thrC Resolved · high auto-curated
H37Rv Rv1295 · MTBC0 mtbc0_001387 ·
360 aa · 1459736–1460818 (+) ·
RefSeq NP_215811.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | threonine synthase |
|---|---|
| MTBC0 PGAP re-annotation | threonine synthase |
| Revised (this work) | Threonine synthase. Pfam: PALP (PF00291.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG59
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Threonine synthase |
| EC (curated) |
EC 4.2.3.1
|
| Curated function | Catalyzes the gamma-elimination of phosphate from L-phosphohomoserine and the beta-addition of water to produce L-threonine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | thrC |
| eggNOG description | Catalyzes the gamma-elimination of phosphate from L- phosphohomoserine and the beta-addition of water to produce L- threonine |
| Orthologous group | COG0498 |
| EC number |
EC 4.2.3.1
|
| KEGG orthology |
K01733
|
| KEGG pathways |
map00260, map00750, map01100, map01110, map01120, map01230
|
| KEGG modules |
M00018
|
| Gene Ontology (57) |
GO:0003674, GO:0003824, GO:0004795, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006520 +45 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 | 0.437 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 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 |
|---|---|---|---|---|
PALP | PF00291.32 | 2.2e-72 | 32–327 | Pyridoxal-phosphate dependent enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thrB (homoserine kinase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1296 thrB |
homoserine kinase | 999 | 998 ctx | neighborhood:731 coexpression:920 database:900 textmining:709 |
Rv1294 thrA |
homoserine dehydrogenase | 999 | 996 ctx | neighborhood:881 coexpression:958 textmining:794 |
Rv1559 ilvA |
threonine dehydratase IlvA | 967 | 953 | coexpression:525 database:900 |
Rv0884c serC |
phosphoserine aminotransferase | 951 | 943 | database:900 |
Rv1292 argS |
arginine--tRNA ligase | 906 | 903 ctx | neighborhood:882 |
Rv1293 lysA |
diaminopimelate decarboxylase | 915 | 889 ctx | neighborhood:882 |
Rv3709c ask |
aspartokinase | 830 | 779 | coexpression:725 |
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 800 | 739 | coexpression:718 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 795 | 712 | coexpression:636 |
Rv2606c snzP |
pyridoxine biosynthesis protein | 724 | 661 | coexpression:655 |
Rv0069c sdaA |
L-serine dehydratase | 636 | 600 | database:500 |
Rv2996c serA1 |
D-3-phosphoglycerate dehydrogenase | 627 | 583 | coexpression:477 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 675 | 567 | coexpression:413 |
Rv3002c ilvN |
acetolactate synthase small subunit | 667 | 565 | coexpression:529 |
Rv0728c serA2 |
D-3-phosphoglycerate dehydrogenase SerA | 606 | 561 | coexpression:474 |
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: threonine synthase
- MTBC0 PGAP product: threonine synthase
- Pfam (hmmscan --cut_ga): PALP PF00291.32 (E=2e-72)
- (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_215811.1)
- Domains: Pfam-A via hmmscan --cut_ga — PALP (PF00291.32)
- 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
COG0498 - Curated reference: UniProt P9WG59 (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 —
59 functional partner(s); context anchor
thrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001387|Rv1295|thrC MTVPPTATHQPWPGVIAAYRDRLPVGDDWTPVTLLEGGTPLIAATNLSKQTGCTIHLKVEGLNPTGSFKDRGMTMAVTDALAHGQRAVLCASTGNTSASAAAYAARAGITCAVLIPQGKIAMGKLAQAVMHGAKIIQIDGNFDDCLELARKMAADFPTISLVNSVNPVRIEGQKTAAFEIVDVLGTAPDVHALPVGNAGNITAYWKGYTEYHQLGLIDKLPRMLGTQAAGAAPLVLGEPVSHPETIATAIRIGSPASWTSAVEAQQQSKGRFLAASDEEILAAYHLVARVEGVFVEPASAASIAGLLKAIDDGWVARGSTVVCTVTGNGLKDPDTALKDMPSVSPVPVDPVAVVEKLGLA