cmaA1 Resolved · high auto-curated
H37Rv Rv3392c · MTBC0 mtbc0_003604 ·
287 aa · 3833013–3833876 (-) ·
RefSeq NP_217909.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cyclopropane mycolic acid synthase CmaA |
|---|---|
| MTBC0 PGAP re-annotation | cyclopropane mycolic acid synthase CmaA1 |
| Revised (this work) | Cyclopropane mycolic acid synthase CmaA1. Pfam: CMAS (PF02353.27), Methyltransf_23 (PF13489.13), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), 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 |
P9WPB7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cyclopropane mycolic acid synthase 1 |
| EC (curated) |
EC 2.1.1.79
|
| Curated function | Catalyzes the conversion of a double bond to a cyclopropane ring at the distal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | cmaA1 |
| eggNOG description | synthase |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (57) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0006732, GO:0006790, GO:0008150 +45 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 | 0.148 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.16% of strains (234) · 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 |
|---|---|---|---|---|
CMAS | PF02353.27 | 3.2e-126 | 5–283 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 4.6e-09 | 52–181 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 1.6e-10 | 69–162 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 3.5e-08 | 69–163 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 1.2e-07 | 69–165 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: iunH (nucleoside hydrolase), medium confidence from genomic context alone (score 573 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0449c hyp |
hypothetical protein | 896 | 891 ctx | fusion:867 |
Rv3393 iunH |
nucleoside hydrolase | 573 | 573 ctx | neighborhood:567 |
Rv0448c hyp |
hypothetical protein | 491 | 471 | |
Rv3800c pks13 |
polyketide synthase | 409 | 108 | |
Rv2172c hyp |
hypothetical protein | 448 | 64 | textmining:435 |
Rv3254 hyp |
hypothetical protein | 451 | 61 | textmining:440 |
Rv1523 |
methyltransferase | 529 | 50 | textmining:525 |
Rv2171 lppM |
lipoprotein LppM | 525 | 47 | textmining:523 |
Rv0236A hyp |
hypothetical protein | 631 | 46 | textmining:630 |
Rv3305c amiA1 |
N-acyl-L-amino acid amidohydrolase AmiA | 443 | 46 | textmining:441 |
Rv3787c |
S-adenosyl-L-methionine-dependent methyltransferase | 630 | 42 | textmining:630 |
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 CmaA
- MTBC0 PGAP product: cyclopropane mycolic acid synthase CmaA1
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=3e-126), Methyltransf_23 PF13489.13 (E=5e-09), Methyltransf_25 PF13649.13 (E=2e-10), Methyltransf_12 PF08242.19 (E=4e-08), Methyltransf_11 PF08241.19 (E=1e-07)
- (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_217909.1)
- Domains: Pfam-A via hmmscan --cut_ga — CMAS (PF02353.27), Methyltransf_23 (PF13489.13), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), 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 P9WPB7 (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 —
11 functional partner(s); context anchor
iunH - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003604|Rv3392c|cmaA1 MPDELKPHFANVQAHYDLSDDFFRLFLDPTQTYSCAYFERDDMTLQEAQIAKIDLALGKLGLQPGMTLLDVGCGWGATMMRAVEKYDVNVVGLTLSKNQANHVQQLVANSESLRSKRVLLAGWEQFDEPVDRIVSIGAFEHFGHERYDAFFSLAHRLLPADGVMLLHTITGLHPKEIHERGLPMSFTFARFLKFIVTEIFPGGRLPSIPMVQECASANGFTVTRVQSLQPHYAKTLDLWSAALQANKGQAIALQSEEVYERYMKYLTGCAEMFRIGYIDVNQFTCQK