nlhH Family assigned · medium auto-curated
H37Rv Rv1399c · MTBC0 mtbc0_001500 ·
319 aa · 1584194–1585153 (-) ·
RefSeq NP_215915.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | carboxylesterase NlhH |
|---|---|
| MTBC0 PGAP re-annotation | alpha/beta hydrolase |
| Revised (this work) | Alpha/beta hydrolase. Pfam: BD-FAE (PF20434.6), COesterase (PF00135.35), 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 |
P9WK87
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Carboxylesterase NlhH |
| EC (curated) |
EC 3.1.1.1
|
| Curated function | Hydrolyzes various short-chain esters, such as triacylglycerols and vinyl esters. Has no activity against emulsified substrates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | lipH |
| eggNOG description | alpha/beta hydrolase fold |
| Orthologous group | COG0657 |
| Gene Ontology (9) |
GO:0003674, GO:0003824, GO:0008150, GO:0008152, GO:0009056, GO:0016787, GO:0016788, GO:0034338, GO:0052689
|
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 | 1.087 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 9 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 | 1.5e-22 | 71–175 | BD-FAE |
COesterase | PF00135.35 | 1.1e-14 | 71–168 | Carboxylesterase family |
Abhydrolase_3 | PF07859.20 | 9.4e-73 | 84–293 | alpha/beta hydrolase fold |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lipI (lipase), high confidence from genomic context alone (score 866 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1400c lipI |
lipase | 871 | 866 ctx | neighborhood:827 |
Rv1402 priA |
primosomal protein N' | 682 | 683 ctx | neighborhood:678 |
Rv1401 |
membrane protein | 630 | 630 ctx | neighborhood:626 |
Rv1393c |
monoxygenase | 624 | 622 ctx | neighborhood:544 |
Rv1397c vapC10 |
ribonuclease VapC10 | 605 | 605 ctx | neighborhood:604 |
Rv1398c vapB10 |
antitoxin VapB10 | 604 | 604 ctx | neighborhood:604 |
Rv3097c lipY |
triacylglycerol lipase Lip | 842 | 558 ctx | cooccurence:558 textmining:658 |
Rv0722 rpmD |
50S ribosomal protein L30 | 494 | 494 | 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 | 456 | 457 | experimental:440 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 478 | 454 | experimental:441 |
Rv3150 nuoF |
NADH-quinone oxidoreductase subunit F | 449 | 449 | experimental:441 |
Rv3149 nuoE |
NADH-quinone oxidoreductase subunit E | 449 | 449 | experimental:440 |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 431 | 431 | 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: carboxylesterase NlhH
- MTBC0 PGAP product: alpha/beta hydrolase
- Pfam (hmmscan --cut_ga): BD-FAE PF20434.6 (E=1e-22), COesterase PF00135.35 (E=1e-14), Abhydrolase_3 PF07859.20 (E=9e-73)
- (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_215915.1)
- Domains: Pfam-A via hmmscan --cut_ga — BD-FAE (PF20434.6), COesterase (PF00135.35), 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 P9WK87 (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
lipI - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001500|Rv1399c|nlhH MTEPTVARPDIDPVLKMLLDTFPVTFTAADGVEVARARLRQLKTPPELLPELRIEERTVGYDGLTDIPVRVYWPPVVRDNLPVVVYYHGGGWSLGGLDTHDPVARAHAVGAQAIVVSVDYRLAPEHPYPAGIDDSWAALRWVGENAAELGGDPSRIAVAGDSAGGNISAVMAQLARDVGGPPLVFQLLWYPTTMADLSLPSFTENADAPILDRDVIDAFLAWYVPGLDISDHTMLPTTLAPGNADLSGLPPAFIGTAEHDPLRDDGACYAELLTAAGVSVELSNEPTMVHGYVNFALVVPAAAEATGRGLAALKRALHA