folE Resolved · high auto-curated
H37Rv Rv3609c · MTBC0 mtbc0_003827 ·
202 aa · 4073681–4074289 (-) ·
RefSeq NP_218126.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GTP cyclohydrolase I |
|---|---|
| MTBC0 PGAP re-annotation | GTP cyclohydrolase I FolE |
| Revised (this work) | GTP cyclohydrolase I FolE. Pfam: GTP_cyclohydroI (PF01227.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN57
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GTP cyclohydrolase 1 |
| EC (curated) |
EC 3.5.4.16
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | folE |
| eggNOG description | GTP cyclohydrolase |
| Orthologous group | COG0302 |
| EC number |
EC 3.5.4.16
|
| KEGG orthology |
K01495
|
| KEGG pathways |
map00790, map01100
|
| KEGG modules |
M00126, M00841, M00842, M00843
|
| Gene Ontology (77) |
GO:0000166, GO:0001882, GO:0001883, GO:0003674, GO:0003824, GO:0003933, GO:0003934, GO:0005488, GO:0005525, GO:0005575, GO:0005622, GO:0005623 +65 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 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 |
|---|---|---|---|---|
GTP_cyclohydroI | PF01227.28 | 4.4e-76 | 22–199 | GTP cyclohydrolase I |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folP1 (dihydropteroate synthase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3608c folP1 |
dihydropteroate synthase | 999 | 998 ctx | neighborhood:881 fusion:460 cooccurence:539 coexpression:943 textmining:772 |
Rv3607c folB |
dihydroneopterin aldolase | 999 | 998 ctx | neighborhood:881 cooccurence:489 coexpression:967 textmining:862 |
Rv3606c folK |
2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase | 998 | 997 ctx | neighborhood:836 cooccurence:580 coexpression:957 textmining:586 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 976 | 974 ctx | neighborhood:867 coexpression:816 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 964 | 916 | database:900 textmining:593 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 972 | 908 | database:900 textmining:715 |
Rv0869c moaA2 |
molybdenum cofactor biosynthesis protein MoaA | 906 | 907 | database:900 |
Rv3109 moaA1 |
cyclic pyranopterin monophosphate synthase | 906 | 906 | database:900 |
Rv3605c hyp |
hypothetical protein | 887 | 887 ctx | neighborhood:881 |
Rv1207 folP2 |
dihydropteroate synthase | 928 | 876 ctx | cooccurence:518 coexpression:733 textmining:445 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 846 | 837 | database:800 |
Rv1617 pykA |
pyruvate kinase | 812 | 812 | database:800 |
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA | 816 | 809 | database:800 |
Rv3645 |
transmembrane protein | 808 | 808 | database:800 |
Rv1625c cya |
adenylate cyclase | 802 | 803 | database:800 |
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: GTP cyclohydrolase I
- MTBC0 PGAP product: GTP cyclohydrolase I FolE
- Pfam (hmmscan --cut_ga): GTP_cyclohydroI PF01227.28 (E=4e-76)
- (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_218126.1)
- Domains: Pfam-A via hmmscan --cut_ga — GTP_cyclohydroI (PF01227.28)
- 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
COG0302 - Curated reference: UniProt P9WN57 (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 —
67 functional partner(s); context anchor
folP1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003827|Rv3609c|folE MSQLDSRSASARIRVFDQQRAEAAVRELLYAIGEDPDRDGLVATPSRVARSYREMFAGLYTDPDSVLNTMFDEDHDELVLVKEIPMYSTCEHHLVAFHGVAHVGYIPGDDGRVTGLSKIARLVDLYAKRPQVQERLTSQIADALMKKLDPRGVIVVIEAEHLCMAMRGVRKPGSVTTTSAVRGLFKTNAASRAEALDLILRK