papA3 Resolved · high auto-curated
H37Rv Rv1182 · MTBC0 mtbc0_001270 ·
472 aa · 1328477–1329895 (+) ·
RefSeq NP_215698.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyltransferase papA3 |
|---|---|
| MTBC0 PGAP re-annotation | acyltransferase PapA3 |
| Revised (this work) | Acyltransferase PapA3. Pfam: Condensation (PF00668.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIK5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Acyltransferase PapA3 |
| EC (curated) |
EC 2.3.1.278, EC 2.3.1.279
|
| Curated function | Involved in the biosynthesis of polyacyltrehalose (PAT), a pentaacylated, trehalose-based glycolipid that could have a role in anchoring the bacterial capsule. Catalyzes the sequential transfer of two palmitoyl groups onto a single glucose residue of trehalose generating the diacylated product 2,3-diacyltrehalose (trehalose dipalmitate). Although palmitoyl-CoA (PCoA) seems to be the physiological acyl donor, PapA3 can also use docosanoyl (22-carbon saturated fatty acid) coenzyme A as acyl donor. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | papA3 |
| eggNOG description | COG1020 Non-ribosomal peptide synthetase modules and related proteins |
| Orthologous group | COG1020 |
| Gene Ontology (31) |
GO:0003674, GO:0003824, GO:0005975, GO:0005984, GO:0005991, GO:0006629, GO:0006643, GO:0006664, GO:0008150, GO:0008152, GO:0008610, GO:0009058 +19 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 | 0.186 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 4 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 |
|---|---|---|---|---|
Condensation | PF00668.26 | 1.5e-18 | 54–468 | Condensation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks4 (polyketide beta-ketoacyl synthase), high confidence from genomic context alone (score 989 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 997 | 989 ctx | neighborhood:648 coexpression:917 experimental:473 textmining:786 |
Rv1183 mmpL10 |
transmembrane transport protein MmpL10 | 992 | 948 ctx | neighborhood:628 coexpression:806 textmining:858 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 963 | 927 ctx | neighborhood:513 coexpression:815 textmining:528 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 956 | 915 | coexpression:597 experimental:721 textmining:515 |
Rv1527c pks5 |
polyketide synthase | 903 | 888 | coexpression:466 experimental:721 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 912 | 886 | coexpression:469 experimental:721 |
Rv2048c pks12 |
polyketide synthase | 887 | 864 | coexpression:469 experimental:721 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 883 | 864 | coexpression:469 experimental:721 |
Rv3800c pks13 |
polyketide synthase | 891 | 858 | coexpression:661 experimental:473 |
Rv2377c mbtH hyp |
hypothetical protein | 761 | 747 | coexpression:424 experimental:564 |
Rv2946c pks1 |
polyketide synthase | 799 | 731 | coexpression:442 experimental:473 |
Rv1661 pks7 |
polyketide synthase | 754 | 725 | coexpression:443 experimental:473 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 749 | 722 | coexpression:443 experimental:473 |
Rv0210 hyp |
hypothetical protein | 716 | 717 ctx | cooccurence:715 |
Rv2383c mbtB |
phenyloxazoline synthase | 809 | 715 | coexpression:678 |
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: acyltransferase papA3
- MTBC0 PGAP product: acyltransferase PapA3
- Pfam (hmmscan --cut_ga): Condensation PF00668.26 (E=1e-18)
- (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_215698.1)
- Domains: Pfam-A via hmmscan --cut_ga — Condensation (PF00668.26)
- 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
COG1020 - Curated reference: UniProt P9WIK5 (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 —
112 functional partner(s); context anchor
pks4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001270|Rv1182|papA3 MLRVGPLTIGTLDDWAPSTGSTVSWRPSAVAHTKASQAPISDVPVSYMQAQHIRGYCEQKAKGLDYSRLMVVSCQQPGQCDIRAANYVINAHLRRHDTYRSWFQYNGNGQIIRRTIQDPADIEFVPVHHGELTLPQIREIVQNTPDPLQWGCFRFGIVQGCDHFTFFASVDHVHVDAMIVGVTLMEFHLMYAALVGGHAPLELPPAGSYDDFCRRQHTFSSTLTVESPQVRAWTKFAEGTNGSFPDFPLPLGDPSKPSDADIVTVMMLDEEQTAQFESVCTAAGARFIGGVLACCGLAEHELTGTTTYYGLTPRDTRRTPADAMTQGWFTGLIPITVPIAGSAFGDAARAAQTSFDSGVKLAEVPYDRVVELSSTLTMPRPNFPVVNFLDAGAAPLSVLLTAELTGTNIGVYSDGRYSYQLSIYVIRVEQGTAVAVMFPDNPIARESVARYLATLKSVFQRVAESGQQQNVA