cyp142 Resolved · high auto-curated
H37Rv Rv3518c · MTBC0 mtbc0_003734 ·
398 aa · 3978002–3979198 (-) ·
RefSeq NP_218035.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cytochrome P450 monooxygenase Cyp142 |
|---|---|
| MTBC0 PGAP re-annotation | steroid C26-monooxygenase Cyp142 |
| Revised (this work) | Steroid C26-monooxygenase Cyp142. Pfam: p450 (PF00067.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPL5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Steroid C26-monooxygenase |
| EC (curated) |
EC 1.14.15.28
|
| 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 (25R)-26-hydroxycholest-4-en-3-one (alcohol), (25R)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25R)-3-oxocholest-4-en-26-oate. In vitro, Cyp142 catalyzes with equal preference the oxidation of both (25R)- and (25S)-26-hydroxycholest-4-en-3-one diastereomers to the corresponding carboxylic acid which is a prerequisite for entry into the beta-oxid. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | cyp142A3 |
| eggNOG description | cytochrome p450 |
| Orthologous group | COG2124 |
| EC number |
EC 1.14.13.221
|
| KEGG orthology |
K16046
|
| KEGG pathways |
map00984, map01120
|
| Gene Ontology (45) |
GO:0003674, GO:0003824, GO:0004497, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0006066, GO:0006629, GO:0006706, GO:0006707, GO:0008150 +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) pseudogene candidate
| pN/pS | 0.381 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 12.01% of strains (17434) · 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 |
|---|---|---|---|---|
p450 | PF00067.28 | 1.3e-23 | 163–360 | Cytochrome P450 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2776c (oxidoreductase), high confidence from genomic context alone (score 896 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 943 | 938 | experimental:891 |
Rv3545c cyp125 |
steroid C26-monooxygenase | 943 | 922 | database:900 |
Rv1106c |
3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase | 968 | 917 | database:900 textmining:633 |
Rv3409c choD |
cholesterol oxidase | 944 | 900 | database:900 textmining:471 |
Rv2776c |
oxidoreductase | 902 | 896 ctx | fusion:674 |
Rv2380c mbtE |
peptide synthetase | 809 | 800 | experimental:689 |
Rv3519 hyp |
hypothetical protein | 805 | 793 ctx | neighborhood:790 |
Rv1937 |
oxygenase | 814 | 787 | experimental:478 |
Rv0719 rplF |
50S ribosomal protein L6 | 690 | 691 | experimental:412 database:493 |
Rv1629 polA |
DNA polymerase I | 706 | 688 | database:638 |
Rv2946c pks1 |
polyketide synthase | 716 | 682 | experimental:460 |
Rv3554 fdxB |
electron transfer protein FdxB | 706 | 669 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 697 | 663 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 683 | 663 | experimental:460 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 695 | 662 |
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: cytochrome P450 monooxygenase Cyp142
- MTBC0 PGAP product: steroid C26-monooxygenase Cyp142
- Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=1e-23)
- (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_218035.1)
- 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 P9WPL5 (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 —
141 functional partner(s); context anchor
Rv2776c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003734|Rv3518c|cyp142 MTEAPDVDLADGNFYASREARAAYRWMRANQPVFRDRNGLAAASTYQAVIDAERQPELFSNAGGIRPDQPALPMMIDMDDPAHLLRRKLVNAGFTRKRVKDKEASIAALCDTLIDAVCERGECDFVRDLAAPLPMAVIGDMLGVRPEQRDMFLRWSDDLVTFLSSHVSQEDFQITMDAFAAYNDFTRATIAARRADPTDDLVSVLVSSEVDGERLSDDELVMETLLILIGGDETTRHTLSGGTEQLLRNRDQWDLLQRDPSLLPGAIEEMLRWTAPVKNMCRVLTADTEFHGTALCAGEKMMLLFESANFDEAVFCEPEKFDVQRNPNSHLAFGFGTHFCLGNQLARLELSLMTERVLRRLPDLRLVADDSVLPLRPANFVSGLESMPVVFTPSPPLG