Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cytochrome P450 Cyp124 |
|---|
| MTBC0 PGAP re-annotation | methyl-branched lipid omega-hydroxylase Cyp124 |
|---|
| Revised (this work) | Methyl-branched lipid omega-hydroxylase Cyp124. 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 |
P9WPP3
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Methyl-branched lipid omega-hydroxylase |
|---|
| EC (curated) |
EC 1.14.15.14, EC 1.14.15.28
|
|---|
| Curated function | Primarily hydroxylates the omega-carbon of a number of methyl-branched lipids, including (2E,6E)-farnesol, phytanate, geranylgeraniol, 15-methylpalmitate and (2E,6E)-farnesyl diphosphate. Also 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. Cyp124 catalyzes preferentially the oxidation of (25R)-26-hydroxycholest-4-en-3-one diastereomer. Also able to sequentially oxidize cholesterol itself, not only ch. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|
| Preferred name | cyp124A1 |
|---|
| eggNOG description | cytochrome p450 |
|---|
| Orthologous group | COG2124 |
|---|
| EC number |
EC 1.14.15.14
|
|---|
| KEGG orthology |
K20497
|
|---|
| Gene Ontology (60) |
GO:0000166, GO:0003674, GO:0003824, GO:0004497, GO:0005488, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006706, GO:0006707, GO:0008150 +48 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 |
2.925 · diversifying/relaxed
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 9 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 |
1.3e-12 | 303–393 |
Cytochrome P450 |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3800c pks13 |
polyketide synthase |
943 |
938 |
experimental:891 |
Rv2380c mbtE |
peptide synthetase |
809 |
800 |
experimental:689 |
Rv1937 |
oxygenase |
812 |
785 |
experimental:478 |
Rv2776c |
oxidoreductase |
796 |
783 |
|
Rv0719 rplF |
50S ribosomal protein L6 |
689 |
689 |
experimental:412 database:493 |
Rv1629 polA |
DNA polymerase I |
704 |
686 |
database:638 |
Rv2946c pks1 |
polyketide synthase |
715 |
680 |
experimental:460 |
Rv3554 fdxB |
electron transfer protein FdxB |
703 |
666 |
|
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB |
681 |
661 |
experimental:460 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase |
694 |
660 |
|
Rv2940c mas |
multifunctional mycocerosic acid synthase |
692 |
658 |
|
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC |
692 |
658 |
|
Rv1527c pks5 |
polyketide synthase |
692 |
658 |
|
Rv2048c pks12 |
polyketide synthase |
692 |
658 |
|
Rv3230c |
stearoyl-CoA 9-desaturase electron transfer protein |
665 |
645 |
|
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 Cyp124
- MTBC0 PGAP product: methyl-branched lipid omega-hydroxylase Cyp124
- Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=1e-12)
- (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_216782.1)
- 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
P9WPP3
(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 —
130 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002408|Rv2266|cyp124
MGLNTAIATRVNGTPPPEVPIADIELGSLDFWALDDDVRDGAFATLRREAPISFWPTIELPGFVAGNGHWALTKYDDVFYASRHPDIFSSYPNITINDQTPELAEYFGSMIVLDDPRHQRLRSIVSRAFTPKVVARIEAAVRDRAHRLVSSMIANNPDRQADLVSELAGPLPLQIICDMMGIPKADHQRIFHWTNVILGFGDPDLATDFDEFMQVSADIGAYATALAEDRRVNHHDDLTSSLVEAEVDGERLSSREIASFFILLVVAGNETTRNAITHGVLALSRYPEQRDRWWSDFDGLAPTAVEEIVRWASPVVYMRRTLTQDIELRGTKMAAGDKVSLWYCSANRDESKFADPWTFDLARNPNPHLGFGGGGAHFCLGANLARREIRVAFDELRRQMPDVVATEEPARLLSQFIHGIKTLPVTWS
Spot an error? Suggest an improvement