cyp123 Resolved · high auto-curated

H37Rv Rv0766c · MTBC0 mtbc0_000815 · 402 aa · 863288–864496 (-) · RefSeq NP_215280.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome P450 Cyp123
MTBC0 PGAP re-annotationcytochrome 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 P9WPP5 SwissProt · reviewed · Evidence at protein level
UniProt namePutative cytochrome P450 123
EC (curated) EC 1.14.-.-

UniProt still lists this protein as Putative cytochrome P450 123; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namecyp123A3
eggNOG descriptioncytochrome p450
Orthologous groupCOG2124
Gene Ontology (38) GO:0003674, GO:0003824, GO:0004497, GO:0005575, GO:0005623, GO:0005886, GO:0006066, GO:0006629, GO:0006706, GO:0006707, GO:0008150, GO:0008152 +26 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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 7 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 7.67% of strains (11133) · 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)

PfamAccessioni-EvalueResiduesDescription
p450PF00067.28 2.9e-24205–372 Cytochrome P450

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: cyp51 (lanosterol 14-alpha demethylase), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0764c cyp51 lanosterol 14-alpha demethylase 999 994 ctx neighborhood:882 cooccurence:690 coexpression:839 textmining:860
Rv0765c oxidoreductase 982 983 ctx neighborhood:882 coexpression:836
Rv0768 aldA aldehyde dehydrogenase AldA 953 952 ctx neighborhood:758 coexpression:807
Rv0762c hyp hypothetical protein 952 952 ctx neighborhood:882 coexpression:431
Rv3800c pks13 polyketide synthase 943 938 experimental:891
Rv0763c ferredoxin 931 928 ctx neighborhood:882
Rv2776c oxidoreductase 920 916 ctx fusion:740
Rv0767c HTH-type transcriptional regulator 914 914 ctx neighborhood:881
Rv0770 oxidoreductase 895 895 ctx neighborhood:677 coexpression:687
Rv2380c mbtE peptide synthetase 809 800 experimental:689
Rv0769 oxidoreductase 795 795 ctx neighborhood:731
Rv1937 oxygenase 814 787 experimental:478
Rv0771 4-carboxymuconolactone decarboxylase 790 784 ctx neighborhood:677
Rv0761c adhB alcohol dehydrogenase B 778 776 ctx neighborhood:774
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 759 745 ctx neighborhood:522 database:485

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 Cyp123
  • MTBC0 PGAP product: cytochrome P450
  • Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=3e-24)
  • (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_215280.1)
  • 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 P9WPP5 (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 — 136 functional partner(s); context anchor cyp51
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000815|Rv0766c|cyp123
MTVRVGDPELVLDPYDYDFHEDPYPYYRRLRDEAPLYRNEERNFWAVSRHHDVLQGFRDSTALSNAYGVSLDPSSRTSEAYRVMSMLAMDDPAHLRMRTLVSKGFTPRRIRELEPQVLELARIHLDSALQTESFDFVAEFAGKLPMDVISELIGVPDTDRARIRALADAVLHREDGVADVPPPAMAASIELMRYYADLIAEFRRRPANNLTSALLAAELDGDRLSDQEIMAFLFLMVIAGNETTTKLLANAVYWAAHHPGQLARVFADHSRIPMWVEETLRYDTSSQILARTVAHDLTLYDTTIPEGEVLLLLPGSANRDDRVFDDPDDYRIGREIGCKLVSFGSGAHFCLGAHLARMEARVALGALLRRIRNYEVDDDNVVRVHSSNVRGFAHLPISVQAR