folB Resolved · high auto-curated
H37Rv Rv3607c · MTBC0 - ·
133 aa · 4048744–4049145 (-) ·
RefSeq YP_177996.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydroneopterin aldolase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Dihydroneopterin aldolase. Pfam: FolB (PF02152.24). |
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 |
P9WNC5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydroneopterin aldolase |
| EC (curated) |
EC 1.13.11.81, EC 4.1.2.25, EC 5.1.99.8
|
| Curated function | Possible cargo protein of a type 1 encapsulin nanocompartment involved in protection against oxidative stress (Probable). Catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin, 7,8-dihydromonapterin and 7,8-dihydroxanthopterin, respectively, in equal quantities. After longer incubation times the only product is 6-hydroxymethyl-7,8-dihydropterin. Retains aldolase activity when encapsulated with a slight decrease in rate. It is not known if this protein is normally found in the encapsulin nanocompartment. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | folB |
| eggNOG description | Catalyzes the conversion of 7,8-dihydroneopterin to 6- hydroxymethyl-7,8-dihydropterin |
| Orthologous group | COG1539 |
| EC number |
EC 1.13.11.81, EC 2.7.6.3, EC 4.1.2.25, EC 5.1.99.8
|
| KEGG orthology |
K01633, K13940
|
| KEGG pathways |
map00790, map01100
|
| KEGG modules |
M00126, M00840
|
| Gene Ontology (2) |
GO:0008150, GO:0040007
|
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 | 0.178 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
FolB | PF02152.24 | 2.2e-38 | 5–116 | Dihydroneopterin aldolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folP1 (dihydropteroate synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3608c folP1 |
dihydropteroate synthase | 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 fusion:864 cooccurence:712 coexpression:974 database:900 textmining:718 |
Rv3609c folE |
GTP cyclohydrolase I | 999 | 998 ctx | neighborhood:881 cooccurence:489 coexpression:967 textmining:862 |
Rv1207 folP2 |
dihydropteroate synthase | 992 | 986 ctx | cooccurence:470 coexpression:735 database:900 textmining:497 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 963 | 962 ctx | neighborhood:867 coexpression:729 |
Rv3605c hyp |
hypothetical protein | 882 | 882 ctx | neighborhood:882 |
Rv3604c |
transmembrane protein | 738 | 738 ctx | neighborhood:734 |
Rv3602c panC |
pantothenate synthetase | 746 | 663 ctx | neighborhood:661 |
Rv3601c panD |
aspartate 1-decarboxylase | 677 | 663 ctx | neighborhood:661 |
Rv3600c coaX |
type III pantothenate kinase | 663 | 663 ctx | neighborhood:661 |
Rv3603c hyp |
hypothetical protein | 661 | 661 ctx | neighborhood:661 |
Rv3598c lysS |
lysine--tRNA ligase | 633 | 633 ctx | neighborhood:633 |
Rv3597c lsr2 |
iron-regulated H-NS-like protein | 596 | 596 ctx | neighborhood:593 |
Rv3611 |
Rv3611, (MTCY07H7B.11c), len: 217 aa. Hypothetical unknown arg-, pro-rich protein. Possible ORF containing several direct repeats. | 545 | 545 ctx | neighborhood:544 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 528 | 501 | coexpression:461 |
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): dihydroneopterin aldolase
- Pfam (hmmscan --cut_ga): FolB PF02152.24 (E=2e-38)
- (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_177996.1)
- Domains: Pfam-A via hmmscan --cut_ga — FolB (PF02152.24)
- 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
COG1539 - Curated reference: UniProt P9WNC5 (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
folP1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3607c|folB MADRIELRGLTVHGRHGVYDHERVAGQRFVIDVTVWIDLAEAANSDDLADTYDYVRLASRAAEIVAGPPRKLIETVGAEIADHVMDDQRVHAVEVAVHKPQAPIPQTFDDVAVVIRRSRRGGRGWVVPAGGAV