papA5 Resolved · high auto-curated
H37Rv Rv2939 · MTBC0 mtbc0_003122 ·
422 aa · 3295946–3297214 (+) ·
RefSeq NP_217455.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phthiocerol/phthiodiolone dimycocerosyl transferase |
|---|---|
| MTBC0 PGAP re-annotation | phthiocerol/phthiodiolone dimycocerosyl transferase |
| Revised (this work) | Phthiocerol/phthiodiolone dimycocerosyl transferase. Pfam: PapA_C (PF16911.11). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIN5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phthiocerol/phthiodiolone dimycocerosyl transferase |
| EC (curated) |
EC 2.3.1.282
|
| Curated function | Catalyzes diesterification of phthiocerol, phthiodiolone, and phenolphthiocerol with mycocerosic acids, the final step in the phthiocerol, phthiodiolone and phenolphthiocerol dimycocerosate esters (PDIM) synthesis. Can directly transfer the mycocerosate bound to the mycocerosic acid synthase (mas) onto the substrate alcohols. Is also able to catalyze acyl transfer using various nucleophiles as acceptors and several acyl-CoA thioesters as donors in vitro; preference is observed for saturated medium chain alcohols and long chain acyl-CoA thioesters. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | papA5 |
| eggNOG description | Catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosic acids, the final step in the phthiocerol and phthiodiolone dimycocerosate esters (PDIM) synthesis. Can directly transfer the mycocerosate bound to the mycocerosic acid synthase (mas) onto the substrate alcohols |
| Orthologous group | COG1020 |
| KEGG orthology |
K16023
|
| KEGG pathways |
map01051, map01052, map01130
|
| Gene Ontology (24) |
GO:0003674, GO:0003824, GO:0006629, GO:0008150, GO:0008152, GO:0008374, GO:0008610, GO:0009058, GO:0009273, GO:0009987, GO:0016043, GO:0016740 +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 | 0.344 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 6 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 |
|---|---|---|---|---|
PapA_C | PF16911.11 | 1.9e-63 | 208–393 | Phthiocerol/phthiodiolone dimycocerosyl transferase C-terminus |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: drrB (daunorubicin ABC transporter permease DrrB), high confidence from genomic context alone (score 968 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2937 drrB |
daunorubicin ABC transporter permease DrrB | 982 | 968 ctx | neighborhood:674 coexpression:855 textmining:465 |
Rv2938 drrC |
daunorubicin ABC transporter permease DrrC | 973 | 958 ctx | neighborhood:689 coexpression:839 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 991 | 954 ctx | neighborhood:622 cooccurence:436 coexpression:803 textmining:821 |
Rv2936 drrA |
daunorubicin ABC transporter ATP-binding protein DrrA | 983 | 947 ctx | neighborhood:668 coexpression:848 textmining:697 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 949 | 924 ctx | neighborhood:614 coexpression:733 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 907 | 826 ctx | neighborhood:656 coexpression:514 textmining:487 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 920 | 767 ctx | neighborhood:632 textmining:672 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 800 | 744 ctx | neighborhood:632 |
Rv2164c hyp |
hypothetical protein | 742 | 743 ctx | cooccurence:742 |
Rv3843c |
transmembrane protein | 741 | 741 ctx | cooccurence:741 |
Rv3903c cpnT hyp |
hypothetical protein | 734 | 735 ctx | cooccurence:732 |
Rv2945c lppX |
lipoprotein LppX | 785 | 731 ctx | cooccurence:587 |
Rv2948c fadD22 |
p-hydroxybenzoyl--AMP ligase | 760 | 730 | coexpression:730 |
Rv2423 hyp |
hypothetical protein | 718 | 718 ctx | cooccurence:718 |
Rv0538 |
membrane protein | 715 | 715 ctx | cooccurence:714 |
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: phthiocerol/phthiodiolone dimycocerosyl transferase
- MTBC0 PGAP product: phthiocerol/phthiodiolone dimycocerosyl transferase
- Pfam (hmmscan --cut_ga): PapA_C PF16911.11 (E=2e-63)
- (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_217455.1)
- Domains: Pfam-A via hmmscan --cut_ga — PapA_C (PF16911.11)
- 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 P9WIN5 (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 —
77 functional partner(s); context anchor
drrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003122|Rv2939|papA5 MFPGSVIRKLSHSEEVFAQYEVFTSMTIQLRGVIDVDALSDAFDALLETHPVLASHLEQSSDGGWNLVADDLLHSGICVIDGTAATNGSPSGNAELRLDQSVSLLHLQLILREGGAELTLYLHHCMADGHHGAVLVDELFSRYTDAVTTGDPGPITPQPTPLSMEAVLAQRGIRKQGLSGAERFMSVMYAYEIPATETPAVLAHPGLPQAVPVTRLWLSKQQTSDLMAFGREHRLSLNAVVAAAILLTEWQLRNTPHVPIPYVYPVDLRFVLAPPVAPTEATNLLGAASYLAEIGPNTDIVDLASDIVATLRADLANGVIQQSGLHFGTAFEGTPPGLPPLVFCTDATSFPTMRTPPGLEIEDIKGQFYCSISVPLDLYSCAVYAGQLIIEHHGHIAEPGKSLEAIRSLLCTVPSEYGWIME