cyp136 Resolved · high auto-curated

H37Rv Rv3059 · MTBC0 mtbc0_003251 · 492 aa · 3440788–3442266 (+) · RefSeq NP_217575.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome P450 Cyp136
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 P9WPM7 SwissProt · reviewed · Evidence at protein level
UniProt namePutative cytochrome P450 136
EC (curated) EC 1.14.-.-

UniProt still lists this protein as Putative cytochrome P450 136; 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 namecyp136A2
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 0.391 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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 1.7e-6462–466 Cytochrome P450

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

Closest characterised functional partner: Rv3057c (short chain alcohol dehydrogenase/reductase), high confidence from genomic context alone (score 767 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3800c pks13 polyketide synthase 943 938 experimental:891
Rv2380c mbtE peptide synthetase 809 800 experimental:689
Rv1937 oxygenase 813 786 experimental:478
Rv3057c short chain alcohol dehydrogenase/reductase 767 767 ctx neighborhood:725
Rv3058c TetR family transcriptional regulator 755 754 ctx neighborhood:751
Rv1629 polA DNA polymerase I 709 690 database:638
Rv0719 rplF 50S ribosomal protein L6 690 690 experimental:412 database:493
Rv1777 cyp144 cytochrome P450 Cyp144 850 682 ctx cooccurence:680 textmining:550
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
Rv1527c pks5 polyketide synthase 693 660
Rv2940c mas multifunctional mycocerosic acid synthase 692 658
Rv2048c pks12 polyketide synthase 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 Cyp136
  • MTBC0 PGAP product: cytochrome P450
  • Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=2e-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_217575.1)
  • 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 P9WPM7 (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 — 121 functional partner(s); context anchor Rv3057c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003251|Rv3059|cyp136
MATIHPPAYLLDQAKRRFTPSFNNFPGMSLVEHMLLNTKFPEKKLAEPPPGSGLKPVVGDAGLPILGHMIEMLRGGPDYLMFLYKTKGPVVFGDSAVLPGVAALGPDAAQVIYSNRNKDYSQQGWVPVIGPFFHRGLMLLDFEEHMFHRRIMQEAFVRSRLAGYLEQMDRVVSRVVADDWVVNDARFLVYPAMKALTLDIASMVFMGHEPGTDHELVTKVNKAFTITTRAGNAVIRTSVPPFTWWRGLRARELLENYFTARVKERREASGNDLLTVLCQTEDDDGNRFSDADIVNHMIFLMMAAHDTSTSTATTMAYQLAAHPEWQQRCRDESDRHGDGPLDIESLEQLESLDLVMNESIRLVTPVQWAMRQTVRDTELLGYYLPKGTNVIAYPGMNHRLPEIWTDPLTFDPERFTEPRNEHKRHRYAFTPFGGGVHKCIGMVFGQLEIKTILHRLLRRYRLELSRPDYQPRWDYSAMPIPMDGMPIVLRPR