lipC Resolved · high auto-curated
H37Rv Rv0220 · MTBC0 mtbc0_000234 ·
403 aa · 263193–264404 (+) ·
RefSeq NP_214734.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | esterase LipC |
|---|---|
| MTBC0 PGAP re-annotation | esterase LipC |
| Revised (this work) | Esterase LipC. 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 |
P96402
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Esterase LipC |
| EC (curated) |
EC 3.1.1.-
|
| Curated function | Esterase that can hydrolyze short-chain esters with the carbon chain containing 2 to 10 carbon atoms. Does not have lipase activity. Is highly immunogenic and elicits strong humoral immune responses in both HIV-negative (HIV-) and HIV-positive (HIV+) tuberculosis (TB) patients. Also elicits pro-inflammatory cytokine and chemokine responses from macrophages and pulmonary epithelial cells. May participate in the progression of active tuberculosis both by contributing to the utilization of lipid substrates for bacterial growth and replication, and by modulating immune responses. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | lipC |
| eggNOG description | Alpha beta hydrolase |
| Orthologous group | COG0657 |
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 | 0.622 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
COesterase | PF00135.35 | 6.4e-09 | 143–244 | Carboxylesterase family |
BD-FAE | PF20434.6 | 1.7e-45 | 144–349 | BD-FAE |
Abhydrolase_3 | PF07859.20 | 4.5e-25 | 160–369 | alpha/beta hydrolase fold |
Peptidase_S9 | PF00326.28 | 4.2e-10 | 210–369 | Prolyl oligopeptidase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0218 (transmembrane protein), high confidence from genomic context alone (score 869 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0218 |
transmembrane protein | 868 | 869 ctx | neighborhood:867 |
Rv0217c lipW |
esterase LipW | 972 | 848 ctx | neighborhood:623 cooccurence:614 textmining:825 |
Rv0221 |
diacyglycerol O-acyltransferase | 908 | 845 ctx | neighborhood:818 textmining:431 |
Rv0219 |
transmembrane protein | 796 | 796 ctx | neighborhood:796 |
Rv0222 echA1 |
enoyl-CoA hydratase EchA1 | 790 | 790 ctx | neighborhood:783 |
Rv0310c hyp |
hypothetical protein | 536 | 533 | experimental:439 |
Rv0722 rpmD |
50S ribosomal protein L30 | 495 | 495 | database:490 |
Rv2903c lepB |
signal peptidase | 505 | 487 | database:464 |
Rv1076 lipU |
lipase LipU | 810 | 473 ctx | cooccurence:471 textmining:656 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 464 | 465 | experimental:440 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 643 | 463 | experimental:441 |
Rv3149 nuoE |
NADH-quinone oxidoreductase subunit E | 454 | 454 | experimental:440 |
Rv3150 nuoF |
NADH-quinone oxidoreductase subunit F | 449 | 449 | experimental:441 |
Rv3487c lipF |
carboxylesterase LipF | 796 | 440 ctx | cooccurence:432 textmining:652 |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 433 | 434 | 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: esterase LipC
- MTBC0 PGAP product: esterase LipC
- Pfam (hmmscan --cut_ga): COesterase PF00135.35 (E=6e-09), BD-FAE PF20434.6 (E=2e-45), Abhydrolase_3 PF07859.20 (E=5e-25), Peptidase_S9 PF00326.28 (E=4e-10)
- (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_214734.1)
- 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 P96402 (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 —
58 functional partner(s); context anchor
Rv0218 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000234|Rv0220|lipC MNQRRAAGSTGVAYIRWLLRARPADYMLALSVAGGSLPVVGKHLKPLGGVTAIGVWGARHASDFLSATAKDLLTPGINEVRRRDRASTQEVSVAALRGIVSPDDLAVEWPAPERTPPVCGALRHRRYVHRRRVLYGDDPAQLLDVWRRKDMPTKPAPVLIFVPGGAWVHGSRAIQGYAVLSRLAAQGWVCLSIDYRVAPHHRWPRHILDVKTAIAWARANVDKFGGDRNFIAVAGCSAGGHLSALAGLTANDPQYQAELPEGSDTSVDAVVGIYGRYDWEDRSTPERARFVDFLERVVVQRTIDRHPEVFRDASPIQRVTRNAPPFLVIHGSRDCVIPVEQARSFVERLRAVSRSQVGYLELPGAGHGFDLLDGARTGPTAHAIALFLNQVHRSRAQFAKEVI