thiE Resolved · high auto-curated
H37Rv Rv0414c · MTBC0 mtbc0_000434 ·
222 aa · 503715–504383 (-) ·
RefSeq NP_214928.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | thiamine-phosphate synthase |
|---|---|
| MTBC0 PGAP re-annotation | thiamine phosphate synthase |
| Revised (this work) | Thiamine phosphate synthase. Pfam: TMP-TENI (PF02581.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG75
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Thiamine-phosphate synthase |
| EC (curated) |
EC 2.5.1.3
|
| Curated function | Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole monophosphate (THZ-P) and 2-methyl-4-amino-5-hydroxymethyl pyrimidine pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | thiE |
| eggNOG description | Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole monophosphate (THZ-P) and 2-methyl-4-amino-5-hydroxymethyl pyrimidine pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP) |
| Orthologous group | COG0352 |
| EC number |
EC 2.5.1.3
|
| KEGG orthology |
K00788
|
| KEGG pathways |
map00730, map01100
|
| KEGG modules |
M00127
|
| Gene Ontology (45) |
GO:0003674, GO:0003824, GO:0004789, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006725, GO:0006766, GO:0006767, GO:0006772, GO:0006790 +33 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 | 0.192 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
TMP-TENI | PF02581.24 | 1.7e-53 | 11–201 | Thiamine monophosphate synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thiD (hydroxymethylpyrimidine/phosphomethylpyrimidine kinase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0422c thiD |
hydroxymethylpyrimidine/phosphomethylpyrimidine kinase | 999 | 999 ctx | fusion:895 cooccurence:765 coexpression:742 database:900 textmining:595 |
Rv0417 thiG |
thiazole synthase | 994 | 990 ctx | neighborhood:774 cooccurence:735 coexpression:852 textmining:434 |
Rv0416 thiS |
sulfur carrier protein ThiS | 958 | 953 ctx | neighborhood:776 coexpression:798 |
Rv2977c thiL |
thiamine-monophosphate kinase | 944 | 908 | database:900 textmining:419 |
Rv3228 rsgA hyp |
hypothetical protein | 913 | 901 | database:900 |
Rv0423c thiC |
phosphomethylpyrimidine synthase | 902 | 873 | coexpression:809 |
Rv0415 thiO |
thiamine biosynthesis oxidoreductase ThiO | 888 | 873 ctx | neighborhood:776 cooccurence:412 |
Rv1173 fbiC |
FO synthase | 850 | 804 | coexpression:788 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 683 | 567 | coexpression:441 |
Rv1355c moeY |
molybdopterin biosynthesis protein MoeY | 576 | 542 | coexpression:441 |
Rv2338c moeW |
molybdopterin biosynthesis protein MoeW | 574 | 540 | coexpression:441 |
Rv3859c gltB |
glutamate synthase large subunit | 513 | 513 ctx | neighborhood:513 |
Rv3116 moeB2 |
molybdenum cofactor biosynthesis protein MoeB | 640 | 508 | coexpression:441 |
Rv2337c hyp |
hypothetical protein | 501 | 461 | coexpression:443 |
Rv0934 pstS1 |
phosphate ABC transporter substrate-binding lipoprotein PstS | 455 | 455 | coexpression:455 |
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: thiamine-phosphate synthase
- MTBC0 PGAP product: thiamine phosphate synthase
- Pfam (hmmscan --cut_ga): TMP-TENI PF02581.24 (E=2e-53)
- (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_214928.1)
- Domains: Pfam-A via hmmscan --cut_ga — TMP-TENI (PF02581.24)
- 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
COG0352 - Curated reference: UniProt P9WG75 (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 —
27 functional partner(s); context anchor
thiD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000434|Rv0414c|thiE MHESRLASARLYLCTDARRERGDLAQFAEAALAGGVDIIQLRDKGSPGELRFGPLQARDELAACEILADAAHRYGALFAVNDRADIARAAGADVLHLGQRDLPVNVARQILAPDTLIGRSTHDPDQVAAAAAGDADYFCVGPCWPTPTKPGRAAPGLGLVRVAAELGGDDKPWFAIGGINAQRLPAVLDAGARRIVVVRAITSADDPRAAAEQLRSALTAAN