thyA Resolved · high auto-curated
H37Rv Rv2764c · MTBC0 - ·
263 aa · 3073680–3074471 (-) ·
RefSeq NP_217280.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | thymidylate synthase ThyA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Thymidylate synthase ThyA. Pfam: Thymidylat_synt (PF00303.25). |
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 |
P9WFR9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Thymidylate synthase ThyA |
| EC (curated) |
EC 2.1.1.45
|
| 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 reductant in the reaction, yielding dihydrofolate (DHF) as a by-product. This enzymatic reaction provides an intracellular de novo source of dTMP, an essential precursor for DNA biosynthesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | thyA |
| 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 reductant in the reaction, yielding dihydrofolate (DHF) as a by-product. This enzymatic reaction provides an intracellular de novo source of dTMP, an essential precursor for DNA biosynthesis |
| Orthologous group | COG0207 |
| EC number |
EC 2.1.1.45
|
| KEGG orthology |
K00560
|
| KEGG pathways |
map00240, map00670, map01100, map01523
|
| KEGG modules |
M00053
|
| Gene Ontology (90) |
GO:0003674, GO:0003824, GO:0004799, GO:0006139, GO:0006220, GO:0006221, GO:0006231, GO:0006244, GO:0006725, GO:0006753, GO:0006793, GO:0006796 +78 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 | 0.934 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 |
|---|---|---|---|---|
Thymidylat_synt | PF00303.25 | 2.1e-123 | 3–263 | Thymidylate synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dfrA (dihydrofolate reductase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2763c dfrA |
dihydrofolate reductase | 999 | 998 ctx | neighborhood:793 cooccurence:774 coexpression:703 database:900 textmining:930 |
Rv2754c thyX |
thymidylate synthase ThyX | 997 | 953 ctx | neighborhood:551 database:900 textmining:953 |
Rv2697c dut |
deoxyuridine 5'-triphosphate nucleotidohydrolase | 986 | 951 | coexpression:445 database:900 textmining:739 |
Rv3356c folD |
bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase | 965 | 924 | database:900 textmining:565 |
Rv3247c tmk |
thymidylate kinase | 940 | 918 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 942 | 909 | database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 942 | 908 | database:900 |
Rv2211c gcvT |
aminomethyltransferase | 928 | 905 | database:900 |
Rv3214 gpm2 |
phosphoglycerate mutase | 895 | 895 ctx | fusion:890 |
Rv2447c folC |
folylpolyglutamate synthase FolC | 985 | 801 | database:800 textmining:929 |
Rv2762c hyp |
hypothetical protein | 874 | 733 ctx | neighborhood:730 textmining:548 |
Rv2902c rnhB |
ribonuclease HII | 755 | 708 | coexpression:652 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 720 | 708 | coexpression:667 |
Rv3051c nrdE |
ribonucleoside-diphosphate reductase subunit alpha | 699 | 671 | coexpression:660 |
Rv0002 dnaN |
DNA polymerase III subunit beta | 713 | 658 | coexpression:602 |
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): thymidylate synthase ThyA
- Pfam (hmmscan --cut_ga): Thymidylat_synt PF00303.25 (E=2e-123)
- (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_217280.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thymidylat_synt (PF00303.25)
- 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
COG0207 - Curated reference: UniProt P9WFR9 (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 —
85 functional partner(s); context anchor
dfrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2764c|thyA MTPYEDLLRFVLETGTPKSDRTGTGTRSLFGQQMRYDLSAGFPLLTTKKVHFKSVAYELLWFLRGDSNIGWLHEHGVTIWDEWASDTGELGPIYGVQWRSWPAPSGEHIDQISAALDLLRTDPDSRRIIVSAWNVGEIERMALPPCHAFFQFYVADGRLSCQLYQRSADLFLGVPFNIASYALLTHMMAAQAGLSVGEFIWTGGDCHIYDNHVEQVRLQLSREPRPYPKLLLADRDSIFEYTYEDIVVKNYDPHPAIKAPVAV