Rv3538 Resolved · high auto-curated
H37Rv Rv3538 · MTBC0 - ·
286 aa · 3977062–3977922 (+) ·
RefSeq YP_177986.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Dehydrogenase. 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.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
Q6MWW2
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Enoyl-CoA hydratase ChsH3 |
| EC (curated) |
EC 4.2.1.-
|
| Curated function | Degradation of the cholesterol side chain involves 3 multistep beta-oxidation cycles, this is involved in the second cycle. Hydrates bulky steroid enoyl-CoA esters, has highest activity with 3-OCDO-CoA (3-oxochol-4,22-dien-24-oyl-CoA) making (22S)-HOCO-CoA, followed by octenoyl-CoA, with weaker activity on 3-OCDS-CoA (3-oxocholest-4,24-dien-26-oyl-CoA) and none on 3-OPDC-CoA (3-oxo-pregna-4,17-diene-20- carboxyl-CoA). Hydrates the same substrate as EchA19, but the 2 enzymes make different stereoisomers of the product. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | hsd4B |
| 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 | 0.144 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 2 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 | 5.5e-20 | 18–147 | MFE-2 hydratase 2 N-terminal domain |
MaoC_dehydratas | PF01575.26 | 4.9e-26 | 163–269 | MaoC like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: kstD (3-oxosteroid 1-dehydrogenase), high confidence from genomic context alone (score 981 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 980 | 981 ctx | neighborhood:882 coexpression:818 |
Rv3548c |
short-chain type dehydrogenase/reductase | 962 | 963 ctx | fusion:900 cooccurence:478 |
Rv0148 |
short-chain type dehydrogenase/reductase | 956 | 956 ctx | fusion:900 |
Rv3502c |
3-oxoacyl-ACP reductase | 955 | 956 ctx | fusion:900 |
Rv1350 fabG2 |
3-oxoacyl-ACP reductase FabG | 932 | 932 ctx | fusion:900 |
Rv0242c fabG4 |
3-oxoacyl-ACP reductase FabG | 931 | 931 ctx | fusion:899 |
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 920 | 918 ctx | neighborhood:606 coexpression:659 database:436 |
Rv0769 |
oxidoreductase | 916 | 916 ctx | fusion:878 |
Rv3573c fadE34 |
acyl-CoA dehydrogenase FadE34 | 737 | 737 ctx | cooccurence:488 |
Rv3535c hsaG |
acetaldehyde dehydrogenase | 690 | 690 ctx | neighborhood:673 |
Rv3536c hsaE |
hydratase | 694 | 682 ctx | neighborhood:676 |
Rv3540c ltp2 |
lipid transfer protein | 759 | 680 ctx | cooccurence:481 |
Rv0687 |
NAD-dependent oxidoreductase | 668 | 667 ctx | fusion:514 |
Rv2790c ltp1 |
lipid-transfer protein | 673 | 661 ctx | cooccurence:458 |
Rv3562 fadE31 |
acyl-CoA dehydrogenase FadE31 | 793 | 649 | textmining:435 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): dehydrogenase
- Pfam (hmmscan --cut_ga): MFE-2_hydrat-2_N PF22622.3 (E=5e-20), MaoC_dehydratas PF01575.26 (E=5e-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 YP_177986.1)
- 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 Q6MWW2 (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 —
144 functional partner(s); context anchor
kstD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3538| MPIDLDVALGAQLPPVEFSWTSTDVQLYQLGLGAGSDPMNPRELSYLADDTPQVLPTFGNVAATFHLTTPPTVQFPGIDIELSKVLHASERVEVPAPLPPSGSARAVTRFTDIWDKGKAAVICSETTATTPDGLLLWTQKRSIYARGEGGFGGKRGPSGSDVAPERAPDLQVAMPILPQQALLYRLCGDRNPLHSDPEFAAAAGFPRPILHGLCTYGMTCKAIVDALLDSDATAVAGYGARFAGVAYPGETLTVNVWKDGRRLVASVVAPTRDNAVVLSGVELVPA