mmaA4 Resolved · high auto-curated
H37Rv Rv0642c · MTBC0 mtbc0_000680 ·
301 aa · 739851–740756 (-) ·
RefSeq NP_215156.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hydroxymycolate synthase MmaA4 |
|---|---|
| MTBC0 PGAP re-annotation | hydroxymycolate synthase MmaA4 |
| Revised (this work) | Hydroxymycolate synthase MmaA4. 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 |
Q79FX8
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Hydroxymycolate synthase MmaA4 |
| EC (curated) |
EC 2.1.1.-
|
| Curated function | Involved in the biosynthesis of hydroxymycolate, a common precursor of oxygenated mycolic acids (methoxy-mycolate and keto-mycolate). Probably transfers a methyl group from the S-adenosylmethionine (SAM) cofactor and, subsequently or simultaneously, a water molecule onto the double bound of ethylene substrates, leading to the formation of the hydroxylated product at the distal position. Involved in the activation of the antitubercular drug thiacetazone (TAC). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | mmaA4 |
| eggNOG description | synthase |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (53) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152 +41 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 | 0.401 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 7 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 | 2.6e-120 | 13–290 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 1.6e-09 | 67–202 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 1.8e-09 | 78–171 | Methyltransferase domain |
Methyltransf_12 | PF08242.19 | 3.9e-07 | 78–172 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 7.8e-07 | 78–173 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmaA3 (methoxy mycolic acid synthase MmaA3), high confidence from genomic context alone (score 919 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0643c mmaA3 |
methoxy mycolic acid synthase MmaA3 | 920 | 919 ctx | neighborhood:589 coexpression:806 |
Rv0449c hyp |
hypothetical protein | 667 | 651 ctx | fusion:560 |
Rv0644c mmaA2 |
cyclopropane mycolic acid synthase CmaA | 621 | 610 | |
Rv0470c pcaA |
cyclopropane mycolic acid synthase | 474 | 461 | coexpression:441 |
Rv0635 hadA |
(3R)-hydroxyacyl-ACP dehydratase subunit HadA | 405 | 406 | |
Rv3800c pks13 |
polyketide synthase | 542 | 129 | textmining:496 |
Rv0892 |
monooxygenase | 546 | 47 | textmining:544 |
Rv1729c |
S-adenosylmethionine-dependent methyltransferase | 435 | 46 | 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: hydroxymycolate synthase MmaA4
- MTBC0 PGAP product: hydroxymycolate synthase MmaA4
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=3e-120), Methyltransf_23 PF13489.13 (E=2e-09), Methyltransf_25 PF13649.13 (E=2e-09), Methyltransf_12 PF08242.19 (E=4e-07), Methyltransf_11 PF08241.19 (E=8e-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_215156.1)
- 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 Q79FX8 (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 —
8 functional partner(s); context anchor
mmaA3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000680|Rv0642c|mmaA4 MTRMAEKPISPTKTRTRFEDIQAHYDVSDDFFALFQDPTRTYSCAYFEPPELTLEEAQYAKVDLNLDKLDLKPGMTLLDIGCGWGTTMRRAVERFDVNVIGLTLSKNQHARCEQVLASIDTNRSRQVLLQGWEDFAEPVDRIVSIEAFEHFGHENYDDFFKRCFNIMPADGRMTVQSSVSYHPYEMAARGKKLSFETARFIKFIVTEIFPGGRLPSTEMMVEHGEKAGFTVPEPLSLRPHYIKTLRIWGDTLQSNKDKAIEVTSEEVYNRYMKYLRGCEHYFTDEMLDCSLVTYLKPGAAA