lipQ Family assigned · medium auto-curated

H37Rv Rv2485c · MTBC0 mtbc0_002645 · 421 aa · 2815613–2816878 (-) · RefSeq NP_217001.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)carboxylesterase LipQ
MTBC0 PGAP re-annotationalpha/beta hydrolase
Revised (this work)Alpha/beta hydrolase. Pfam: COesterase (PF00135.35), BD-FAE (PF20434.6), Abhydrolase_3 (PF07859.20), Peptidase_S9 (PF00326.28).

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

Curated reference (UniProt)

UniProt I6Y9F7 SwissProt · reviewed · Evidence at protein level
UniProt nameEsterase LipQ
EC (curated) EC 3.1.1.-
Curated functionShows lipase activity. Is highly immunogenic and may play an important role in the virulence and pathogenesis of M.tuberculosis infection, by altering the balance of cytokines. Significantly down-regulates the expression level of pro-inflammatory cytokines (TNF and IFN-gamma) and up-regulates the level of anti-inflammatory cytokines such as IL-4 and IL-10 as compared to LPS stimulated macrophages. Also inhibits the expression of iNOS, TLR2 and transcription factor NF-kappa-B in LPS stimulated macrophages whereas the expression of TLR-4 remains unchanged.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namelipQ
eggNOG descriptionProlyl oligopeptidase family
Orthologous groupCOG0657

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 0.798 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 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
COesterasePF00135.35 7.7e-12154–262 Carboxylesterase family
BD-FAEPF20434.6 2.2e-47166–359 BD-FAE
Abhydrolase_3PF07859.20 2.4e-21176–379 alpha/beta hydrolase fold
Peptidase_S9PF00326.28 2.1e-13221–380 Prolyl oligopeptidase family

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

Closest characterised functional partner: Rv2484c (diacyglycerol O-acyltransferase), medium confidence from genomic context alone (score 558 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1549 fadD11.1 Possible fatty-acid-CoA ligase FadD11.1 (fatty-acid-CoA synthetase) (fatty-acid-CoA synthase); Rv1549, (MTCY48.16c), len: 175 aa. Possible f 884 839 coexpression:838
Rv1550 fadD11 fatty-acid--CoA ligase FadD11 807 800 coexpression:799
Rv0458 aldehyde dehydrogenase 748 740 coexpression:739
Rv0166 fadD5 fatty-acid--CoA ligase FadD5 582 581 coexpression:517
Rv0310c hyp hypothetical protein 567 564 experimental:439
Rv2484c diacyglycerol O-acyltransferase 740 558 ctx neighborhood:449 textmining:435
Rv1400c lipI lipase 794 493 ctx cooccurence:490 textmining:612
Rv0722 rpmD 50S ribosomal protein L30 493 493 database:490
Rv2482c plsB2 glycerol-3-phosphate acyltransferase 502 486 ctx neighborhood:458
Rv2903c lepB signal peptidase 502 483 database:464
Rv2970c lipN lipase/esterase LipN 743 473 ctx cooccurence:470 textmining:534
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 493 471 experimental:441
Rv2483c plsC bifunctional L-3-phosphoserine phosphatase/1-acyl-sn-glycerol-3-phosphate acyltransferase 632 469 ctx neighborhood:449
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 466 466 experimental:441
Rv3149 nuoE NADH-quinone oxidoreductase subunit E 465 466 experimental:440

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: carboxylesterase LipQ
  • MTBC0 PGAP product: alpha/beta hydrolase
  • Pfam (hmmscan --cut_ga): COesterase PF00135.35 (E=8e-12), BD-FAE PF20434.6 (E=2e-47), Abhydrolase_3 PF07859.20 (E=2e-21), Peptidase_S9 PF00326.28 (E=2e-13)
  • (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_217001.1)
  • Domains: Pfam-A via hmmscan --cut_ga — COesterase (PF00135.35), BD-FAE (PF20434.6), Abhydrolase_3 (PF07859.20), Peptidase_S9 (PF00326.28)
  • 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 COG0657
  • Curated reference: UniProt I6Y9F7 (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 — 63 functional partner(s); context anchor Rv2484c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002645|Rv2485c|lipQ
MHIASVTSRCSRAGAEALRQGAQLAADARDTCRAGALLLRGSPCAIGWVAGWLSAEFPARVVTGHALSRISPRSIGRFGTSWAAQRADQILHAALVDAFGPDFRDLVWHPTGEQSEAARRSGLLNLPHIPGPHRRYAAQTSDIPYGPGGRENLLDIWRRPDLAPGRRAPVLIQVPGGAWTINGKRPQAYPLMSRMVELGWICVSINYSKSPRCTWPAHIVDVKRAIAWVRENIADYGGDPDFITITGGSAGAHLAALAALSANDPALQPGFESADTAVQAAAPYYGVYDLTNAENMHEMMMPFLEHFVMRSRYVDNPGLFKAASPISYVHSEAPPFFVLHGEKDPMVPSAQSRAFSAALRDAGAATVSYAELPNAHHAFDLAATVRSRMVAEAVSDFLGVIYGRRMGARKGSLALSSPPAS