mmaA2 Resolved · high auto-curated
H37Rv Rv0644c · MTBC0 mtbc0_000682 ·
287 aa · 741850–742713 (-) ·
RefSeq NP_215158.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cyclopropane mycolic acid synthase CmaA |
|---|---|
| MTBC0 PGAP re-annotation | cyclopropane mycolic acid synthase MmaA2 |
| Revised (this work) | Cyclopropane mycolic acid synthase MmaA2. 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 |
Q79FX6
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cyclopropane mycolic acid synthase MmaA2 |
| EC (curated) |
EC 2.1.1.79
|
| Curated function | Catalyzes the conversion of a double bond to a cis cyclopropane ring at the distal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. MmaA2 also catalyzes the biosynthesis of the cis-cyclopropanated methoxymycolates. 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 | mmaA5 |
| eggNOG description | synthase |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (54) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152 +42 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 | 0.509 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
CMAS | PF02353.27 | 3.0e-124 | 5–283 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 1.0e-10 | 52–172 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 1.4e-10 | 69–162 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 3.0e-09 | 69–164 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 1.1e-08 | 69–165 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmaA3 (methoxy mycolic acid synthase MmaA3), medium confidence from genomic context alone (score 677 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1015c rplY |
50S ribosomal protein L25/general stress protein Ctc | 735 | 736 | coexpression:735 |
Rv0643c mmaA3 |
methoxy mycolic acid synthase MmaA3 | 681 | 677 ctx | neighborhood:496 |
Rv0642c mmaA4 |
hydroxymycolate synthase MmaA4 | 621 | 610 | |
Rv0449c hyp |
hypothetical protein | 539 | 518 ctx | fusion:424 |
Rv0645c mmaA1 |
mycolic acid methyltransferase MmaA1 | 530 | 509 ctx | neighborhood:483 |
Rv0646c lipG |
lipase/esterase LipG | 475 | 439 ctx | neighborhood:430 |
Rv0647c hyp |
hypothetical protein | 510 | 425 ctx | neighborhood:420 |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 424 | 139 | |
Rv0908 ctpE |
metal cation transporter ATPase E | 458 | 83 | textmining:434 |
Rv3787c |
S-adenosyl-L-methionine-dependent methyltransferase | 437 | 41 | textmining:437 |
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 MmaA2
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=3e-124), Methyltransf_23 PF13489.13 (E=1e-10), Methyltransf_25 PF13649.13 (E=1e-10), Methyltransf_12 PF08242.19 (E=3e-09), Methyltransf_11 PF08241.19 (E=1e-08)
- (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_215158.1)
- 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 Q79FX6 (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 —
10 functional partner(s); context anchor
mmaA3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000682|Rv0644c|mmaA2 MVNDLTPHFEDVQAHYDLSDDFFRLFLDPTQTYSCAHFEREDMTLEEAQIAKIDLALGKLGLQPGMTLLDIGCGWGATMRRAIAQYDVNVVGLTLSKNQAAHVQKSFDEMDTPRDRRVLLAGWEQFNEPVDRIVSIGAFEHFGHDRHADFFARAHKILPPDGVLLLHTITGLTRQQMVDHGLPLTLWLARFLKFIATEIFPGGQPPTIEMVEEQSAKTGFTLTRRQSLQPHYARTLDLWAEALQEHKSEAIAIQSEEVYERYMKYLTGCAKLFRVGYIDVNQFTLAK