lipL Family assigned · medium auto-curated
H37Rv Rv1497 · MTBC0 mtbc0_001601 ·
429 aa · 1697746–1699035 (+) ·
RefSeq NP_216013.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | esterase LipL |
|---|---|
| MTBC0 PGAP re-annotation | serine hydrolase domain-containing protein |
| Revised (this work) | Serine hydrolase domain-containing protein. Pfam: Beta-lactamase (PF00144.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71778
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Esterase/beta-lactamase LipL |
| EC (curated) |
EC 3.1.1.-, EC 3.5.2.6
|
| Curated function | Shows both esterase and beta-lactamase activities, with a much higher activity against phenyl esters than against beta-lactams. Shows esterase activity against both long-chain and short-chain p-nitrophenol (pNP) esters, with a preference for shorter chain esters. Hydrolyzes substrates containing beta-lactam ring such as nitrocefin and ampicillin. Functions as an immunogen that activates both humoral and cell-mediated responses. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| Preferred name | lipL |
| eggNOG description | beta-lactamase |
| Orthologous group | COG1680 |
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 | 0.241 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (209) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Beta-lactamase | PF00144.30 | 9.4e-59 | 46–382 | Beta-lactamase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: meaB (transport system kinase), medium confidence from genomic context alone (score 658 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1477 ripA |
peptidoglycan endopeptidase RipA | 763 | 753 | coexpression:745 |
Rv1478 ripB |
peptidoglycan endopeptidase RipB | 754 | 746 | coexpression:742 |
Rv1496 meaB |
transport system kinase | 657 | 658 ctx | neighborhood:654 |
Rv1492 mutA |
methylmalonyl-CoA mutase small subunit | 638 | 637 ctx | neighborhood:633 |
Rv1495 mazF4 |
mRNA interferase MazF4 | 625 | 625 ctx | neighborhood:619 |
Rv1494 mazE4 |
antitoxin MazE4 | 622 | 621 ctx | neighborhood:619 |
Rv1493 mutB |
methylmalonyl-CoA mutase large subunit | 619 | 619 ctx | neighborhood:613 |
Rv1367c hyp |
hypothetical protein | 541 | 541 ctx | cooccurence:541 |
Rv3633 hyp |
hypothetical protein | 533 | 533 ctx | cooccurence:527 |
Rv1491c |
TVP38/TMEM64 family membrane protein | 463 | 464 ctx | neighborhood:458 |
Rv2913c |
D-amino acid aminohydrolase | 414 | 414 | |
Rv3775 lipE |
lipase LipE | 507 | 306 | |
Rv2463 lipP |
esterase/lipase LipP | 484 | 284 | |
Rv1076 lipU |
lipase LipU | 754 | 168 | textmining:717 |
Rv2068c blaC |
beta-lactamase | 525 | 166 | textmining:455 |
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 LipL
- MTBC0 PGAP product: serine hydrolase domain-containing protein
- Pfam (hmmscan --cut_ga): Beta-lactamase PF00144.30 (E=9e-59)
- (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_216013.1)
- Domains: Pfam-A via hmmscan --cut_ga — Beta-lactamase (PF00144.30)
- 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
COG1680 - Curated reference: UniProt P71778 (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 —
25 functional partner(s); context anchor
meaB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001601|Rv1497|lipL MMVDTGVDHRAVSSHDGPDAGRRVFGAADPRFACVVRAFASMFPGRRFGGGALAVYLDGQPVVDVWKGWADRAGWVPWSADSAPMVFSATKGMTATVIHRLADRGLIDYEAPVAEYWPAFGANGKATLTVRDVMRHQAGLSGLRGATQQDLLDHVVMEERLAAAVPGRLLGKSAYHALTFGWLMSGLARAVTGKDMRLLFREELAEPLDTDGLHLGRPPADAPTRVAEIIMPQDIAANAVLTCAMRRLAHRFSGGFRSMYFPGAIAAVQGEAPLLDAEIPAANGVATARALARMYGAIANGGEIDGIRFLSRELVTGLTRNRRQVLPDRNLLVPLNFHLGYHGMPIGNVMPGFGHVGLGGSIGWTDPETGVAFALVHNRLLSPLVMTDHAGFVGIYHLIRQAAAQARKRGYQPVTPFGAPYSEPGAAAG