metA Resolved · high auto-curated

H37Rv Rv3341 · MTBC0 mtbc0_003553 · 379 aa · 3753474–3754613 (+) · RefSeq NP_217858.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)homoserine O-acetyltransferase
MTBC0 PGAP re-annotationhomoserine O-acetyltransferase
Revised (this work)Homoserine O-acetyltransferase. Pfam: Abhydrolase_1 (PF00561.27).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WJY9 SwissProt · reviewed · Evidence at protein level
UniProt nameHomoserine O-acetyltransferase
EC (curated) EC 2.3.1.31
Curated functionTransfers an acetyl group from acetyl-CoA to L-homoserine, forming acetyl-L-homoserine.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namemetXA
eggNOG descriptionTransfers an acetyl group from acetyl-CoA to L- homoserine, forming acetyl-L-homoserine
Orthologous groupCOG2021
EC number EC 2.3.1.31
KEGG orthology K00641
KEGG pathways map00270, map01100, map01130
Gene Ontology (49) GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0004414, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006555, GO:0006790 +37 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 0.548 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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)

PfamAccessioni-EvalueResiduesDescription
Abhydrolase_1PF00561.27 4.6e-1952–356 alpha/beta hydrolase fold

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: metC (O-acetylhomoserine sulfhydrylase), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3340 metC O-acetylhomoserine sulfhydrylase 999 999 ctx neighborhood:872 cooccurence:499 coexpression:817 database:900 textmining:648
Rv3342 methyltransferase 984 984 ctx neighborhood:881 coexpression:868
Rv1294 thrA homoserine dehydrogenase 951 944 database:900
Rv0391 metZ O-succinylhomoserine sulfhydrylase 957 931 database:900 textmining:409
Rv1079 metB cystathionine gamma-synthase 952 922 database:900 textmining:419
Rv1559 ilvA threonine dehydratase IlvA 845 829 database:800
Rv1077 cbs cystathionine beta-synthase 836 811 database:800
Rv1093 glyA1 serine hydroxymethyltransferase 824 803 database:800
Rv3042c serB2 phosphoserine phosphatase SerB 811 803 database:800
Rv0070c glyA2 serine hydroxymethyltransferase 823 801 database:800
Rv1612 trpB tryptophan synthase subunit beta 810 801 database:800
Rv1613 trpA tryptophan synthase subunit alpha 801 801 database:800
Rv0069c sdaA L-serine dehydratase 800 801 database:800
Rv0436c pssA CDP-diacylglycerol--serine O-phosphatidyltransferase 800 800 database:800
Rv2124c metH methionine synthase 818 651 coexpression:456 textmining:501

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: homoserine O-acetyltransferase
  • MTBC0 PGAP product: homoserine O-acetyltransferase
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=5e-19)
  • (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_217858.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27)
  • 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 COG2021
  • Curated reference: UniProt P9WJY9 (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 — 34 functional partner(s); context anchor metC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003553|Rv3341|metA
MTISDVPTQTLPAEGEIGLIDVGSLQLESGAVIDDVCIAVQRWGKLSPARDNVVVVLHALTGDSHITGPAGPGHPTPGWWDGVAGPGAPIDTTRWCAVATNVLGGCRGSTGPSSLARDGKPWGSRFPLISIRDQVQADVAALAALGITEVAAVVGGSMGGARALEWVVGYPDRVRAGLLLAVGARATADQIGTQTTQIAAIKADPDWQSGDYHETGRAPDAGLRLARRFAHLTYRGEIELDTRFANHNQGNEDPTAGGRYAVQSYLEHQGDKLLSRFDAGSYVILTEALNSHDVGRGRGGVSAALRACPVPVVVGGITSDRLYPLRLQQELADLLPGCAGLRVVESVYGHDGFLVETEAVGELIRQTLGLADREGACRR