cyp51 Resolved · high auto-curated
H37Rv Rv0764c · MTBC0 mtbc0_000813 ·
451 aa · 861106–862461 (-) ·
RefSeq NP_215278.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lanosterol 14-alpha demethylase |
|---|---|
| MTBC0 PGAP re-annotation | lanosterol 14-alpha demethylase |
| Revised (this work) | Lanosterol 14-alpha demethylase. 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 |
P9WPP9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sterol 14alpha-demethylase |
| EC (curated) |
EC 1.14.15.36
|
| Curated function | Sterol 14alpha-demethylase whose physiological substrate is not known. Accepts electrons from the iron-sulfur ferredoxin Fdx encoded by an adjacent gene. In vitro, catalyzes C14-demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol, to produce the 8,14-dienes stereoselectively. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | cyp51 |
| eggNOG description | cytochrome p450 |
| Orthologous group | COG2124 |
| EC number |
EC 1.14.13.70
|
| KEGG orthology |
K05917
|
| KEGG pathways |
map00100, map01100, map01110, map01130
|
| KEGG modules |
M00101
|
| Gene Ontology (33) |
GO:0003674, GO:0003824, GO:0004497, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006629, GO:0008150, GO:0008152 +21 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 | 0.417 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 | 5.0e-64 | 17–440 | Cytochrome P450 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cyp123 (cytochrome P450 Cyp123), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0766c cyp123 |
cytochrome P450 Cyp123 | 999 | 994 ctx | neighborhood:882 cooccurence:690 coexpression:839 textmining:860 |
Rv0762c hyp |
hypothetical protein | 992 | 992 ctx | neighborhood:882 cooccurence:769 coexpression:744 |
Rv0763c |
ferredoxin | 990 | 990 ctx | neighborhood:882 cooccurence:592 coexpression:801 |
Rv0765c |
oxidoreductase | 989 | 989 ctx | neighborhood:882 cooccurence:406 coexpression:860 |
Rv0767c |
HTH-type transcriptional regulator | 968 | 968 ctx | neighborhood:881 cooccurence:730 |
Rv0770 |
oxidoreductase | 950 | 950 ctx | neighborhood:677 coexpression:801 |
Rv0771 |
4-carboxymuconolactone decarboxylase | 947 | 946 ctx | neighborhood:677 cooccurence:433 coexpression:730 |
Rv0768 aldA |
aldehyde dehydrogenase AldA | 943 | 943 ctx | neighborhood:758 coexpression:736 |
Rv3800c pks13 |
polyketide synthase | 943 | 938 | experimental:891 |
Rv2380c mbtE |
peptide synthetase | 810 | 801 | experimental:689 |
Rv0769 |
oxidoreductase | 798 | 798 ctx | neighborhood:731 |
Rv1937 |
oxygenase | 815 | 789 | experimental:478 |
Rv0761c adhB |
alcohol dehydrogenase B | 778 | 776 ctx | neighborhood:774 |
Rv0311 hyp |
hypothetical protein | 761 | 760 ctx | cooccurence:749 |
Rv0719 rplF |
50S ribosomal protein L6 | 690 | 690 | experimental:412 database:493 |
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: lanosterol 14-alpha demethylase
- MTBC0 PGAP product: lanosterol 14-alpha demethylase
- Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=5e-64)
- (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_215278.1)
- 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 P9WPP9 (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
cyp123 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000813|Rv0764c|cyp51 MSAVALPRVSGGHDEHGHLEEFRTDPIGLMQRVRDECGDVGTFQLAGKQVVLLSGSHANEFFFRAGDDDLDQAKAYPFMTPIFGEGVVFDASPERRKEMLHNAALRGEQMKGHAATIEDQVRRMIADWGEAGEIDLLDFFAELTIYTSSACLIGKKFRDQLDGRFAKLYHELERGTDPLAYVDPYLPIESFRRRDEARNGLVALVADIMNGRIANPPTDKSDRDMLDVLIAVKAETGTPRFSADEITGMFISMMFAGHHTSSGTASWTLIELMRHRDAYAAVIDELDELYGDGRSVSFHALRQIPQLENVLKETLRLHPPLIILMRVAKGEFEVQGHRIHEGDLVAASPAISNRIPEDFPDPHDFVPARYEQPRQEDLLNRWTWIPFGAGRHRCVGAAFAIMQIKAIFSVLLREYEFEMAQPPESYRNDHSKMVVQLAQPACVRYRRRTGV