dfrA Resolved · high auto-curated
H37Rv Rv2763c · MTBC0 mtbc0_002941 ·
159 aa · 3095545–3096024 (-) ·
RefSeq NP_217279.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydrofolate reductase |
|---|---|
| MTBC0 PGAP re-annotation | dihydrofolate reductase |
| Revised (this work) | Dihydrofolate reductase. Pfam: DHFR_1 (PF00186.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNX1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydrofolate reductase |
| EC (curated) |
EC 1.5.1.3
|
| Curated function | Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | folA |
| eggNOG description | Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis |
| Orthologous group | COG0262 |
| EC number |
EC 1.5.1.3
|
| KEGG orthology |
K00287
|
| KEGG pathways |
map00670, map00790, map01100, map01523
|
| KEGG modules |
M00126, M00840
|
| Gene Ontology (60) |
GO:0000166, GO:0003674, GO:0003824, GO:0004146, GO:0005488, GO:0006082, GO:0006575, GO:0006725, GO:0006730, GO:0006732, GO:0006760, GO:0006807 +48 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.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DHFR_1 | PF00186.25 | 9.1e-42 | 1–137 | Dihydrofolate reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thyA (thymidylate synthase ThyA), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2764c thyA |
thymidylate synthase ThyA | 999 | 998 ctx | neighborhood:793 cooccurence:774 coexpression:703 database:900 textmining:930 |
Rv2754c thyX |
thymidylate synthase ThyX | 997 | 960 ctx | neighborhood:611 database:900 textmining:936 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 921 | 911 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 920 | 910 | database:900 |
Rv1406 fmt |
methionyl-tRNA formyltransferase | 935 | 907 | database:900 |
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN | 926 | 905 | database:900 |
Rv2211c gcvT |
aminomethyltransferase | 925 | 905 | database:900 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 922 | 905 | database:900 |
Rv2124c metH |
methionine synthase | 927 | 904 | database:900 |
Rv2964 purU |
formyltetrahydrofolate deformylase | 916 | 904 | database:900 |
Rv2447c folC |
folylpolyglutamate synthase FolC | 991 | 900 | database:900 textmining:922 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT | 900 | 900 | database:900 |
Rv2762c hyp |
hypothetical protein | 937 | 827 ctx | neighborhood:791 textmining:651 |
Rv2492 hyp |
hypothetical protein | 749 | 715 | coexpression:699 |
Rv2765 |
hydrolase | 713 | 713 ctx | neighborhood:713 |
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: dihydrofolate reductase
- MTBC0 PGAP product: dihydrofolate reductase
- Pfam (hmmscan --cut_ga): DHFR_1 PF00186.25 (E=9e-42)
- (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_217279.1)
- Domains: Pfam-A via hmmscan --cut_ga — DHFR_1 (PF00186.25)
- 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
COG0262 - Curated reference: UniProt P9WNX1 (SwissProt, reviewed; Evidence at protein level)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
54 functional partner(s); context anchor
thyA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002941|Rv2763c|dfrA MVGLIWAQATSGVIGRGGDIPWRLPEDQAHFREITMGHTIVMGRRTWDSLPAKVRPLPGRRNVVLSRQADFMASGAEVVGSLEEALTSPETWVIGGGQVYALALPYATRCEVTEVDIGLPREAGDALAPVLDETWRGETGEWRFSRSGLRYRLYSYHRS