caeA Resolved · high auto-curated
H37Rv Rv2224c · MTBC0 mtbc0_002361 ·
520 aa · 2521618–2523180 (-) ·
RefSeq NP_216740.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | carboxylesterase A |
|---|---|
| MTBC0 PGAP re-annotation | carboxylesterase CaeA |
| Revised (this work) | Carboxylesterase CaeA. Pfam: Abhydrolase_1 (PF00561.27), Abhydrolase_4 (PF08386.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHR3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine protease Hip1 |
| EC (curated) |
EC 3.4.21.-
|
| Curated function | Serine protease that promotes tuberculosis (TB) pathogenesis by promoting the processing and the extracellular release of the M.tuberculosis (Mtb) heat-shock protein GroEL2. Hip1-dependent cleavage of multimeric GroEL2 results in release of cleaved monomeric GroEL2 into the extracellular milieu. Conversion of multimeric GroEL2 into monomeric GroEL2 is likely to be a mechanism for regulating GroEL2 functions during Mtb pathogenesis. In vitro, exhibits proteolytic activity against synthetic peptides and the general protease substrate azocasein, and exhibits esterase activity against the ester su. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | caeA |
| eggNOG description | Alpha beta hydrolase |
| Orthologous group | COG0596 |
| Gene Ontology (48) |
GO:0003674, GO:0003824, GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006464, GO:0006807, GO:0008150 +36 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 | 0.239 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 5 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 |
|---|---|---|---|---|
Abhydrolase_1 | PF00561.27 | 1.9e-41 | 104–496 | alpha/beta hydrolase fold |
Abhydrolase_4 | PF08386.17 | 5.4e-22 | 421–520 | TAP-like protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: glnA2 (glutamine synthetase), high confidence from genomic context alone (score 728 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2222c glnA2 |
glutamine synthetase | 732 | 728 ctx | neighborhood:725 |
Rv2221c glnE |
[glutamate--ammonia-ligase | 707 | 693 ctx | neighborhood:693 |
Rv2223c caeB |
carboxylesterase B | 648 | 638 ctx | neighborhood:618 |
Rv2256c hyp |
hypothetical protein | 562 | 562 ctx | cooccurence:562 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 526 | 498 | experimental:441 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 526 | 498 | experimental:441 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 526 | 498 | experimental:441 |
Rv2048c pks12 |
polyketide synthase | 526 | 498 | experimental:441 |
Rv1527c pks5 |
polyketide synthase | 526 | 498 | experimental:441 |
Rv2946c pks1 |
polyketide synthase | 486 | 455 | |
Rv1661 pks7 |
polyketide synthase | 449 | 424 | |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 449 | 424 | |
Rv1663 pks17 |
polyketide synthase | 431 | 410 | |
Rv3671c marP |
serine protease | 581 | 360 | |
Rv0125 pepA |
serine protease PepA | 470 | 360 |
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 A
- MTBC0 PGAP product: carboxylesterase CaeA
- Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=2e-41), Abhydrolase_4 PF08386.17 (E=5e-22)
- (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_216740.1)
- Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Abhydrolase_4 (PF08386.17)
- 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
COG0596 - Curated reference: UniProt P9WHR3 (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 —
23 functional partner(s); context anchor
glnA2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002361|Rv2224c|caeA MGMRLSRRDKIARMLLIWAALAAVALVLVGCIRVVGGRARMAEPKLGQPVEWTPCRSSNPQVKIPGGALCGKLAVPVDYDRPDGDVAALALIRFPATGDKIGSLVINPGGPGESGIEAALGVFQTLPKRVHERFDLVGFDPRGVASSRPAIWCNSDADNDRLRAEPQVDYSREGVAHIENETKQFVGRCVDKMGKNFLAHVGTVNVAKDLDAIRAALGDDKLTYLGYSYGTRIGSAYAEEFPQRVRAMILDGAVDPNADPIEAELRQAKGFQDAFNNYAADCAKNAGCPLGADPAKAVEVYHSLVDPLVDPDNPRISRPARTKDPRGLSYSDAIVGTIMALYSPNLWQHLTDGLSELVDNRGDTLLALADMYMRRDSHGRYNNSGDARVAINCVDQPPVTDRDKVIDEDRRAREIAPFMSYGKFTGDAPLGTCAFWPVPPTSQPHAVSAPGLVPTVVVSTTHDPATPYKAGVDLANQLRGSLLTFDGTQHTVVFQGDSCIDEYVTAYLIGGTTPPSGAKC