chsH2 Family assigned · medium auto-curated
H37Rv Rv3542c · MTBC0 mtbc0_003759 ·
311 aa · 4004722–4005657 (-) ·
RefSeq NP_218059.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | 3-oxo-23%2C24-bisnorchol-4%2C17(20)-dien-22-oyl-CoA hydratase subunit alpha ChsH2 |
| Revised (this work) | 3-oxo-23%2C24-bisnorchol-4%2C17(20)-dien-22-oyl-CoA hydratase subunit alpha ChsH2. Pfam: FAS1_DH_region (PF13452.12), OB_ChsH2_C (PF01796.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YGF8
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-oxo-4,17-pregnadiene-20-carboxyl-CoA hydratase alpha subunit |
| EC (curated) |
EC 4.2.1.-
|
| Curated function | Involved in cholesterol side chain degradation. Catalyzes the hydration of 3-oxo-4,17-pregnadiene-20-carboxyl-CoA (3-OPDC-CoA) to form 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA), in the modified beta-oxidation pathway for cholesterol side chain degradation. Can also use octenoyl-CoA and decenoyl-CoA, with lower efficiency. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | nucleic-acid-binding protein containing a Zn-ribbon |
| Orthologous group | COG1545 |
| KEGG orthology |
K07068
|
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 | 0.628 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 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 |
|---|---|---|---|---|
FAS1_DH_region | PF13452.12 | 3.5e-15 | 26–159 | FAS1-like, dehydratase domain region |
OB_ChsH2_C | PF01796.24 | 2.7e-20 | 234–295 | ChsH2, C-terminal OB-fold domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ltp2 (lipid transfer protein), high confidence from genomic context alone (score 999 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3541c chsH1 hyp |
hypothetical protein | 999 | 1000 ctx | neighborhood:882 fusion:798 cooccurence:774 coexpression:826 experimental:999 database:900 |
Rv3540c ltp2 |
lipid transfer protein | 999 | 999 ctx | neighborhood:882 cooccurence:761 coexpression:866 experimental:508 database:500 |
Rv3543c fadE29 |
acyl-CoA dehydrogenase FadE29 | 994 | 990 ctx | neighborhood:881 cooccurence:747 coexpression:421 database:500 textmining:478 |
Rv3544c fadE28 |
acyl-CoA dehydrogenase FadE28 | 980 | 980 ctx | neighborhood:881 cooccurence:674 database:500 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 964 | 943 ctx | neighborhood:778 coexpression:427 experimental:508 |
Rv3523 ltp3 |
lipid carrier protein | 953 | 924 ctx | cooccurence:740 coexpression:434 experimental:508 textmining:416 |
Rv3522 ltp4 |
lipid transfer protein | 940 | 920 ctx | cooccurence:770 coexpression:438 experimental:415 |
Rv3545c cyp125 |
steroid C26-monooxygenase | 916 | 910 ctx | neighborhood:866 |
Rv3574 kstR |
HTH-type transcriptional regulator KstR | 785 | 785 ctx | cooccurence:754 |
Rv3551 |
CoA-transferase subunit alpha | 778 | 778 ctx | cooccurence:768 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 778 | 778 ctx | cooccurence:766 |
Rv3552 |
CoA-transferase subunit beta | 778 | 778 ctx | cooccurence:768 |
Rv3521 hyp |
hypothetical protein | 784 | 774 ctx | cooccurence:773 |
Rv3568c hsaC |
extradiol dioxygenase | 763 | 761 ctx | cooccurence:756 |
Rv3504 fadE26 |
acyl-CoA dehydrogenase FadE26 | 754 | 753 ctx | cooccurence:743 |
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: hypothetical protein
- MTBC0 PGAP product: 3-oxo-23%2C24-bisnorchol-4%2C17(20)-dien-22-oyl-CoA hydratase subunit alpha ChsH2
- Pfam (hmmscan --cut_ga): FAS1_DH_region PF13452.12 (E=4e-15), OB_ChsH2_C PF01796.24 (E=3e-20)
- (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_218059.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAS1_DH_region (PF13452.12), OB_ChsH2_C (PF01796.24)
- 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
COG1545 - Curated reference: UniProt I6YGF8 (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 —
57 functional partner(s); context anchor
ltp2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003759|Rv3542c|chsH2 MTGVSDIQEAVAQIKAAGPSKPRLARDPVNQPMINNWVEAIGDRNPIYVDDAAARAAGHPGIVAPPAMIQVWTMMGLGGVRPKDDPLGPIIKLFDDAGYIGVVATNCEQTYHRYLLPGEQVSISAELGDVVGPKQTALGEGWFINQHIVWQVGDEDVAEMNWRILKFKPAGSPSSVPDDLDPDAMMRPSSSRDTAFFWDGVKAHELRIQRLADGSLRHPPVPAVWQDKSVPINYVVSSGRGTVFSFVVHHAPKVPGRTVPFVIALVELEEGVRMLGELRGADPARVAIGMPVRATYIDFPDWSLYAWEPDE