mmaA1 Resolved · high auto-curated
H37Rv Rv0645c · MTBC0 mtbc0_000683 ·
286 aa · 742880–743740 (-) ·
RefSeq NP_215159.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mycolic acid methyltransferase MmaA1 |
|---|---|
| MTBC0 PGAP re-annotation | mycolic acid methyltransferase MmaA1 |
| Revised (this work) | Mycolic acid methyltransferase MmaA1. 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 |
P9WPB1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycolic acid methyltransferase MmaA1 |
| EC (curated) |
EC 2.1.1.-
|
| Curated function | Involved in the conversion of a cis-olefin into a trans-olefin with concomitant introduction of an allylic methyl branch at the proximal position of the precursor to both the methoxy and ketomycolic acids. It directly affects the cis- to trans ratio and indirectly affects the keto to methoxy ratio. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | mmaA1 |
| eggNOG description | synthase |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (48) |
GO:0003674, GO:0003824, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008168, GO:0008610, GO:0008757, GO:0008825 +36 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 | 0.05 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 1 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 | 3.6e-116 | 4–282 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 6.2e-09 | 53–223 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 2.4e-08 | 68–161 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 6.8e-05 | 68–164 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lipG (lipase/esterase LipG), medium confidence from genomic context alone (score 681 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0646c lipG |
lipase/esterase LipG | 848 | 681 ctx | neighborhood:675 textmining:543 |
Rv0647c hyp |
hypothetical protein | 881 | 667 ctx | neighborhood:664 textmining:658 |
Rv0449c hyp |
hypothetical protein | 584 | 565 ctx | fusion:466 |
Rv0644c mmaA2 |
cyclopropane mycolic acid synthase CmaA | 530 | 509 ctx | neighborhood:483 |
Rv0649 fabD2 |
malonyl CoA-acyl carrier protein transacylase | 470 | 470 ctx | neighborhood:470 |
Rv0650 |
sugar kinase | 464 | 464 ctx | neighborhood:463 |
Rv0648 |
alpha-mannosidase | 447 | 446 ctx | neighborhood:446 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 516 | 348 | |
Rv3254 hyp |
hypothetical protein | 424 | 61 | textmining:412 |
Rv3787c |
S-adenosyl-L-methionine-dependent methyltransferase | 547 | 44 | textmining:546 |
Rv3305c amiA1 |
N-acyl-L-amino acid amidohydrolase AmiA | 426 | 41 | textmining:427 |
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: mycolic acid methyltransferase MmaA1
- MTBC0 PGAP product: mycolic acid methyltransferase MmaA1
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=4e-116), Methyltransf_23 PF13489.13 (E=6e-09), Methyltransf_25 PF13649.13 (E=2e-08), Methyltransf_11 PF08241.19 (E=7e-05)
- (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_215159.1)
- 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 P9WPB1 (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
lipG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000683|Rv0645c|mmaA1 MAKLRPYYEESQSAYDISDDFFALFLDPTWVYTCAYFERDDMTLEEAQLAKVDLALDKLNLEPGMTLLDVGCGWGGALVRAVEKYDVNVIGLTLSRNHYERSKDRLAAIGTQRRAEARLQGWEEFEENVDRIVSFEAFDAFKKERYLTFFERSYDILPDDGRMLLHSLFTYDRRWLHEQGIALTMSDLRFLKFLRESIFPGGELPSEPDIVDNAQAAGFTIEHVQLLQQHYARTLDAWAANLQAARERAIAVQSEEVYNNFMHYLTGCAERFRRGLINVAQFTMTK