folP2 Resolved · high auto-curated
H37Rv Rv1207 · MTBC0 mtbc0_001295 ·
318 aa · 1359633–1360589 (+) ·
RefSeq NP_215723.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydropteroate synthase |
|---|---|
| MTBC0 PGAP re-annotation | dihydropteroate synthase |
| 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.
Curated reference (UniProt)
| UniProt |
P9WNC9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Inactive dihydropteroate synthase 2 |
| Curated function | Has very low affinity for the DHPS substrate 6-hydroxymethyl-7,8-dihydropterin-pyrophosphate, but can bind the inhibitor dapsone. Seems to lack dihydropteroate synthase activity, and does probably not function in folate metabolism. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | folP2 |
| 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 (8) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0044424, GO:0044444, GO:0044464
|
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 | 0.25 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
Pterin_bind | PF00809.29 | 7.2e-72 | 45–289 | Pterin binding enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folK (2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3606c folK |
2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase | 996 | 993 ctx | cooccurence:753 coexpression:731 database:900 textmining:518 |
Rv3607c folB |
dihydroneopterin aldolase | 992 | 986 ctx | cooccurence:470 coexpression:735 database:900 textmining:497 |
Rv2447c folC |
folylpolyglutamate synthase FolC | 993 | 985 ctx | fusion:603 coexpression:431 database:900 textmining:603 |
Rv3608c folP1 |
dihydropteroate synthase | 939 | 925 | database:900 |
Rv0812 |
4-amino-4-deoxychorismate lyase | 925 | 919 | database:900 |
Rv1208 gpgS |
glucosyl-3-phosphoglycerate synthase | 915 | 889 ctx | neighborhood:881 |
Rv3609c folE |
GTP cyclohydrolase I | 928 | 876 ctx | cooccurence:518 coexpression:733 textmining:445 |
Rv1210 tagA |
DNA-3-methyladenine glycosylase I TagA | 830 | 831 ctx | neighborhood:825 |
Rv1209 hyp |
hypothetical protein | 826 | 827 ctx | neighborhood:825 |
Rv1206 fadD6 |
fatty-acid--CoA ligase FadD6 | 798 | 798 ctx | neighborhood:796 |
Rv1205 log hyp |
hypothetical protein | 750 | 751 ctx | neighborhood:748 |
Rv0013 trpG |
anthranilate synthase component II | 602 | 562 | coexpression:419 |
Rv1211 hyp |
hypothetical protein | 551 | 550 ctx | neighborhood:549 |
Rv1005c pabB |
para-aminobenzoate synthase component I | 551 | 484 | |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 517 | 461 | coexpression:430 |
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: dihydropteroate synthase
- MTBC0 PGAP product: dihydropteroate synthase
- Pfam (hmmscan --cut_ga): Pterin_bind PF00809.29 (E=7e-72)
- (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_215723.1)
- 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 P9WNC9 (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 —
36 functional partner(s); context anchor
folK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001295|Rv1207|folP2 MRSTPPASAGRSTPPALAGHSTPPALAGHSTLCGRPVAGDRALIMAIVNRTPDSFYDKGATFSDAAARDAVHRAVADGADVIDVGGVKAGPGERVDVDTEITRLVPFIEWLRGAYPDQLISVDTWRAQVAKAACAAGADLINDTWGGVDPAMPEVAAEFGAGLVCAHTGGALPRTRPFRVSYGTTTRGVVDAVISQVTAAAERAVAAGVAREKVLIDPAHDFGKNTFHGLLLLRHVADLVMTGWPVLMALSNKDVVGETLGVDLTERLEGTLAATALAAAAGARMFRVHEVAATRRVLEMVASIQGVRPPTRTVRGLA