tesA Resolved · high auto-curated
H37Rv Rv2928 · MTBC0 mtbc0_003111 ·
261 aa · 3263195–3263980 (+) ·
RefSeq NP_217444.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | thioesterase TesA |
|---|---|
| MTBC0 PGAP re-annotation | thioesterase TesA |
| Revised (this work) | Thioesterase TesA. Pfam: Thioesterase (PF00975.27), 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 |
P9WQD5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Thioesterase TesA |
| EC (curated) |
EC 3.1.1.6, EC 3.1.2.-, EC 3.1.2.2
|
| Curated function | Involved in the synthesis of both phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), which are structurally related lipids non-covalently bound to the outer cell wall layer of M.tuberculosis and are important virulence factors. In vitro, TesA has both thioesterase and esterase activities. Exhibits thioesterase activity on acyl-CoA derivatives such as palmitoyl-CoA and decanoyl-CoA. Also displays hydrolytic activity on ester substrates, being more active on pNP esters with short carbon chain lengths (C2-C5) than with those bearing medium and long carbon chain lengths (C8-C18). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | tesA |
| eggNOG description | thioesterase |
| Orthologous group | COG3208 |
| Gene Ontology (47) |
GO:0005575, GO:0005623, GO:0005886, GO:0006629, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009273, GO:0009605, GO:0009607, GO:0009987 +35 more
|
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 | 0.3 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.89% of strains (1287) · 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 |
|---|---|---|---|---|
Thioesterase | PF00975.27 | 1.1e-68 | 30–253 | Thioesterase domain |
Abhydrolase_6 | PF12697.14 | 3.7e-09 | 39–240 | Alpha/beta hydrolase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ppsB (phthiocerol synthesis polyketide synthase type I PpsB), high confidence from genomic context alone (score 919 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 937 | 919 ctx | cooccurence:719 database:500 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 934 | 907 ctx | cooccurence:705 database:500 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 934 | 907 ctx | cooccurence:667 database:500 |
Rv3800c pks13 |
polyketide synthase | 940 | 905 ctx | cooccurence:483 coexpression:784 textmining:405 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 958 | 888 ctx | cooccurence:742 database:500 textmining:648 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 885 | 880 ctx | cooccurence:725 database:500 |
Rv0101 nrp |
peptide synthetase Nrp | 871 | 852 ctx | cooccurence:710 coexpression:446 |
Rv2380c mbtE |
peptide synthetase | 867 | 850 ctx | cooccurence:734 coexpression:415 |
Rv2383c mbtB |
phenyloxazoline synthase | 889 | 846 | coexpression:784 |
Rv1661 pks7 |
polyketide synthase | 868 | 828 ctx | cooccurence:693 |
Rv2048c pks12 |
polyketide synthase | 884 | 825 ctx | cooccurence:671 |
Rv0405 pks6 |
membrane bound polyketide synthase | 892 | 820 ctx | cooccurence:700 textmining:428 |
Rv2946c pks1 |
polyketide synthase | 868 | 814 ctx | cooccurence:639 |
Rv2929 hyp |
hypothetical protein | 810 | 810 ctx | neighborhood:801 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 860 | 771 ctx | cooccurence:568 textmining:417 |
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: thioesterase TesA
- MTBC0 PGAP product: thioesterase TesA
- Pfam (hmmscan --cut_ga): Thioesterase PF00975.27 (E=1e-68), Abhydrolase_6 PF12697.14 (E=4e-09)
- (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_217444.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thioesterase (PF00975.27), 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
COG3208 - Curated reference: UniProt P9WQD5 (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 —
61 functional partner(s); context anchor
ppsB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003111|Rv2928|tesA MLARHGPRYGGSVNGHSDDSSGDAKQAAPTLYIFPHAGGTAKDYVAFSREFSADVKRIAVQYPGQHDRSGLPPLESIPTLADEIFAMMKPSARIDDPVAFFGHSMGGMLAFEVALRYQSAGHRVLAFFVSACSAPGHIRYKQLQDLSDREMLDLFTRMTGMNPDFFTDDEFFVGALPTLRAVRAIAGYSCPPETKLSCPIYAFIGDKDWIATQDDMDPWRDRTTEEFSIRVFPGDHFYLNDNLPELVSDIEDKTLQWHDRA