pcaA Resolved · high auto-curated
H37Rv Rv0470c · MTBC0 - ·
287 aa · 560848–561711 (-) ·
RefSeq YP_177730.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cyclopropane mycolic acid synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Cyclopropane mycolic acid synthase. 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.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WPB3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cyclopropane mycolic acid synthase 3 |
| EC (curated) |
EC 2.1.1.79
|
| Curated function | Involved in the phagosome maturation block (PMB). Catalyzes the conversion of a double bond to a cyclopropane ring at the proximal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. It can use cis, cis 11,14-eicosadienoic acid and linoelaidic acid as substrate. 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 | pcaA |
| eggNOG description | synthase |
| Orthologous group | COG2230 |
| EC number |
EC 2.1.1.79
|
| KEGG orthology |
K00574
|
| Gene Ontology (85) |
GO:0003674, GO:0003824, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0006732, GO:0006790, GO:0008150, GO:0008152, GO:0008168, GO:0008610 +73 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 | 0.117 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 | 6.0e-119 | 5–283 | Mycolic acid cyclopropane synthetase |
Methyltransf_23 | PF13489.13 | 1.6e-09 | 51–224 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 3.8e-09 | 69–162 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 1.1e-05 | 69–165 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0472c (HTH-type transcriptional regulator), medium confidence from genomic context alone (score 500 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1411c lprG |
lipoprotein LprG | 533 | 533 | coexpression:533 |
Rv0470A hyp |
hypothetical protein | 514 | 515 ctx | neighborhood:500 |
Rv0471c hyp |
hypothetical protein | 506 | 506 ctx | neighborhood:491 |
Rv0472c |
HTH-type transcriptional regulator | 744 | 500 ctx | neighborhood:488 textmining:510 |
Rv0642c mmaA4 |
hydroxymycolate synthase MmaA4 | 474 | 461 | coexpression:441 |
Rv2954c hyp |
hypothetical protein | 435 | 429 | coexpression:420 |
Rv0475 hbhA |
heparin binding hemagglutinin HbhA | 415 | 222 | |
Rv3800c pks13 |
polyketide synthase | 485 | 119 | textmining:440 |
Rv2246 kasB |
3-oxoacyl-ACP synthase 2 | 601 | 84 | textmining:583 |
Rv2245 kasA |
3-oxoacyl-ACP synthase 1 | 514 | 81 | textmining:494 |
Rv0533c fabH |
3-oxoacyl-ACP synthase III | 485 | 73 | textmining:467 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 542 | 72 | textmining:527 |
Rv0824c desA1 |
acyl-ACP desaturase DesA | 460 | 69 | textmining:444 |
Rv1484 inhA |
NADH-dependent enoyl-[ACP | 410 | 68 | |
Rv3801c fadD32 |
long-chain-fatty-acid--AMP ligase FadD32 | 553 | 60 | textmining:544 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): cyclopropane mycolic acid synthase
- Pfam (hmmscan --cut_ga): CMAS PF02353.27 (E=6e-119), Methyltransf_23 PF13489.13 (E=2e-09), Methyltransf_25 PF13649.13 (E=4e-09), Methyltransf_11 PF08241.19 (E=1e-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 YP_177730.1)
- 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 P9WPB3 (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 —
18 functional partner(s); context anchor
Rv0472c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0470c|pcaA MSVQLTPHFGNVQAHYDLSDDFFRLFLDPTQTYSCAYFERDDMTLQEAQIAKIDLALGKLNLEPGMTLLDIGCGWGATMRRAIEKYDVNVVGLTLSENQAGHVQKMFDQMDTPRSRRVLLEGWEKFDEPVDRIVSIGAFEHFGHQRYHHFFEVTHRTLPADGKMLLHTIVRPTFKEGREKGLTLTHELVHFTKFILAEIFPGGWLPSIPTVHEYAEKVGFRVTAVQSLQLHYARTLDMWATALEANKDQAIAIQSQTVYDRYMKYLTGCAKLFRQGYTDVDQFTLEK