thyX Resolved · high auto-curated
H37Rv Rv2754c · MTBC0 mtbc0_002931 ·
250 aa · 3089608–3090360 (-) ·
RefSeq NP_217270.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | thymidylate synthase ThyX |
|---|---|
| MTBC0 PGAP re-annotation | FAD-dependent thymidylate synthase |
| Revised (this work) | FAD-dependent thymidylate synthase. Pfam: Thy1 (PF02511.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG57
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Flavin-dependent thymidylate synthase |
| EC (curated) |
EC 2.1.1.148
|
| Curated function | Catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor, and NADPH and FADH(2) as the reductant. Is essential for growth of the pathogen on solid media in vitro; the essential function is something other than dTMP synthase. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | thyX |
| eggNOG description | Catalyzes the reductive methylation of 2'-deoxyuridine- 5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor, and NADPH and FADH(2) as the reductant |
| Orthologous group | COG1351 |
| EC number |
EC 2.1.1.148
|
| KEGG orthology |
K03465
|
| KEGG pathways |
map00240, map00670, map01100
|
| Gene Ontology (25) |
GO:0000166, GO:0003674, GO:0003824, GO:0004799, GO:0005488, GO:0008150, GO:0008152, GO:0008168, GO:0016740, GO:0016741, GO:0032259, GO:0036094 +13 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 | 0.692 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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 |
|---|---|---|---|---|
Thy1 | PF02511.21 | 1.4e-61 | 31–224 | Thymidylate synthase complementing protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dfrA (dihydrofolate reductase), high confidence from genomic context alone (score 960 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2763c dfrA |
dihydrofolate reductase | 997 | 960 ctx | neighborhood:611 database:900 textmining:936 |
Rv2764c thyA |
thymidylate synthase ThyA | 997 | 953 ctx | neighborhood:551 database:900 textmining:953 |
Rv3247c tmk |
thymidylate kinase | 932 | 921 | database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 940 | 919 | database:900 |
Rv0956 purN |
phosphoribosylglycinamide formyltransferase PurN | 943 | 918 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 939 | 918 | database:900 |
Rv2697c dut |
deoxyuridine 5'-triphosphate nucleotidohydrolase | 993 | 908 | database:900 textmining:934 |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase | 948 | 908 | database:900 textmining:458 |
Rv2124c metH |
methionine synthase | 931 | 903 | database:900 |
Rv1406 fmt |
methionyl-tRNA formyltransferase | 944 | 902 | database:900 textmining:463 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 925 | 902 | database:900 |
Rv2211c gcvT |
aminomethyltransferase | 915 | 901 | database:900 |
Rv2964 purU |
formyltetrahydrofolate deformylase | 900 | 901 | database:900 |
Rv0389 purT |
phosphoribosylglycinamide formyltransferase PurT | 900 | 900 | database:900 |
Rv2753c dapA |
4-hydroxy-tetrahydrodipicolinate synthase | 861 | 822 ctx | neighborhood:795 |
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: thymidylate synthase ThyX
- MTBC0 PGAP product: FAD-dependent thymidylate synthase
- Pfam (hmmscan --cut_ga): Thy1 PF02511.21 (E=1e-61)
- (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_217270.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thy1 (PF02511.21)
- 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
COG1351 - Curated reference: UniProt P9WG57 (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 —
38 functional partner(s); context anchor
dfrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002931|Rv2754c|thyX MAETAPLRVQLIAKTDFLAPPDVPWTTDADGGPALVEFAGRACYQSWSKPNPKTATNAGYLRHIIDVGHFSVLEHASVSFYITGISRSCTHELIRHRHFSYSQLSQRYVPEKDSRVVVPPGMEDDADLRHILTEAADAARATYSELLAKLEAKFADQPNAILRRKQARQAARAVLPNATETRIVVTGNYRAWRHFIAMRASEHADVEIRRLAIECLRQLAAVAPAVFADFEVTTLADGTEVATSPLATEA