cyp128 Resolved · high auto-curated
H37Rv Rv2268c · MTBC0 mtbc0_002410 ·
489 aa · 2568912–2570381 (-) ·
RefSeq NP_216784.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cytochrome P450 Cyp128 |
|---|---|
| MTBC0 PGAP re-annotation | cytochrome P450 |
| Revised (this work) | Cytochrome P450. 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 |
P9WPN7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Beta-dihydromenaquinone-9 omega-hydroxylase |
| EC (curated) |
EC 1.14.15.27
|
| Curated function | Involved in the biosynthesis of sulfomenaquinone (SMK, initially named S881 on the basis of its mass), which is localized in the outer envelope of M.tuberculosis and negatively regulates its virulence. Catalyzes the hydroxylation of beta-dihydromenaquinone-9, leading to the formation of omega-hydroxy-beta-dihydromenaquinone-9. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | cyp128 |
| eggNOG description | cytochrome p450 |
| Orthologous group | COG2124 |
| KEGG orthology |
K21199
|
| Gene Ontology (14) |
GO:0003674, GO:0003824, GO:0006629, GO:0008150, GO:0008152, GO:0008202, GO:0016125, GO:0016491, GO:0040007, GO:0044238, GO:0055114, GO:0071704 +2 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 | 0.539 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 9 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 6.74% of strains (9791) · 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 | 2.0e-19 | 304–455 | Cytochrome P450 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cyp139 (cytochrome P450 Cyp139), high confidence from genomic context alone (score 715 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2267c stf3 hyp |
hypothetical protein | 998 | 986 ctx | neighborhood:834 coexpression:821 database:500 textmining:875 |
Rv3800c pks13 |
polyketide synthase | 943 | 938 | experimental:891 |
Rv1937 |
oxygenase | 836 | 813 | experimental:478 |
Rv2380c mbtE |
peptide synthetase | 809 | 800 | experimental:689 |
Rv2269c hyp |
hypothetical protein | 968 | 767 ctx | neighborhood:765 textmining:870 |
Rv2776c |
oxidoreductase | 770 | 756 | |
Rv1666c cyp139 |
cytochrome P450 Cyp139 | 896 | 715 ctx | cooccurence:714 textmining:651 |
Rv1394c cyp132 |
cytochrome P450 Cyp132 | 860 | 703 ctx | cooccurence:700 textmining:548 |
Rv0719 rplF |
50S ribosomal protein L6 | 690 | 690 | experimental:412 database:493 |
Rv1629 polA |
DNA polymerase I | 705 | 687 | database:638 |
Rv2946c pks1 |
polyketide synthase | 715 | 680 | experimental:460 |
Rv3554 fdxB |
electron transfer protein FdxB | 705 | 668 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 681 | 661 | experimental:460 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 694 | 660 | |
Rv1527c pks5 |
polyketide synthase | 694 | 660 |
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 Cyp128
- MTBC0 PGAP product: cytochrome P450
- Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=2e-19)
- (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_216784.1)
- 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 P9WPN7 (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 —
120 functional partner(s); context anchor
cyp139 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002410|Rv2268c|cyp128 MTATQSPPEPAPDRVRLAGCPLAGTPDVGLTAQDATTALGVPTRRRASSGGIPVATSMWRDAQTVRTYGPAVAKALALRVAGKARSRLTGRHCRKFMQLTDFDPFDPAIAADPYPHYRELLAGERVQYNPKRDVYILSRYADVREAARNHDTLSSARGVTFSRGWLPFLPTSDPPAHTRMRKQLAPGMARGALETWRPMVDQLARELVGGLLTQTPADVVSTVAAPMPMRAITSVLGVDGPDEAAFCRLSNQAVRITDVALSASGLISLVQGFAGFRRLRALFTHRRDNGLLRECTVLGKLATHAEQGRLSDDELFFFAVLLLVAGYESTAHMISTLFLTLADYPDQLTLLAQQPDLIPSAIEEHLRFISPIQNICRTTRVDYSVGQAVIPAGSLVLLAWGAANRDPRQYEDPDVFRADRNPVGHLAFGSGIHLCPGTQLARMEGQAILREIVANIDRIEVVEPPTWTTNANLRGLTRLRVAVTPRVAP