cyp138 Resolved · high auto-curated

H37Rv Rv0136 · MTBC0 mtbc0_000147 · 441 aa · 163712–165037 (+) · RefSeq NP_214650.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome P450 Cyp138
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 P9WPM3 SwissProt · reviewed · Evidence at protein level
UniProt namePutative cytochrome P450 138
EC (curated) EC 1.14.-.-

UniProt still lists this protein as Putative cytochrome P450 138; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namecyp138
eggNOG descriptioncytochrome P450
Orthologous groupCOG2124
Gene Ontology (13) GO:0003674, GO:0003824, GO:0006629, GO:0008150, GO:0008152, GO:0008202, GO:0016125, GO:0016491, GO:0044238, GO:0055114, GO:0071704, GO:1901360 +1 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 0.244 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 7 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)

PfamAccessioni-EvalueResiduesDescription
p450PF00067.28 9.3e-6141–416 Cytochrome P450

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

Closest characterised functional partner: Rv0135c (transcriptional regulator), high confidence from genomic context alone (score 863 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3800c pks13 polyketide synthase 943 938 experimental:891
Rv0135c transcriptional regulator 863 863 ctx neighborhood:778
Rv2380c mbtE peptide synthetase 810 801 experimental:689
Rv1937 oxygenase 823 797 experimental:478
Rv3554 fdxB electron transfer protein FdxB 742 709
Rv3571 kshB 3-ketosteroid-9-alpha-hydroxylase reductase subunit 777 703
Rv2776c oxidoreductase 708 691
Rv0719 rplF 50S ribosomal protein L6 690 690 experimental:412 database:493
Rv1629 polA DNA polymerase I 706 688 database:638
Rv2946c pks1 polyketide synthase 715 680 experimental:460
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 681 661 experimental:460
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 693 660
Rv1527c pks5 polyketide synthase 693 659
Rv2940c mas multifunctional mycocerosic acid synthase 693 659
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 692 658

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 Cyp138
  • MTBC0 PGAP product: cytochrome P450
  • Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=9e-61)
  • (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_214650.1)
  • 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 P9WPM3 (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 — 119 functional partner(s); context anchor Rv0135c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000147|Rv0136|cyp138
MSEVVTAAPAPPVVRLPPAVRGPKLFQGLAFVVSRRRLLGRFVRRYGKAFTANILMYGRVVVVADPQLARQVFTSSPEELGNIQPNLSRMFGSGSVFALDGDDHRRRRRLLAPPFHGKSMKNYETIIEEETLRETANWPQGQAFATLPSMMHITLNAILRAIFGAGGSELDELRRLIPPWVTLGSRLAALPKPKRDYGRLSPWGRLAEWRRQYDTVIDKLIEAERADPNFADRTDVLALMLRSTYDDGSIMSRKDIGDELLTLLAAGHETTAATLGWAFERLSRHPDVLAALVEEVDNGGHELRQAAILEVQRARTVIDFAARRVNPPVYQLGEWVIPRGYSIIINIAQIHGDPDVFPQPDRFDPQRYIGSKPSPFAWIPFGGGTRRCVGAAFANMEMDVVLRTVLRHFTLETTTAAGERSHGRGVAFTPKDGGRVVMRRR