fcoT Resolved · high auto-curated

H37Rv Rv0098 · MTBC0 mtbc0_000107 · 183 aa · 107763–108314 (+) · RefSeq NP_214612.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty acyl CoA thioesterase FcoT
MTBC0 PGAP re-annotationfatty acyl CoA thioesterase FcoT
Revised (this work)Fatty acyl CoA thioesterase FcoT. Pfam: FcoT (PF10862.15).

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

Curated reference (UniProt)

UniProt P9WM67 SwissProt · reviewed · Evidence at protein level
UniProt name(2E)-enoyl-[ACP] glycyltransferase
EC (curated) EC 3.1.2.-, EC 3.1.2.2, EC 4.3.2.11
Curated functionInvolved in the biosynthesis of a unique class of isonitrile lipopeptides (INLPs) that seem to function as virulence factors in M.tuberculosis and to play a role in metal acquisition. Catalyzes a Michael addition of glycine to the beta-position of an alpha,beta-unsaturated fatty acyl-[ACP], producing a (3R)-3-[(carboxymethyl)amino]fatty acid. Acts on the (2E)-decenoyl moiety loaded on the acyl-carrier protein (ACP) Rv0100, forming the product (3R)-3-[(carboxymethyl)amino]decanoate released from the ACP (By similarity). Displays thioesterase activity with a preference for long chain fatty acyl .

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namefcoT
eggNOG descriptionFcoT-like thioesterase domain
Orthologous group2CJNX
Gene Ontology (36) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008610 +24 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 0.127 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 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)

PfamAccessioni-EvalueResiduesDescription
FcoTPF10862.15 2.5e-6428–178 FcoT-like thioesterase domain

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

Closest characterised functional partner: Rv0097 (oxidoreductase), high confidence from genomic context alone (score 983 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0097 oxidoreductase 996 983 ctx neighborhood:881 coexpression:860 textmining:807
Rv0101 nrp peptide synthetase Nrp 994 971 ctx neighborhood:800 coexpression:860 textmining:807
Rv0099 fadD10 fatty-acid--CoA ligase FadD10 988 967 ctx neighborhood:776 coexpression:860 textmining:656
Rv0100 hyp hypothetical protein 995 964 ctx neighborhood:776 coexpression:848 textmining:870
Rv0096 PPE1 PPE family protein PPE1 988 964 ctx neighborhood:787 coexpression:839 textmining:696
Rv0095c hyp hypothetical protein 541 527 ctx neighborhood:522
Rv0102 integral membrane protein 539 458 ctx neighborhood:458
Rv2214c ephD oxidoreductase EphD 514 47 textmining:511
Rv1640c lysX bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase 440 44 textmining:439
Rv0052 hyp hypothetical protein 656 42 textmining:656
Rv0109 PE_PGRS1 PE-PGRS family protein PE_PGRS1 435 41 textmining:435

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: fatty acyl CoA thioesterase FcoT
  • MTBC0 PGAP product: fatty acyl CoA thioesterase FcoT
  • Pfam (hmmscan --cut_ga): FcoT PF10862.15 (E=3e-64)
  • (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_214612.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FcoT (PF10862.15)
  • 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 2CJNX
  • Curated reference: UniProt P9WM67 (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 — 11 functional partner(s); context anchor Rv0097
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000107|Rv0098|fcoT
MSHTDLTPCTRVLASSGTVPIAEELLARVLEPYSCKGCRYLIDAQYSATEDSVLAYGNFTIGESAYIRSTGHFNAVELILCFNQLAYSAFAPAVLNEEIRVLRGWSIDDYCQHQLSSMLIRKASSRFRKPLNPQKFSARLLCRDLQVIERTWRYLKVPCVIEFWDENGGAASGEIELAALNIP