umaA Resolved · high auto-curated

H37Rv Rv0469 · MTBC0 - · 286 aa · 559888–560748 (+) · RefSeq YP_177729.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)mycolic acid synthase UmaA
MTBC0 PGAP re-annotation
Revised (this work)Mycolic acid synthase UmaA. Pfam: CMAS (PF02353.27), Methyltransf_23 (PF13489.13), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), Methyltransf_11 (PF08241.19).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt Q6MX39 SwissProt · reviewed · Evidence at protein level
UniProt nameS-adenosylmethionine-dependent methyltransferase UmaA
EC (curated) EC 2.1.1.-
Curated functionMethyltransferase that modifies short-chain fatty acids. In vitro, catalyzes the transfer of the methyl group from S-adenosyl-L-methionine (SAM) to the double bond of phospholipid-linked oleic acid to produce tuberculostearic acid (10-methylstearic-acid or TSA).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameumaA
eggNOG descriptionsynthase
Orthologous groupCOG2230
EC number EC 2.1.1.79
KEGG orthology K00574
Gene Ontology (22) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006629, GO:0008150, GO:0008152, GO:0008168, GO:0008610, GO:0008757, GO:0008825 +10 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 0.625 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (155) · clonal

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
CMASPF02353.27 1.8e-1126–282 Mycolic acid cyclopropane synthetase
Methyltransf_23PF13489.13 9.1e-1059–187 Methyltransferase domain
Methyltransf_25PF13649.13 4.4e-0968–161 Methyltransferase domain
Methyltransf_12PF08242.19 2.2e-0868–162 Methyltransferase domain
Methyltransf_11PF08241.19 5.6e-0668–164 Methyltransferase domain

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

Closest characterised functional partner: fadB2 (3-hydroxybutyryl-CoA dehydrogenase), medium confidence from genomic context alone (score 563 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 649 563 ctx neighborhood:537
Rv0467 icl1 isocitrate lyase 438 397
Rv0447c ufaA1 cyclopropane-fatty-acyl-phospholipid synthase UfaA 459 302
Rv1752 hyp hypothetical protein 528 71 textmining:513
Rv2488c LuxR family transcriptional regulator 420 59 textmining:409
Rv0386 transcriptional regulator 417 54 textmining:409
Rv0472c HTH-type transcriptional regulator 532 53 textmining:527
Rv0824c desA1 acyl-ACP desaturase DesA 443 53 textmining:436
Rv0373c carbon monoxyde dehydrogenase large subunit 414 50 textmining:409
Rv0195 two component transcriptional regulator 412 47 textmining:409
Rv2751 hyp hypothetical protein 630 44 textmining:629
Rv0725c hyp hypothetical protein 630 44 textmining:629

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): mycolic acid synthase UmaA
  • Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=2e-112), Methyltransf_23 PF13489.13 (E=9e-10), Methyltransf_25 PF13649.13 (E=4e-09), Methyltransf_12 PF08242.19 (E=2e-08), Methyltransf_11 PF08241.19 (E=6e-06)
  • (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 YP_177729.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CMAS (PF02353.27), Methyltransf_23 (PF13489.13), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), Methyltransf_11 (PF08241.19)
  • 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 COG2230
  • Curated reference: UniProt Q6MX39 (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 — 12 functional partner(s); context anchor fadB2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0469|umaA
MTELRPFYEESQSIYDVSDEFFSLFLDPTMAYTCAYFEREDMTLEEAQNAKFDLALDKLHLEPGMTLLDIGCGWGGGLQRAIENYDVNVIGITLSRNQFEYSKAKLAKIPTERSVQVRLQGWDEFTDKVDRIVSIGAFEAFKMERYAAFFERSYDILPDDGRMLLHTILTYTQKQMHEMGVKVTMSDVRFMKFIGEEIFPGGQLPAQEDIFKFAQAADFSVEKVQLLQQHYARTLNIWAANLEANKDRAIALQSEEIYNKYMHYLTGCEHFFRKGISNVGQFTLTK