papA1 Resolved · high auto-curated
H37Rv Rv3824c · MTBC0 mtbc0_004053 ·
511 aa · 4315749–4317284 (-) ·
RefSeq NP_218341.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | acyltransferase PapA1 |
| Revised (this work) | Acyltransferase PapA1. 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 |
P9WIK9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2'-acyl-2-O-sulfo-trehalose |
| EC (curated) |
EC 2.3.1.283
|
| Curated function | Required for the biosynthesis of sulfolipid-1 (SL-1), a major mycobacterial cell wall lipid. Catalyzes the acylation of trehalose-2-sulfate-2'-palmitate (SL659) by adding the (hydroxy)phthioceranoyl group at the 3'-position to yield the diacylated intermediate 2-palmitoyl-3-(C43)-phthioceranyl-alpha, alpha'-D-trehalose-2'-sulfate (SL1278). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | papA1 |
| eggNOG description | COG1020 Non-ribosomal peptide synthetase modules and related proteins |
| Orthologous group | COG1020 |
| Gene Ontology (24) |
GO:0003674, GO:0003824, GO:0006082, GO:0006629, GO:0006790, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009987, GO:0016740, GO:0016746 +12 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 | 0.409 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 14 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.54% of strains (790) · clonal |
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 | 6.5e-15 | 71–385 | Condensation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks2 (phthioceranic/hydroxyphthioceranic acid synthase), high confidence from genomic context alone (score 991 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 998 | 991 ctx | neighborhood:665 coexpression:888 experimental:721 textmining:831 |
Rv3823c mmpL8 |
integral membrane transport protein MmpL8 | 994 | 937 ctx | neighborhood:535 coexpression:803 textmining:915 |
Rv1527c pks5 |
polyketide synthase | 905 | 889 | coexpression:466 experimental:721 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 911 | 887 | coexpression:468 experimental:721 |
Rv2048c pks12 |
polyketide synthase | 897 | 880 | coexpression:468 experimental:721 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 903 | 864 | coexpression:468 experimental:721 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 955 | 861 ctx | cooccurence:400 coexpression:551 experimental:473 textmining:690 |
Rv3800c pks13 |
polyketide synthase | 890 | 856 | coexpression:660 experimental:473 |
Rv2377c mbtH hyp |
hypothetical protein | 762 | 747 | coexpression:426 experimental:564 |
Rv2946c pks1 |
polyketide synthase | 799 | 731 | coexpression:441 experimental:473 |
Rv1661 pks7 |
polyketide synthase | 753 | 725 | coexpression:442 experimental:473 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 755 | 722 | coexpression:443 experimental:473 |
Rv2383c mbtB |
phenyloxazoline synthase | 797 | 716 | coexpression:680 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 790 | 704 | coexpression:442 experimental:473 |
Rv0405 pks6 |
membrane bound polyketide synthase | 719 | 703 | coexpression:440 experimental:473 |
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
- MTBC0 PGAP product: acyltransferase PapA1
- Pfam (hmmscan --cut_ga): Condensation PF00668.26 (E=6e-15)
- (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_218341.1)
- 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 P9WIK9 (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 —
110 functional partner(s); context anchor
pks2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004053|Rv3824c|papA1 MRIGPVELSAVKDWDPAPGVLVSWHPTPASCAKALAAPVSAVPPSYVQARQIRSFSEQAARGLDHSRLLIASVEVFGHCDLRAMTYVINAHLRRHDTYRSWFELRDTDHIVRHSIADPADIEFVPTTHGEMTSADLRQHIVATPDSLHWDCFSFGVIQRADSFTFYASIDHLHADGQFVGVGLMEFQSMYTALIMGEPPIGLSEAGSYVDFCVRQHEYTSALTVDSPEVRAWIDFAEINNGTFPEFPLPLGDPSVRCGGDLLSMMLMDEQQTQRFESACMAANARFIGGMLACIAIAIHELTGADTYFGITPKDIRTPADLMTQGWFTGQIPVTVPVAGLSFNEIARIAQTSFDTGADLAKVPFERVVELSPSLRRPQPLFSLVNFFDAQVGPLSAVTKLFEGLNVGTYSDGRVTYPLSTMVGRFDETAASVLFPDNPVARESVTAYLRAIRSVCMRIANGGTAERVGNVVALSPGRRNNIERMTWRSCRAGDFIDICNLKVANVTVDREA