Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase |
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| MTBC0 PGAP re-annotation | 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase |
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| Revised (this work) | 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase. Pfam: Meth_synt_1 (PF08267.19), Meth_synt_2 (PF01717.25). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK07
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase |
|---|
| EC (curated) |
EC 2.1.1.14
|
|---|
| Curated function | Catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine resulting in methionine formation. |
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Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
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| Preferred name | metE |
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| eggNOG description | Catalyzes the transfer of a methyl group from 5- methyltetrahydrofolate to homocysteine resulting in methionine formation |
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| Orthologous group | COG0620 |
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| EC number |
EC 2.1.1.14
|
|---|
| KEGG orthology |
K00549
|
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| KEGG pathways |
map00270, map00450, map01100, map01110, map01230
|
|---|
| KEGG modules |
M00017
|
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| Gene Ontology (58) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0003871, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +46 more
|
|---|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are
computed annotations, not manual curation; cross-check against the primary literature
before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS |
0.137 · strong purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
8 synonymous, 3 missense, 0 nonsense, 0 frameshift
|
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pN/pS from segregating SNPs (singletons removed) normalised by possible sites.
Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene).
A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic
variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A
clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a
convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
Meth_synt_1 | PF08267.19 |
2.8e-110 | 12–315 |
Cobalamin-independent synthase, N-terminal domain |
Meth_synt_2 | PF01717.25 |
1.7e-156 | 432–754 |
Cobalamin-independent synthase, Catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv1392 metK |
S-adenosylmethionine synthetase |
981 |
970 |
coexpression:662 database:900 textmining:410 |
Rv2124c metH |
methionine synthase |
996 |
956 |
coexpression:521 database:900 textmining:930 |
Rv3248c sahH |
adenosylhomocysteinase |
958 |
953 |
coexpression:526 database:900 |
Rv1079 metB |
cystathionine gamma-synthase |
977 |
946 |
coexpression:461 database:900 textmining:601 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase |
960 |
945 |
coexpression:452 database:900 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase |
969 |
918 |
database:900 textmining:647 |
Rv1077 cbs |
cystathionine beta-synthase |
928 |
906 |
database:900 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM |
956 |
904 |
database:900 textmining:569 |
Rv2294 |
cystathionine beta-lyase |
907 |
904 |
database:900 |
Rv0075 |
aminotransferase |
907 |
904 |
database:900 |
Rv1007c metS |
methionine--tRNA ligase |
905 |
901 |
database:900 |
Rv1294 thrA |
homoserine dehydrogenase |
883 |
868 |
database:800 |
Rv1559 ilvA |
threonine dehydratase IlvA |
842 |
824 |
database:800 |
Rv1296 thrB |
homoserine kinase |
888 |
809 |
database:800 textmining:441 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase |
854 |
808 |
database:800 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression,
experimental, database, text-mining) into a 0–1000 score. The ctx
badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion,
phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an
unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not
depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with
the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase
- MTBC0 PGAP product: 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase
- Pfam (hmmscan --cut_ga): Meth_synt_1 PF08267.19 (E=3e-110), Meth_synt_2 PF01717.25 (E=2e-156)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024),
An imputed ancestral reference genome for the MTBC,
doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215649.1)
- Domains: Pfam-A via hmmscan --cut_ga — Meth_synt_1 (PF08267.19), Meth_synt_2 (PF01717.25)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0620
- Curated reference: UniProt
P9WK07
(SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of
145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
53 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001216|Rv1133c|metE
MTQPVRRQPFTATITGSPRIGPRRELKRATEGYWAGRTSRSELEAVAATLRRDTWSALAAAGLDSVPVNTFSYYDQMLDTAVLLGALPPRVSPVSDGLDRYFAAARGTDQIAPLEMTKWFDTNYHYLVPEIGPSTTFTLHPGKVLAELKEALGQGIPARPVIIGPITFLLLSKAVDGAGAPIERLEELVPVYSELLSLLADGGAQWVQFDEPALVTDLSPDAPALAEAVYTALCSVSNRPAIYVATYFGDPGAALPALARTPVEAIGVDLVAGADTSVAGVPELAGKTLVAGVVDGRNVWRTDLEAALGTLATLLGSAATVAVSTSCSTLHVPYSLEPETDLDDALRSWLAFGAEKVREVVVLARALRDGHDAVADEIASSRAAIASRKRDPRLHNGQIRARIEAIVASGAHRGNAAQRRASQDARLHLPPLPTTTIGSYPQTSAIRVARAALRAGEIDEAEYVRRMRQEITEVIALQERLGLDVLVHGEPERNDMVQYFAEQLAGFFATQNGWVQSYGSRCVRPPILYGDVSRPRAMTVEWITYAQSLTDKPVKGMLTGPVTILAWSFVRDDQPLADTANQVALAIRDETVDLQSAGIAVIQVDEPALRELLPLRRADQAEYLRWAVGAFRLATSGVSDATQIHTHLCYSEFGEVIGAIADLDADVTSIEAARSHMEVLDDLNAIGFANGVGPGVYDIHSPRVPSAEEMADSLRAALRAVPAERLWVNPDCGLKTRNVDEVTASLHNMVAAAREVRAG
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