lipG Resolved · high auto-curated

H37Rv Rv0646c · MTBC0 mtbc0_000684 · 301 aa · 743787–744692 (-) · RefSeq NP_215160.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipase/esterase LipG
MTBC0 PGAP re-annotationlipase/esterase LipG
Revised (this work)Lipase/esterase LipG. Pfam: Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14).

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

Curated reference (UniProt)

UniProt P96935 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable lipase/esterase LipG

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namelipG
eggNOG descriptionAlpha beta hydrolase
Orthologous groupCOG2267

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 0.523 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
Abhydrolase_1PF00561.27 9.6e-2326–280 alpha/beta hydrolase fold
Hydrolase_4PF12146.16 4.9e-1229–281 Serine aminopeptidase, S33
Abhydrolase_6PF12697.14 1.4e-1333–283 Alpha/beta hydrolase family

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

Closest characterised functional partner: mmaA1 (mycolic acid methyltransferase MmaA1), medium confidence from genomic context alone (score 681 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0647c hyp hypothetical protein 996 965 ctx neighborhood:876 coexpression:733 textmining:907
Rv0645c mmaA1 mycolic acid methyltransferase MmaA1 848 681 ctx neighborhood:675 textmining:543
Rv0648 alpha-mannosidase 615 615 ctx neighborhood:552
Rv0650 sugar kinase 538 538 ctx neighborhood:538
Rv0649 fabD2 malonyl CoA-acyl carrier protein transacylase 537 537 ctx neighborhood:537
Rv0221 diacyglycerol O-acyltransferase 516 517 ctx cooccurence:512
Rv2940c mas multifunctional mycocerosic acid synthase 535 507 experimental:441
Rv2048c pks12 polyketide synthase 533 506 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 531 503 experimental:441
Rv3088 tgs4 diacyglycerol O-acyltransferase 503 503 ctx cooccurence:503
Rv1527c pks5 polyketide synthase 529 501 experimental:441
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 527 500 experimental:441
Rv2285 diacylglycerol acyltransferase 491 491 ctx cooccurence:491
Rv3480c diacyglycerol O-acyltransferase 485 485 ctx cooccurence:485
Rv2946c pks1 polyketide synthase 500 470

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: lipase/esterase LipG
  • MTBC0 PGAP product: lipase/esterase LipG
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=1e-22), Hydrolase_4 PF12146.16 (E=5e-12), Abhydrolase_6 PF12697.14 (E=1e-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_215160.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14)
  • 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 COG2267
  • Curated reference: UniProt P96935 (TrEMBL, unreviewed; 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 — 40 functional partner(s); context anchor mmaA1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000684|Rv0646c|lipG
MDIRSGTAVSGDVKLYYEDMGDLDHPPVLLIMGLGAQMLLWRTDFCARLVAKGLRVIRYDNRDVGLSTKTERHRPGQPLATRLVRSWLGLPSQAAYTLEDMAADAAALLDHLDVKHAHVVGASMGGMIAQIFAARFAQRTKTLAVIFSSNNHRFLPPPAPRALLALLTGPPPDSPRDVIVDNAVRVSKIIGSPAYPIPEDQVRAEAAESYDRNFHPWGIAQQFSAILGSGSLLRYDRRIVAPTVVIHGRADKLMRPFGGRAVARAINGARLVLIDGMGHDLPRQLWDRVIGELTRNFSEAG