Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | formyltetrahydrofolate deformylase |
| MTBC0 PGAP re-annotation | formyltetrahydrofolate deformylase |
| Revised (this work) | Formyltetrahydrofolate deformylase. Pfam: ACT (PF01842.32), Formyl_trans_N (PF00551.25). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHM3
SwissProt · reviewed
· Evidence at protein level
|
| UniProt name | Formyltetrahydrofolate deformylase |
| EC (curated) |
EC 3.5.1.10
|
| Curated function | Catalyzes the hydrolysis of 10-formyltetrahydrofolate (formyl-FH4) to formate and tetrahydrofolate (FH4). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
| Preferred name | purU |
| eggNOG description | Catalyzes the hydrolysis of 10-formyltetrahydrofolate (formyl-FH4) to formate and tetrahydrofolate (FH4) |
| Orthologous group | COG0788 |
| EC number |
EC 3.5.1.10
|
| KEGG orthology |
K01433
|
| KEGG pathways |
map00630, map00670
|
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, 5 missense, 0 nonsense, 1 frameshift
|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.12% of strains
(169) · clonal
|
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 |
ACT | PF01842.32 |
1.6e-10 | 33–92 |
ACT domain |
Formyl_trans_N | PF00551.25 |
3.4e-38 | 116–292 |
Formyl transferase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase |
974 |
941 |
database:900 textmining:593 |
Rv1093 glyA1 |
serine hydroxymethyltransferase |
943 |
916 |
database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase |
943 |
916 |
database:900 |
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN |
926 |
916 |
database:900 |
Rv2211c gcvT |
aminomethyltransferase |
930 |
909 |
database:900 |
Rv2124c metH |
methionine synthase |
914 |
907 |
database:900 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT |
920 |
904 |
database:900 |
Rv2763c dfrA |
dihydrofolate reductase |
916 |
904 |
database:900 |
Rv2754c thyX |
thymidylate synthase ThyX |
900 |
901 |
database:900 |
Rv1837c glcB |
malate synthase |
825 |
826 |
database:800 |
Rv2852c mqo |
malate:quinone oxidoreductase |
819 |
820 |
database:800 |
Rv1098c fum |
fumarate hydratase |
819 |
806 |
database:800 |
Rv1240 mdh |
malate dehydrogenase |
806 |
806 |
database:800 |
Rv2332 mez |
malate oxidoreductase |
805 |
805 |
database:800 |
Rv0211 pckA |
phosphoenolpyruvate carboxykinase |
805 |
801 |
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: formyltetrahydrofolate deformylase
- MTBC0 PGAP product: formyltetrahydrofolate deformylase
- Pfam (hmmscan --cut_ga): ACT PF01842.32 (E=2e-10), Formyl_trans_N PF00551.25 (E=3e-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 NP_217480.1)
- Domains: Pfam-A via hmmscan --cut_ga — ACT (PF01842.32), Formyl_trans_N (PF00551.25)
- 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
COG0788
- Curated reference: UniProt
P9WHM3
(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 —
33 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003147|Rv2964|purU
MGKGSMTAHATPNEPDYPPPPGGPPPPADIGRLLLRCHDRPGIIAAVSTFLARAGANIISLDQHSTAPEGGTFLQRAIFHLPGLTAAVDELQRDFGSTVADKFGIDYRFAEAAKPKRVAIMASTEDHCLLDLLWRNRRGELEMSVVMVIANHPDLAAHVRPFGVPFIHIPATRDTRTEAEQRQLQLLSGNVDLVVLARYMQILSPGFLEAIGCPLINIHHSFLPAFTGAAPYQRARERGVKLIGATAHYVTEVLDEGPIIEQDVVRVDHTHTVDDLVRVGADVERAVLSRAVLWHCQDRVIVHHNQTIVF
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