Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | homocysteine S-methyltransferase MmuM |
|---|
| MTBC0 PGAP re-annotation | homocysteine S-methyltransferase |
|---|
| Revised (this work) | Homocysteine S-methyltransferase. Pfam: S-methyl_trans (PF02574.23). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53185
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | S-methylmethionine:homocysteine methyltransferase |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
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 |
0.376 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 2 missense, 0 nonsense, 0 frameshift
|
|---|
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 |
|---|
S-methyl_trans | PF02574.23 |
9.2e-78 | 9–294 |
Homocysteine S-methyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase |
927 |
918 |
database:900 |
Rv1079 metB |
cystathionine gamma-synthase |
927 |
918 |
database:900 |
Rv2124c metH |
methionine synthase |
957 |
910 |
database:900 textmining:548 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase |
956 |
904 |
database:900 textmining:569 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase |
913 |
901 |
database:900 |
Rv1392 metK |
S-adenosylmethionine synthetase |
923 |
900 |
database:900 |
Rv1077 cbs |
cystathionine beta-synthase |
908 |
900 |
database:900 |
Rv0075 |
aminotransferase |
903 |
900 |
database:900 |
Rv2294 |
cystathionine beta-lyase |
903 |
900 |
database:900 |
Rv3248c sahH |
adenosylhomocysteinase |
902 |
900 |
database:900 |
Rv3684 |
lyase |
835 |
826 |
database:800 |
Rv1294 thrA |
homoserine dehydrogenase |
830 |
809 |
database:800 |
Rv3238c mddA |
integral membrane protein |
807 |
807 |
database:800 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase |
812 |
801 |
database:800 |
Rv1559 ilvA |
threonine dehydratase IlvA |
810 |
800 |
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: homocysteine S-methyltransferase MmuM
- MTBC0 PGAP product: homocysteine S-methyltransferase
- Pfam (hmmscan --cut_ga): S-methyl_trans PF02574.23 (E=9e-78)
- (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_216974.1)
- Domains: Pfam-A via hmmscan --cut_ga — S-methyl_trans (PF02574.23)
- 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
COG2040
- Curated reference: UniProt
O53185
(TrEMBL, unreviewed; 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 —
27 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002617|Rv2458|mmuM
MELVSDSVLISDGGLATELEARGHDLSDPLWSARLLVDAPHAITAVHTAYFRAGAQIATTASYQASFEGFAARGIGHDDATVLLRRSVELAQAARDEVGVGGLSVAASVGPYGAALADGSEYRGCYGLSVAALMKWHLPRLEVLVDAGADMLALETIPDIDEAEALVNLVRRLATPAWLSYTINGTRTRAGQPLTDAFAVAAGVPEIVAVGVNCCAPDDVLPAIAFAVAHTGKPVIVYPNSGEGWDGRRRAWVGPRRFSGSSGQLAREWVAAGARIVGGCCRVRPIDIAEIGRALTTAPPRG
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