mmaA3 Resolved · high auto-curated
H37Rv Rv0643c · MTBC0 mtbc0_000681 ·
293 aa · 740821–741702 (-) ·
RefSeq NP_215157.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | methoxy mycolic acid synthase MmaA3 |
|---|---|
| MTBC0 PGAP re-annotation | methoxy mycolic acid synthase MmaA3 |
| Revised (this work) | Methoxy mycolic acid synthase MmaA3. Pfam: CMAS (PF02353.27), Methyltransf_23 (PF13489.13), 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 |
P0CH91
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Methoxy mycolic acid synthase MmaA3 |
| EC (curated) |
EC 2.1.1.-
|
| Curated function | Involved in the biosynthesis of methoxymycolic acid. It catalyzes the O-methylation of the hydroxy group of the hydroxymycolate to form a methyl ether. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | mmaA3 |
| eggNOG description | Involved in the biosynthesis of methoxymycolic acid. It catalyzes the O-methylation of the hydroxy group of the hydroxymycolate to form a methyl ether |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (51) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008168 +39 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 | 0.293 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 | 2.0e-125 | 10–289 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 2.4e-08 | 65–229 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 8.5e-08 | 75–165 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 3.7e-06 | 75–171 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmaA4 (hydroxymycolate synthase MmaA4), high confidence from genomic context alone (score 919 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0642c mmaA4 |
hydroxymycolate synthase MmaA4 | 920 | 919 ctx | neighborhood:589 coexpression:806 |
Rv0644c mmaA2 |
cyclopropane mycolic acid synthase CmaA | 681 | 677 ctx | neighborhood:496 |
Rv0448c hyp |
hypothetical protein | 442 | 419 | |
Rv0449c hyp |
hypothetical protein | 429 | 403 | |
Rv0636 hadB |
(3R)-hydroxyacyl-ACP dehydratase subunit HadB | 593 | 289 | textmining:451 |
Rv3800c pks13 |
polyketide synthase | 443 | 120 | |
Rv2245 kasA |
3-oxoacyl-ACP synthase 1 | 421 | 68 | textmining:405 |
Rv0386 |
transcriptional regulator | 418 | 57 | textmining:409 |
Rv2488c |
LuxR family transcriptional regulator | 417 | 55 | textmining:409 |
Rv0373c |
carbon monoxyde dehydrogenase large subunit | 411 | 45 | textmining:409 |
Rv0195 |
two component transcriptional regulator | 408 | 41 | textmining:409 |
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: methoxy mycolic acid synthase MmaA3
- MTBC0 PGAP product: methoxy mycolic acid synthase MmaA3
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=2e-125), Methyltransf_23 PF13489.13 (E=2e-08), Methyltransf_25 PF13649.13 (E=8e-08), Methyltransf_11 PF08241.19 (E=4e-06)
- (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_215157.1)
- Domains: Pfam-A via hmmscan --cut_ga — CMAS (PF02353.27), Methyltransf_23 (PF13489.13), 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 P0CH91 (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
mmaA4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000681|Rv0643c|mmaA3 MSDNSTGTTKSRSNVDDVQAHYDLSDAFFALFQDPTRTYSCAYFERDDMTLHEAQVAKLDLTLGKLGLEPGMTLLDVGCGWGSVMKRAVERYDVNVVGLTLSKNQHAYCQQVLDKVDTNRSHRVLLSDWANFSEPVDRIVTIEAIEHFGFERYDDFFKFAYNAMPADGVMLLHSITGLHVKQVIERGIPLTMEMAKFIRFIVTDIFPGGRLPTIETIEEHVTKAGFTITDIQSLQPHFARTLDLWAEALQAHKDEAIEIQSAEVYERYMKYLTGCAKAFRMGYIDCNQFTLAK