cmaA2 Resolved · high auto-curated
H37Rv Rv0503c · MTBC0 mtbc0_000531 ·
302 aa · 597212–598120 (-) ·
RefSeq NP_215017.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cyclopropane mycolic acid synthase |
|---|---|
| MTBC0 PGAP re-annotation | cyclopropane mycolic acid synthase CmaA2 |
| Revised (this work) | Cyclopropane mycolic acid synthase CmaA2. Pfam: CMAS (PF02353.27), Methyltransf_23 (PF13489.13), Methyltransf_12 (PF08242.19), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPB5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cyclopropane mycolic acid synthase 2 |
| EC (curated) |
EC 2.1.1.79
|
| Curated function | Catalyzes the formation of trans cyclopropanated ketomycolate or methoxymycolate through the conversion of a double bond to a cyclopropane ring at the proximal position of an oxygenated mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. In the absence of MmaA2, CmaA2 has a non-specific cis-cyclopropanating activity and is able to catalyze the conversion of a double bond to a cis cyclopropane ring at the distal position of an alpha mycolic acid. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and pers. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | cmaA2 |
| eggNOG description | synthase |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (93) |
GO:0001666, GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006629, GO:0006631 +81 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 | 0.116 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
CMAS | PF02353.27 | 1.3e-117 | 13–298 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 8.1e-09 | 67–195 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 4.1e-07 | 77–177 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 8.4e-07 | 77–158 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 2.0e-04 | 77–177 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: serB1 (phosphoserine phosphatase SerB), high confidence from genomic context alone (score 732 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0504c hyp |
hypothetical protein | 859 | 859 ctx | neighborhood:853 |
Rv0505c serB1 |
phosphoserine phosphatase SerB | 732 | 732 ctx | neighborhood:731 |
Rv0449c hyp |
hypothetical protein | 428 | 401 | |
Rv3800c pks13 |
polyketide synthase | 483 | 117 | textmining:439 |
Rv1527c pks5 |
polyketide synthase | 420 | 106 | |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 522 | 80 | textmining:502 |
Rv2246 kasB |
3-oxoacyl-ACP synthase 2 | 481 | 72 | textmining:464 |
Rv2245 kasA |
3-oxoacyl-ACP synthase 1 | 438 | 72 | textmining:420 |
Rv3801c fadD32 |
long-chain-fatty-acid--AMP ligase FadD32 | 552 | 60 | textmining:543 |
Rv1484 inhA |
NADH-dependent enoyl-[ACP | 402 | 52 | |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 445 | 48 | textmining:442 |
Rv3787c |
S-adenosyl-L-methionine-dependent methyltransferase | 433 | 41 | textmining:433 |
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: cyclopropane mycolic acid synthase
- MTBC0 PGAP product: cyclopropane mycolic acid synthase CmaA2
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=1e-117), Methyltransf_23 PF13489.13 (E=8e-09), Methyltransf_12 PF08242.19 (E=4e-07), Methyltransf_25 PF13649.13 (E=8e-07), Methyltransf_11 PF08241.19 (E=2e-04)
- (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_215017.1)
- Domains: Pfam-A via hmmscan --cut_ga — CMAS (PF02353.27), Methyltransf_23 (PF13489.13), Methyltransf_12 (PF08242.19), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19)
- 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
COG2230 - Curated reference: UniProt P9WPB5 (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 —
12 functional partner(s); context anchor
serB1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000531|Rv0503c|cmaA2 MTSQGDTTSGTQLKPPVEAVRSHYDKSNEFFKLWLDPSMTYSCAYFERPDMTLEEAQYAKRKLALDKLNLEPGMTLLDIGCGWGSTMRHAVAEYDVNVIGLTLSENQYAHDKAMFDEVDSPRRKEVRIQGWEEFDEPVDRIVSLGAFEHFADGAGDAGFERYDTFFKKFYNLTPDDGRMLLHTITIPDKEEAQELGLTSPMSLLRFIKFILTEIFPGGRLPRISQVDYYSSNAGWKVERYHRIGANYVPTLNAWADALQAHKDEAIALKGQETYDIYMHYLRGCSDLFRDKYTDVCQFTLVK