK
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 67 | in Ref. 1; BAB71574 | ||||
Sequence: F → L | ||||||
Alternative sequence | VSP_008480 | 178-284 | in isoform 2 | |||
Sequence: VLKPGKSVLFRDYGLYDHAMLRFKASSKLGENFYVRQDGTRSYFFTDDFLAQLFMDTGYEEVVNEYVFRETVNKKEGLCVPRVFLQSKFLKPPKNPSPVVLGLDPKS → CHGCSSELRQPWDKDDFAVTWDPWSPAIRVLLCHSGWSAVAWTWLTAASTSWAQAVLPPQPLK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK057791 EMBL· GenBank· DDBJ | BAB71574.1 EMBL· GenBank· DDBJ | mRNA | ||
AC027125 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC022400 EMBL· GenBank· DDBJ | AAH22400.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. |