folP1 Resolved · high auto-curated
H37Rv Rv3608c · MTBC0 - ·
280 aa · 4049138–4049980 (-) ·
RefSeq YP_177997.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydropteroate synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Dihydropteroate synthase. Pfam: Pterin_bind (PF00809.29). |
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 |
P9WND1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydropteroate synthase |
| EC (curated) |
EC 2.5.1.15
|
| Curated function | Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives..; FUNCTION: Is involved in the bioactivation of the antituberculous drug para-aminosalicylic acid (PAS). PAS is a close structural analog of pABA and acts as an alternative substrate for DHPS, leading to hydroxy-dihydropteroate (H2PtePAS). Metabolomic studies show that PAS, despite its in vitro activity as a competitive inhibitor of DHPS, does not inhibit growth of M.tuberculosis by inhibiting DH. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | folP |
| eggNOG description | Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives |
| Orthologous group | COG0294 |
| EC number |
EC 2.5.1.15
|
| KEGG orthology |
K00796
|
| KEGG pathways |
map00790, map01100
|
| KEGG modules |
M00126, M00841
|
| Gene Ontology (54) |
GO:0003674, GO:0003824, GO:0004156, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006575, GO:0006725, GO:0006732 +42 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 | 0.29 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
Pterin_bind | PF00809.29 | 7.7e-87 | 9–255 | Pterin binding enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folB (dihydroneopterin aldolase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3607c folB |
dihydroneopterin aldolase | 999 | 1000 ctx | neighborhood:882 cooccurence:455 coexpression:947 database:900 textmining:819 |
Rv3606c folK |
2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase | 999 | 1000 ctx | neighborhood:882 cooccurence:758 coexpression:945 database:900 textmining:571 |
Rv3609c folE |
GTP cyclohydrolase I | 999 | 998 ctx | neighborhood:881 fusion:460 cooccurence:539 coexpression:943 textmining:772 |
Rv2447c folC |
folylpolyglutamate synthase FolC | 999 | 994 ctx | fusion:840 coexpression:431 database:900 textmining:924 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 941 | 936 ctx | neighborhood:867 coexpression:539 |
Rv1207 folP2 |
dihydropteroate synthase | 939 | 925 | database:900 |
Rv0812 |
4-amino-4-deoxychorismate lyase | 926 | 919 | database:900 |
Rv3605c hyp |
hypothetical protein | 882 | 882 ctx | neighborhood:882 |
Rv2366c |
transmembrane protein | 793 | 793 | coexpression:793 |
Rv2365c hyp |
hypothetical protein | 753 | 754 | coexpression:746 |
Rv3602c panC |
pantothenate synthetase | 774 | 748 ctx | neighborhood:661 |
Rv1604 impA |
inositol-monophosphatase ImpA | 744 | 745 | coexpression:736 |
Rv3604c |
transmembrane protein | 736 | 737 ctx | neighborhood:734 |
Rv1634 |
multidrug-efflux transporter | 746 | 736 | coexpression:732 |
Rv3601c panD |
aspartate 1-decarboxylase | 679 | 663 ctx | neighborhood:661 |
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): dihydropteroate synthase
- Pfam (hmmscan --cut_ga): Pterin_bind PF00809.29 (E=8e-87)
- (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_177997.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pterin_bind (PF00809.29)
- 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
COG0294 - Curated reference: UniProt P9WND1 (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 —
58 functional partner(s); context anchor
folB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3608c|folP1 MSPAPVQVMGVLNVTDDSFSDGGCYLDLDDAVKHGLAMAAAGAGIVDVGGESSRPGATRVDPAVETSRVIPVVKELAAQGITVSIDTMRADVARAALQNGAQMVNDVSGGRADPAMGPLLAEADVPWVLMHWRAVSADTPHVPVRYGNVVAEVRADLLASVADAVAAGVDPARLVLDPGLGFAKTAQHNWAILHALPELVATGIPVLVGASRKRFLGALLAGPDGVMRPTDGRDTATAVISALAALHGAWGVRVHDVRASVDAIKVVEAWMGAERIERDG