cyp121 Resolved · high auto-curated
H37Rv Rv2276 · MTBC0 mtbc0_002419 ·
396 aa · 2573854–2575044 (+) ·
RefSeq NP_216792.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cytochrome P450 Cyp121 |
|---|---|
| MTBC0 PGAP re-annotation | mycocyclosin synthase Cyp121 |
| Revised (this work) | Mycocyclosin synthase Cyp121. 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 |
P9WPP7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycocyclosin synthase |
| EC (curated) |
EC 1.14.19.70
|
| Curated function | Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | cyp121 |
| eggNOG description | Cytochrome P450 |
| Orthologous group | COG2124 |
| EC number |
EC 1.14.21.9
|
| KEGG orthology |
K17483
|
| Gene Ontology (28) |
GO:0003674, GO:0003824, GO:0005488, GO:0006629, GO:0008144, GO:0008150, GO:0008152, GO:0008202, GO:0009975, GO:0016125, GO:0016491, GO:0016705 +16 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 | 1.385 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.63% of strains (914) · 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 | 4.7e-15 | 216–364 | Cytochrome P450 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2275 (cyclo(L-tyrosyl-L-tyrosyl) synthase), high confidence from genomic context alone (score 991 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2275 |
cyclo(L-tyrosyl-L-tyrosyl) synthase | 996 | 991 ctx | neighborhood:881 coexpression:820 database:500 textmining:648 |
Rv3800c pks13 |
polyketide synthase | 948 | 938 | experimental:891 |
Rv1937 |
oxygenase | 834 | 811 | experimental:478 |
Rv2380c mbtE |
peptide synthetase | 810 | 801 | experimental:689 |
Rv2776c |
oxidoreductase | 750 | 735 | |
Rv0719 rplF |
50S ribosomal protein L6 | 698 | 699 | experimental:412 database:493 |
Rv3685c cyp137 |
cytochrome P450 Cyp137 | 843 | 694 ctx | cooccurence:694 textmining:511 |
Rv1629 polA |
DNA polymerase I | 729 | 688 | database:638 |
Rv2946c pks1 |
polyketide synthase | 718 | 684 | experimental:460 |
Rv3554 fdxB |
electron transfer protein FdxB | 705 | 668 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 686 | 666 | experimental:460 |
Rv2048c pks12 |
polyketide synthase | 697 | 663 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 696 | 663 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 696 | 662 | |
Rv1527c pks5 |
polyketide synthase | 695 | 661 |
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 Cyp121
- MTBC0 PGAP product: mycocyclosin synthase Cyp121
- Pfam (hmmscan --cut_ga): p450 PF00067.28 (E=5e-15)
- (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_216792.1)
- 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 P9WPP7 (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 —
129 functional partner(s); context anchor
Rv2275 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002419|Rv2276|cyp121 MTATVLLEVPFSARGDRIPDAVAELRTREPIRKVRTITGAEAWLVSSYALCTQVLEDRRFSMKETAAAGAPRLNALTVPPEVVNNMGNIADAGLRKAVMKAITPKAPGLEQFLRDTANSLLDNLITEGAPADLRNDFADPLATALHCKVLGIPQEDGPKLFRSLSIAFMSSADPIPAAKINWDRDIEYMAGILENPNITTGLMGELSRLRKDPAYSHVSDELFATIGVTFFGAGVISTGSFLTTALISLIQRPQLRNLLHEKPELIPAGVEELLRINLSFADGLPRLATADIQVGDVLVRKGELVLVLLEGANFDPEHFPNPGSIELDRPNPTSHLAFGRGQHFCPGSALGRRHAQIGIEALLKKMPGVDLAVPIDQLVWRTRFQRRIPERLPVLW