lipU Resolved · high auto-curated
H37Rv Rv1076 · MTBC0 - ·
297 aa · 1200767–1201660 (+) ·
RefSeq NP_215592.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipase LipU |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Lipase LipU. Pfam: BD-FAE (PF20434.6), 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.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O53424
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Esterase LipU |
| EC (curated) |
EC 3.1.1.-
|
| Curated function | Esterase that shows preference for short chain fatty acids. Contributes to the growth of M.tuberculosis during the nutritive stress. Elicits strong humoral response in both extrapulmonary and relapsed cases of tuberculosis patients. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | lipU |
| 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 | 0.484 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 |
|---|---|---|---|---|
BD-FAE | PF20434.6 | 5.1e-08 | 62–151 | BD-FAE |
Say1_Mug180 | PF10340.16 | 2.2e-08 | 65–184 | Steryl acetyl hydrolase |
Abhydrolase_3 | PF07859.20 | 1.3e-45 | 66–272 | alpha/beta hydrolase fold |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cbs (cystathionine beta-synthase), high confidence from genomic context alone (score 864 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1077 cbs |
cystathionine beta-synthase | 865 | 864 ctx | neighborhood:804 |
Rv3097c lipY |
triacylglycerol lipase Lip | 880 | 755 ctx | cooccurence:755 textmining:533 |
Rv1075c hyp |
hypothetical protein | 718 | 706 ctx | neighborhood:614 |
Rv1078 pra hyp |
hypothetical protein | 661 | 661 ctx | neighborhood:659 |
Rv0722 rpmD |
50S ribosomal protein L30 | 491 | 492 | database:490 |
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA | 488 | 486 ctx | neighborhood:468 |
Rv2903c lepB |
signal peptidase | 502 | 483 | database:464 |
Rv0310c hyp |
hypothetical protein | 480 | 477 | experimental:439 |
Rv0220 lipC |
esterase LipC | 810 | 473 ctx | cooccurence:471 textmining:656 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 468 | 453 | experimental:440 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 472 | 449 | experimental:441 |
Rv3149 nuoE |
NADH-quinone oxidoreductase subunit E | 446 | 444 | experimental:440 |
Rv3150 nuoF |
NADH-quinone oxidoreductase subunit F | 444 | 444 | experimental:441 |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 462 | 436 | experimental:426 |
Rv2946c pks1 |
polyketide synthase | 473 | 421 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): lipase LipU
- Pfam (hmmscan --cut_ga): BD-FAE PF20434.6 (E=5e-08), Say1_Mug180 PF10340.16 (E=2e-08), Abhydrolase_3 PF07859.20 (E=1e-45)
- (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_215592.1)
- Domains: Pfam-A via hmmscan --cut_ga — BD-FAE (PF20434.6), 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 O53424 (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 —
49 functional partner(s); context anchor
cbs - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1076|lipU MAVRPVLAVGSYLPHAPWPWGVIDQAARVLLPASTTVRAAVSLPNASAQLVRASGVLPADGTRRAVLYLHGGAFLTCGANSHGRLVELLSKFADSPVLVVDYRLIPKHSIGMALDDCHDGYRWLRLLGYEPEQIVLAGDSAGGYLALALAQRLQEVGEEPAALVAISPLLQLAKEHKQAHPNIKTDAMFPARAFDALDALVASAAARNQVDGEPEELYEPLEHITPGLPRTLIHVSGSEVLLHDAQLAAAKLAAAGVPAEVRVWPGQVHDFQVAASMLPEAIRSLRQIGEYIREATG