lipR Family assigned · medium auto-curated

H37Rv Rv3084 · MTBC0 mtbc0_003278 · 308 aa · 3471361–3472287 (+) · RefSeq NP_217600.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acetyl-hydrolase LipR
MTBC0 PGAP re-annotationalpha/beta hydrolase
Revised (this work)Alpha/beta hydrolase. Pfam: Say1_Mug180 (PF10340.16), Abhydrolase_3 (PF07859.20).

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

Curated reference (UniProt)

UniProt P9WK85 SwissProt · reviewed · Evidence at protein level
UniProt namePutative acetyl-hydrolase LipR
EC (curated) EC 3.1.1.-
Curated functionRequired for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH.

UniProt still lists this protein as Putative acetyl-hydrolase LipR; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namelipR
eggNOG descriptionalpha/beta hydrolase fold
Orthologous groupCOG0657
Gene Ontology (27) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0008152, GO:0009056, GO:0009268, GO:0009628, GO:0010447, GO:0016020 +15 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 1.027 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 10 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 0.37% of strains (538) · 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
Say1_Mug180PF10340.16 1.6e-1071–191 Steryl acetyl hydrolase
Abhydrolase_3PF07859.20 5.2e-4472–272 alpha/beta hydrolase fold

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

Closest characterised functional partner: mymA (FAD-containing monooxygenase MymA), high confidence from genomic context alone (score 984 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3083 mymA FAD-containing monooxygenase MymA 994 984 ctx neighborhood:882 coexpression:869 textmining:660
Rv3085 sadH oxidoreductase SadH 997 983 ctx neighborhood:882 coexpression:860 textmining:870
Rv3086 adhD alcohol dehydrogenase D 991 960 ctx neighborhood:721 coexpression:862 textmining:803
Rv3089 fadD13 long chain-fatty-acid--CoA ligase FadD13 988 953 ctx neighborhood:616 coexpression:866 textmining:759
Rv3088 tgs4 diacyglycerol O-acyltransferase 974 944 ctx neighborhood:616 coexpression:860 textmining:557
Rv3087 diacyglycerol O-acyltransferase 976 941 ctx neighborhood:590 coexpression:863 textmining:616
Rv3082c virS HTH-type transcriptional regulator VirS 611 611 ctx neighborhood:602
Rv0722 rpmD 50S ribosomal protein L30 492 493 database:490
Rv2903c lepB signal peptidase 501 482 database:464
Rv0310c hyp hypothetical protein 477 474 experimental:439
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 457 457 experimental:440
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 476 453 experimental:441
Rv3149 nuoE NADH-quinone oxidoreductase subunit E 448 448 experimental:440
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 446 446 experimental:441
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 439 433 experimental:426

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: acetyl-hydrolase LipR
  • MTBC0 PGAP product: alpha/beta hydrolase
  • Pfam (hmmscan --cut_ga): Say1_Mug180 PF10340.16 (E=2e-10), Abhydrolase_3 PF07859.20 (E=5e-44)
  • (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_217600.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Say1_Mug180 (PF10340.16), Abhydrolase_3 (PF07859.20)
  • 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 P9WK85 (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 mymA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003278|Rv3084|lipR
MNLRKNVIRSVLRGARPLFASRRLGIAGRRVLLATLTAGARAPKGTRFQRVSIAGVPVQRVQPPHAATSGTLIYLHGGAYALGSARGYRGLAAQLAAAAGMTALVPDYTRAPHAHYPVALEEMAAVYTRLLDDGLDPKTTVIAGDSAGGGLTLALAMALRDRGIQAPAALGLICPWADLAVDIEATRPALRDPLILPSMCTEWAPRYVGSSDPRLPGISPVYGDMSGLPPIVMQTAGDDPICVDADKIETACAASKTSIEHRRFAGMWHDFHLQVSLLPEARDAIADLGARLRGHLHQSQGQPRGVVK