Rv3740c Family assigned · medium auto-curated

H37Rv Rv3740c · MTBC0 mtbc0_003964 · 448 aa · 4214954–4216300 (-) · RefSeq NP_218257.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)diacyglycerol O-acyltransferase
MTBC0 PGAP re-annotationwax ester/triacylglycerol synthase family O-acyltransferase
Revised (this work)Wax ester/triacylglycerol synthase family O-acyltransferase. Pfam: WS_DGAT_cat (PF03007.22), WS_DGAT_C (PF06974.19).

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

Curated reference (UniProt)

UniProt P9WKA5 SwissProt · reviewed · Evidence at protein level
UniProt namePutative diacyglycerol O-acyltransferase Rv3740c
EC (curated) EC 2.3.1.20
Curated functionUpon expression in E.coli has a weak triacylglycerol synthase function, making triacylglycerol (TG) from diolein and long-chain fatty acyl-CoA. Also functions weakly as a wax synthase, as it incorporates palmityl alcohol into wax esters in the presence of palmitoyl-CoA.

UniProt still lists this protein as Putative diacyglycerol O-acyltransferase Rv3740c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionWax ester synthase-like Acyl-CoA acyltransferase domain
Orthologous groupCOG1020
Gene Ontology (64) GO:0000302, GO:0001666, GO:0003674, GO:0003824, GO:0004144, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006629, GO:0006638, GO:0006639 +52 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 1.273 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 missense, 1 nonsense, 4 frameshift
Disruption 5 distinct premature-stop/frameshift site(s); most common in 0.64% of strains (931) · convergent

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
WS_DGAT_catPF03007.22 1.4e-981–257 Wax ester synthase/diacylglycerol acyltransferase catalytic domain
WS_DGAT_CPF06974.19 1.8e-40297–442 WS/DGAT C-terminal domain

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

Closest characterised functional partner: Rv3741c (oxidoreductase), high confidence from genomic context alone (score 981 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3741c oxidoreductase 980 981 ctx neighborhood:882 coexpression:822
Rv3742c oxidoreductase 978 979 ctx neighborhood:882 coexpression:804
Rv3097c lipY triacylglycerol lipase Lip 919 919 database:900
Rv2252 dagK diacylglycerol kinase 900 901 database:900
Rv3391 acrA1 acyl-CoA-reductase AcrA 771 762 ctx cooccurence:745
Rv1543 oxidoreductase 728 729 ctx cooccurence:722
Rv0547c oxidoreductase 669 669 ctx cooccurence:661
Rv2627c hyp hypothetical protein 664 652 ctx cooccurence:436
Rv0825c hyp hypothetical protein 600 600 ctx cooccurence:594
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 533 506 experimental:441
Rv2048c pks12 polyketide synthase 527 500 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 527 500 experimental:441
Rv2940c mas multifunctional mycocerosic acid synthase 527 500 experimental:441
Rv3743c ctpJ cation transporter ATPase J 500 500 ctx neighborhood:497
Rv1527c pks5 polyketide synthase 526 499 experimental:441

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: diacyglycerol O-acyltransferase
  • MTBC0 PGAP product: wax ester/triacylglycerol synthase family O-acyltransferase
  • Pfam (hmmscan --cut_ga): WS_DGAT_cat PF03007.22 (E=1e-98), WS_DGAT_C PF06974.19 (E=2e-40)
  • (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_218257.1)
  • Domains: Pfam-A via hmmscan --cut_ga — WS_DGAT_cat (PF03007.22), WS_DGAT_C (PF06974.19)
  • 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 COG1020
  • Curated reference: UniProt P9WKA5 (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 — 27 functional partner(s); context anchor Rv3741c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003964|Rv3740c|
MSPIDALFLSAESREHPLHVGALQLFEPPAGAGRGFVRETYQAMLQCREIAPLFRKRPTSLHGALINLGWSTDADVDLGYHARRSALPAPGRVRELLELTSRLHSNLLDRHRPLWETHVIEGLRDGRFAIYSKMHHALVDGVSGLTLMRQPMTTDPIEGKLRTAWSPATQHTAIKRRRGRLQQLGGMLGSVAGLAPSTLRLARSALIEQQLTLPFGAPHTMLNVAVGGARRCAAQSWPLDRVKAVKDAAGVSLNDVVLAMCAGALREYLDDNDALPDTPLVAMVPVSLRTDRDSVGGNMVGAVLCNLATHLDDPADRLNAIHASMRGNKNVLSQLPRAQALAVSLLLLSPAALNTLPGLAKATPPPFNVCISNVPGAREPLYFNGARMVGNYPMSLVLDGQALNITLTSTADSLDFGVVGCRRSVPHVQRVLSHLETSLKELERAVGL