cyp125 Resolved · high auto-curated
H37Rv Rv3545c · MTBC0 - ·
433 aa · 3984144–3985445 (-) ·
RefSeq NP_218062.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | steroid C26-monooxygenase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Steroid C26-monooxygenase. Pfam: p450 (PF00067.28). |
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 |
P9WPP1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Steroid C26-monooxygenase |
| EC (curated) |
EC 1.14.15.29
|
| Curated function | Involved in the utilization of cholesterol as the sole carbon and energy source by degrading the side chain during infection. Primarily catalyzes the sequential oxidation of the terminal methyl of cholest-4-en-3-one into (25S)-26-hydroxycholest-4-en-3-one (alcohol), (25S)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25S)-3-oxocholest-4-en-26-oate. Also able to sequentially oxidize cholesterol itself, not only cholest-4-en-3-one. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | cyp125 |
| eggNOG description | cytochrome p450 |
| Orthologous group | COG2124 |
| EC number |
EC 1.14.13.141
|
| KEGG orthology |
K15981
|
| KEGG pathways |
map00984, map01120
|
| Gene Ontology (45) |
GO:0003674, GO:0003824, GO:0004497, GO:0005488, GO:0006066, GO:0006629, GO:0006706, GO:0006707, GO:0008150, GO:0008152, GO:0008202, GO:0008203 +33 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 | 0.15 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 3 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 |
|---|---|---|---|---|
p450 | PF00067.28 | 2.2e-13 | 304–393 | Cytochrome P450 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE28 (acyl-CoA dehydrogenase FadE28), high confidence from genomic context alone (score 929 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 943 | 938 | experimental:891 |
Rv3544c fadE28 |
acyl-CoA dehydrogenase FadE28 | 987 | 929 ctx | neighborhood:882 textmining:833 |
Rv3518c cyp142 |
cytochrome P450 monooxygenase Cyp142 | 943 | 922 | database:900 |
Rv1106c |
3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase | 960 | 917 | database:900 textmining:546 |
Rv3543c fadE29 |
acyl-CoA dehydrogenase FadE29 | 983 | 916 ctx | neighborhood:882 textmining:816 |
Rv3542c chsH2 hyp |
hypothetical protein | 916 | 910 ctx | neighborhood:866 |
Rv3541c chsH1 hyp |
hypothetical protein | 968 | 907 ctx | neighborhood:863 textmining:672 |
Rv3409c choD |
cholesterol oxidase | 933 | 900 | database:900 |
Rv3540c ltp2 |
lipid transfer protein | 980 | 865 ctx | neighborhood:836 textmining:865 |
Rv3515c fadD19 |
acyl-CoA synthetase | 908 | 807 | database:670 textmining:546 |
Rv2380c mbtE |
peptide synthetase | 809 | 800 | experimental:689 |
Rv1937 |
oxygenase | 812 | 785 | experimental:478 |
Rv2776c |
oxidoreductase | 747 | 732 | |
Rv0719 rplF |
50S ribosomal protein L6 | 689 | 689 | experimental:412 database:493 |
Rv1629 polA |
DNA polymerase I | 706 | 687 | database:638 |
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): steroid C26-monooxygenase
- Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=2e-13)
- (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_218062.1)
- Domains: Pfam-A via hmmscan --cut_ga — p450 (PF00067.28)
- 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
COG2124 - Curated reference: UniProt P9WPP1 (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 —
140 functional partner(s); context anchor
fadE28 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3545c|cyp125 MSWNHQSVEIAVRRTTVPSPNLPPGFDFTDPAIYAERLPVAEFAELRSAAPIWWNGQDPGKGGGFHDGGFWAITKLNDVKEISRHSDVFSSYENGVIPRFKNDIAREDIEVQRFVMLNMDAPHHTRLRKIISRGFTPRAVGRLHDELQERAQKIAAEAAAAGSGDFVEQVSCELPLQAIAGLLGVPQEDRGKLFHWSNEMTGNEDPEYAHIDPKASSAELIGYAMKMAEEKAKNPADDIVTQLIQADIDGEKLSDDEFGFFVVMLAVAGNETTRNSITQGMMAFAEHPDQWELYKKVRPETAADEIVRWATPVTAFQRTALRDYELSGVQIKKGQRVVMFYRSANFDEEVFQDPFTFNILRNPNPHVGFGGTGAHYCIGANLARMTINLIFNAVADHMPDLKPISAPERLRSGWLNGIKHWQVDYTGRCPVAH