htdY Resolved · high auto-curated
H37Rv Rv3389c · MTBC0 mtbc0_003601 ·
290 aa · 3829358–3830230 (-) ·
RefSeq NP_217906.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-hydroxyacyl-thioester dehydratase HtdY |
|---|---|
| MTBC0 PGAP re-annotation | 3-hydroxyacyl-thioester dehydratase HtdY |
| Revised (this work) | 3-hydroxyacyl-thioester dehydratase HtdY. Pfam: MFE-2_hydrat-2_N (PF22622.3), 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 |
I6YBZ8
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-hydroxyacyl-thioester dehydratase Y |
| EC (curated) |
EC 4.2.1.-, EC 4.2.1.119
|
| Curated function | Shows trans-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase activity. In vitro, can hydrate various enoyl-CoA such as (2E)-hexenoyl-CoA, (2E)-octenoyl-CoA, (2E)-decenoyl-CoA, (2E)-dodecenoyl-CoA and (2E)-hexadecenoyl-CoA. May contribute to the persistence of the tuberculosis infection by inducing COX-2 expression in macrophages through MAPK-NF-kappaB signaling pathway. |
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 | 2.548 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 7 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 |
|---|---|---|---|---|
MFE-2_hydrat-2_N | PF22622.3 | 1.1e-23 | 17–143 | MFE-2 hydratase 2 N-terminal domain |
MaoC_dehydratas | PF01575.26 | 3.6e-33 | 161–272 | MaoC like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0148 (short-chain type dehydrogenase/reductase), high confidence from genomic context alone (score 970 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0148 |
short-chain type dehydrogenase/reductase | 970 | 970 ctx | fusion:900 cooccurence:583 |
Rv3548c |
short-chain type dehydrogenase/reductase | 958 | 959 ctx | fusion:900 cooccurence:422 |
Rv3502c |
3-oxoacyl-ACP reductase | 947 | 947 ctx | fusion:900 |
Rv0242c fabG4 |
3-oxoacyl-ACP reductase FabG | 951 | 931 ctx | fusion:900 |
Rv1350 fabG2 |
3-oxoacyl-ACP reductase FabG | 931 | 931 ctx | fusion:900 |
Rv0769 |
oxidoreductase | 931 | 930 ctx | fusion:899 |
Rv0687 |
NAD-dependent oxidoreductase | 882 | 882 ctx | fusion:828 |
Rv2790c ltp1 |
lipid-transfer protein | 709 | 698 ctx | cooccurence:517 |
Rv3559c |
oxidoreductase | 658 | 656 ctx | fusion:500 |
Rv3573c fadE34 |
acyl-CoA dehydrogenase FadE34 | 637 | 637 | |
Rv3390 lpqD |
lipoprotein LpqD | 634 | 635 ctx | neighborhood:632 |
Rv3339c icd1 |
isocitrate dehydrogenase | 645 | 632 | database:476 |
Rv3061c fadE22 |
acyl-CoA dehydrogenase FadE22 | 607 | 607 | |
Rv0271c fadE6 |
acyl-CoA dehydrogenase FadE6 | 600 | 600 | |
Rv3564 fadE33 |
acyl-CoA dehydrogenase FadE33 | 597 | 597 |
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 HtdY
- MTBC0 PGAP product: 3-hydroxyacyl-thioester dehydratase HtdY
- Pfam (hmmscan --cut_ga): MFE-2_hydrat-2_N PF22622.3 (E=1e-23), MaoC_dehydratas PF01575.26 (E=4e-33)
- (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_217906.1)
- Domains: Pfam-A via hmmscan --cut_ga — MFE-2_hydrat-2_N (PF22622.3), 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 I6YBZ8 (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 —
137 functional partner(s); context anchor
Rv0148 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003601|Rv3389c|htdY MAIDPNSIGAVTEPMLFEWTDRDTLLYAIGVGAGTGDLAFTTENSHGIDQQVLPTYAVICCPAFGAAAKVGTFNPAALLHGSQGIRLHAPLPAAGKLSVVTEVADIQDKGEGKNAIVVLRGRGCDPESGSLVAETLTTLVLRGQGGFGGARGERPAAPEFPDRHPDARIDMPTREDQALIYRLSGDRNPLHSDPWFATQLAGFPKPILHGLCTYGVAGRALVAELGGGVAANITSIAARFTKPVFPGETLSTVIWRTEPGRAVFRTEVAGSDGAEARVVLDDGAVEYVAG