tgs4 Family assigned · medium auto-curated

H37Rv Rv3088 · MTBC0 mtbc0_003282 · 474 aa · 3475704–3477128 (+) · RefSeq NP_217604.1

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 P9WKC3 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable diacyglycerol O-acyltransferase Tgs4
EC (curated) EC 2.3.1.20
Curated functionRequired for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH. Upon expression in E.coli functions as a triacylglycerol synthase, making triacylglycerol (TG) from diolein and long-chain fatty acyl-CoA. Has very weak wax synthase activity, incorporating palmityl alcohol into wax esters in the presence of palmitoyl-CoA.

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 (62) GO:0000302, GO:0001666, GO:0003674, GO:0003824, GO:0004144, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006629, GO:0006638, GO:0006639 +50 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 0.782 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 9 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (225) · 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
WS_DGAT_catPF03007.22 5.6e-835–273 Wax ester synthase/diacylglycerol acyltransferase catalytic domain
WS_DGAT_CPF06974.19 9.2e-30313–457 WS/DGAT C-terminal domain

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

Closest characterised functional partner: fadD13 (long chain-fatty-acid--CoA ligase FadD13), high confidence from genomic context alone (score 983 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3089 fadD13 long chain-fatty-acid--CoA ligase FadD13 997 983 ctx neighborhood:882 coexpression:860 textmining:833
Rv3087 diacyglycerol O-acyltransferase 988 983 ctx neighborhood:833 coexpression:860
Rv3086 adhD alcohol dehydrogenase D 978 955 ctx neighborhood:693 coexpression:860 textmining:546
Rv3083 mymA FAD-containing monooxygenase MymA 990 951 ctx neighborhood:616 coexpression:860 textmining:803
Rv3085 sadH oxidoreductase SadH 975 951 ctx neighborhood:616 coexpression:860 textmining:510
Rv3084 lipR acetyl-hydrolase LipR 974 944 ctx neighborhood:616 coexpression:860 textmining:557
Rv3097c lipY triacylglycerol lipase Lip 927 925 database:900
Rv2252 dagK diacylglycerol kinase 900 901 database:900
Rv3233c Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 857 760 ctx cooccurence:760 textmining:431
Rv3391 acrA1 acyl-CoA-reductase AcrA 845 673 ctx cooccurence:669 textmining:546
Rv1543 oxidoreductase 775 658 ctx cooccurence:656
Rv3082c virS HTH-type transcriptional regulator VirS 595 595 ctx neighborhood:441
Rv2627c hyp hypothetical protein 591 592 ctx cooccurence:588
Rv1192 hyp hypothetical protein 572 573 ctx cooccurence:570
Rv0547c oxidoreductase 571 572 ctx cooccurence:569

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=6e-83), WS_DGAT_C PF06974.19 (E=9e-30)
  • (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_217604.1)
  • 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 P9WKC3 (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 — 31 functional partner(s); context anchor fadD13
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003282|Rv3088|tgs4
MTRINPIDLSFLLLERANRPNHMAAYTIFEKPKGQKSSFGPRLFDAYRHSQAAKPFNHKLKWLGTDVAAWETVEPDMGYHIRHLALPAPGSMQQFHETVSFLNTGLLDRGHPMWECYIIDGIERGRIAILLKVHHALIDGEGGLRAMRNFLSDSPDDTTLAGPWMSAQGADRPRRTPATVSRRAQLQGQLQGMIKGLTKLPSGLFGVSADAADLGAQALSLKARKASLPFTARRTLFNNTAKSAARAYGNVELPLADVKALAKATGTSVNDVVMTVIDDALHHYLAEHQASTDRPLVAFMPMSLREKSGEGGGNRVSAELVPMGAPKASPVERLKEINAATTRAKDKGRGMQTTSRQAYALLLLGSLTVADALPLLGKLPSANVVISNMKGPTEQLYLAGAPLVAFSGLPIVPPGAGLNVTFASINTALCIAIGAAPEAVHEPSRLAELMQRAFTELQTEAGTTSPTTSKSRTP