tgs1 Resolved · high auto-curated

H37Rv Rv3130c · MTBC0 mtbc0_003327 · 463 aa · 3516340–3517731 (-) · RefSeq NP_217646.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)diacyglycerol O-acyltransferase
MTBC0 PGAP re-annotationdiacylglycerol O-acyltransferase
Revised (this work)Diacylglycerol 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 P9WKC9 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable diacyglycerol O-acyltransferase tgs1
EC (curated) EC 2.3.1.20
Curated functionCatalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for storage lipid synthesis (Probable)..; FUNCTION: Upon expression in E.coli functions as a triacylglycerol synthase, making triacylglycerol (TG) from diolein and long-chain fatty acyl-CoA. Prefers C(26:0)-CoA over C(18:1)-CoA. TG synthesis activity increases in M.tuberculosis upon oxygen depletion and NO treatment, with concomitant accumulation of TG in inclusion bodies. As disruption of the gene encoding this protein obviates TG synthesis this seems .

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionBelongs to the long-chain O-acyltransferase family
Orthologous groupCOG1020
EC number EC 2.3.1.20
KEGG orthology K00635
KEGG pathways map00561, map01100
KEGG modules M00089
Gene Ontology (60) GO:0000302, GO:0001666, GO:0003674, GO:0003824, GO:0004144, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006629, GO:0006638, GO:0006639 +48 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 0.561 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 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
WS_DGAT_catPF03007.22 4.3e-824–256 Wax ester synthase/diacylglycerol acyltransferase catalytic domain
WS_DGAT_CPF06974.19 2.4e-28299–441 WS/DGAT C-terminal domain

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

Closest characterised functional partner: Rv3131 (NAD(P)H nitroreductase), high confidence from genomic context alone (score 949 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3131 NAD(P)H nitroreductase 980 949 ctx neighborhood:506 coexpression:863 textmining:626
Rv2627c hyp hypothetical protein 922 919 ctx cooccurence:432 coexpression:804
Rv3097c lipY triacylglycerol lipase Lip 925 901 database:900
Rv2252 dagK diacylglycerol kinase 900 900 database:900
Rv3127 hyp hypothetical protein 913 889 coexpression:863
Rv2032 acg NAD(P)H nitroreductase 925 874 coexpression:835 textmining:438
Rv2031c hspX alpha-crystallin 942 862 coexpression:861 textmining:602
Rv1738 hyp hypothetical protein 909 861 coexpression:861
Rv0079 hyp hypothetical protein 901 860 coexpression:860
Rv1996 universal stress protein 878 860 coexpression:860
Rv2007c fdxA ferredoxin 921 836 coexpression:836 textmining:541
Rv3134c universal stress protein 879 813 coexpression:813
Rv2626c hrp1 hypoxic response protein 867 811 coexpression:810
Rv0080 hyp hypothetical protein 852 803 coexpression:803
Rv1733c transmembrane protein 845 802 coexpression:802

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: diacylglycerol O-acyltransferase
  • Pfam (hmmscan --cut_ga): WS_DGAT_cat PF03007.22 (E=4e-82), WS_DGAT_C PF06974.19 (E=2e-28)
  • (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_217646.1)
  • 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 P9WKC9 (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 — 46 functional partner(s); context anchor Rv3131
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003327|Rv3130c|tgs1
MNHLTTLDAGFLKAEDVDRHVSLAIGALAVIEGPAPDQEAFLSSLAQRLRPCTRFGQRLRLRPFDLGAPKWVDDPDFDLGRHVWRIALPRPGNEDQLFELIADLMARRLDRGRPLWEVWVIEGLADSKWAILTKLHHCMADGIAATHLLAGLSDESMSDSFASNIHTTMQSQSASVRRGGFRVNPSEALTASTAVMAGIVRAAKGASEIAAGVLSPAASSLNGPISDLRRYSAAKVPLADVEQVCRKFDVTINDVALAAITESYRNVLIQRGERPRFDSLRTLVPVSTRSNSALSKTDNRVSLMLPNLPVDQENPLQRLRIVHSRLTRAKAGGQRQFGNTLMAIANRLPFPMTAWAVGLLMRLPQRGVVTVATNVPGPRRPLQIMGRRVLDLYPVSPIAMQLRTSVAMLSYADDLYFGILADYDVVADAGQLARGIEDAVARLVAISKRRKVTRRRGALSLVV