htdX Resolved · high auto-curated
H37Rv Rv0241c · MTBC0 mtbc0_000257 ·
280 aa · 290193–291035 (-) ·
RefSeq NP_214755.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-hydroxyacyl-thioester dehydratase HtdX |
|---|---|
| MTBC0 PGAP re-annotation | 3-hydroxyacyl-thioester dehydratase HtdX |
| Revised (this work) | 3-hydroxyacyl-thioester dehydratase HtdX. Pfam: MaoC_dehydratas (PF01575.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53664
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-hydroxyacyl-thioester dehydratase X |
| EC (curated) |
EC 4.2.1.-, EC 4.2.1.119, EC 4.2.1.55
|
| Curated function | Shows trans-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase activity. Displays a broad chain length specificity, with a predilection for the C8 to C12 substrates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| eggNOG description | dehydratase |
| Orthologous group | COG2030 |
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 | 0.549 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.22% of strains (321) · 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 |
|---|---|---|---|---|
MaoC_dehydratas | PF01575.26 | 1.1e-26 | 161–271 | MaoC like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fabG4 (3-oxoacyl-ACP reductase FabG), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0242c fabG4 |
3-oxoacyl-ACP reductase FabG | 998 | 997 ctx | neighborhood:879 cooccurence:768 coexpression:853 textmining:449 |
Rv0243 fadA2 |
acetyl-CoA acetyltransferase FadA | 993 | 993 ctx | neighborhood:772 cooccurence:749 coexpression:878 |
Rv0860 fadB |
fatty oxidation protein FadB | 737 | 721 | |
Rv3140 fadE23 |
acyl-CoA dehydrogenase FadE23 | 674 | 674 | |
Rv3139 fadE24 |
acyl-CoA dehydrogenase | 651 | 651 | |
Rv0672 fadE8 |
acyl-CoA dehydrogenase FadE8 | 648 | 648 | |
Rv3339c icd1 |
isocitrate dehydrogenase | 652 | 637 | database:476 |
Rv0154c fadE2 |
acyl-CoA dehydrogenase FadE2 | 579 | 578 | |
Rv1043c hyp |
hypothetical protein | 555 | 555 | database:498 |
Rv3363c hyp |
hypothetical protein | 553 | 553 | |
Rv0983 pepD |
serine protease PepD | 553 | 553 | database:498 |
Rv3671c marP |
serine protease | 552 | 553 | database:498 |
Rv0125 pepA |
serine protease PepA | 551 | 552 | database:498 |
Rv1223 htrA |
serine protease HtrA | 551 | 552 | database:498 |
Rv3229c desA3 |
stearoyl-CoA 9-desaturase | 527 | 526 ctx | cooccurence:515 |
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: 3-hydroxyacyl-thioester dehydratase HtdX
- MTBC0 PGAP product: 3-hydroxyacyl-thioester dehydratase HtdX
- Pfam (hmmscan --cut_ga): MaoC_dehydratas PF01575.26 (E=1e-26)
- (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_214755.1)
- Domains: Pfam-A via hmmscan --cut_ga — MaoC_dehydratas (PF01575.26)
- 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
COG2030 - Curated reference: UniProt O53664 (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 —
129 functional partner(s); context anchor
fabG4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000257|Rv0241c|htdX MTQPSGLKNLLRAAAGALPVVPRTDQLPNRTVTVEELPIDPANVAAYAAVTGLRYGNQVPLTYPFALTFPSVMSLVTGFDFPFAAMGAIHTENHITQYRPIAVTDAVGVRVRAENLREHRRGLLVDLVTNVSVGNDVAWHQVTTFLHQQRTSLSGEPKPPPQKKPKLPPPAAVLRITPAKIRRYAAVGGDHNPIHTNPIAAKLFGFPTVIAHGMFTAAAVLANIEARFPDAVRYSVRFAKPVLLPATAGLYVAEGDGGWDLTLRNMAKGYPHLTATVRGL