metC Resolved · high auto-curated
H37Rv Rv3340 · MTBC0 mtbc0_003552 ·
449 aa · 3752113–3753462 (+) ·
RefSeq NP_217857.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | O-acetylhomoserine sulfhydrylase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional o-acetylhomoserine/o-acetylserine sulfhydrylase |
| Revised (this work) | Bifunctional o-acetylhomoserine/o-acetylserine sulfhydrylase. Pfam: Cys_Met_Meta_PP (PF01053.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53390
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable O-acetylhomoserine sulfhydrylase MetC |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | metY |
| eggNOG description | O-acetylhomoserine sulfhydrylase |
| Orthologous group | COG2873 |
| EC number |
EC 2.5.1.49
|
| KEGG orthology |
K01740
|
| KEGG pathways |
map00270, map01100
|
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 | 1.043 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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 |
|---|---|---|---|---|
Cys_Met_Meta_PP | PF01053.27 | 8.0e-133 | 19–433 | Cys/Met metabolism PLP-dependent enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: metA (homoserine O-acetyltransferase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3341 metA |
homoserine O-acetyltransferase | 999 | 999 ctx | neighborhood:872 cooccurence:499 coexpression:817 database:900 textmining:648 |
Rv2124c metH |
methionine synthase | 984 | 940 | database:900 textmining:755 |
Rv1079 metB |
cystathionine gamma-synthase | 949 | 936 | database:900 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 944 | 936 | database:900 |
Rv3342 |
methyltransferase | 925 | 922 ctx | neighborhood:872 coexpression:415 |
Rv1133c metE |
5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase | 969 | 918 | database:900 textmining:647 |
Rv1077 cbs |
cystathionine beta-synthase | 934 | 914 | database:900 |
Rv0075 |
aminotransferase | 918 | 906 | database:900 |
Rv2294 |
cystathionine beta-lyase | 918 | 906 | database:900 |
Rv3248c sahH |
adenosylhomocysteinase | 916 | 901 | database:900 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 913 | 901 | database:900 |
Rv1294 thrA |
homoserine dehydrogenase | 888 | 872 | database:800 |
Rv1559 ilvA |
threonine dehydratase IlvA | 818 | 818 | database:800 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 837 | 812 | database:800 |
Rv3684 |
lyase | 826 | 812 | 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: O-acetylhomoserine sulfhydrylase
- MTBC0 PGAP product: bifunctional o-acetylhomoserine/o-acetylserine sulfhydrylase
- Pfam (hmmscan --cut_ga): Cys_Met_Meta_PP PF01053.27 (E=8e-133)
- (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_217857.1)
- Domains: Pfam-A via hmmscan --cut_ga — Cys_Met_Meta_PP (PF01053.27)
- 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
COG2873 - Curated reference: UniProt O53390 (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 —
42 functional partner(s); context anchor
metA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003552|Rv3340|metC MSADSNSTDADPTAHWSFETKQIHAGQHPDPTTNARALPIYATTSYTFDDTAHAAALFGLEIPGNIYTRIGNPTTDVVEQRIAALEGGVAALFLSSGQAAETFAILNLAGAGDHIVSSPRLYGGTYNLFHYSLAKLGIEVSFVDDPDDLDTWQAAVRPNTKAFFAETISNPQIDLLDTPAVSEVAHRNGVPLIVDNTIATPYLIQPLAQGADIVVHSATKYLGGHGAAIAGVIVDGGNFDWTQGRFPGFTTPDPSYHGVVFAELGPPAFALKARVQLLRDYGSAASPFNAFLVAQGLETLSLRIERHVANAQRVAEFLAARDDVLSVNYAGLPSSPWHERAKRLAPKGTGAVLSFELAGGIEAGKAFVNALKLHSHVANIGDVRSLVIHPASTTHAQLSPAEQLATGVSPGLVRLAVGIEGIDDILADLELGFAAARRFSADPQSVAAF