thiC Resolved · high auto-curated
H37Rv Rv0423c · MTBC0 mtbc0_000444 ·
547 aa · 511947–513590 (-) ·
RefSeq NP_214937.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phosphomethylpyrimidine synthase |
|---|---|
| MTBC0 PGAP re-annotation | phosphomethylpyrimidine synthase ThiC |
| Revised (this work) | Phosphomethylpyrimidine synthase ThiC. Pfam: ThiC-associated (PF13667.12), ThiC_Rad_SAM (PF01964.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WG79
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phosphomethylpyrimidine synthase |
| EC (curated) |
EC 4.1.99.17
|
| Curated function | Catalyzes the synthesis of the hydroxymethylpyrimidine phosphate (HMP-P) moiety of thiamine from aminoimidazole ribotide (AIR) in a radical S-adenosyl-L-methionine (SAM)-dependent reaction. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | thiC |
| eggNOG description | Catalyzes the synthesis of the hydroxymethylpyrimidine phosphate (HMP-P) moiety of thiamine from aminoimidazole ribotide (AIR) in a radical S-adenosyl-L-methionine (SAM)-dependent reaction |
| Orthologous group | COG0422 |
| EC number |
EC 4.1.99.17
|
| KEGG orthology |
K03147
|
| KEGG pathways |
map00730, map01100
|
| KEGG modules |
M00127
|
| Gene Ontology (46) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006725, GO:0006766, GO:0006767, GO:0006772, GO:0006790, GO:0006807 +34 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 | 0.641 · 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 |
|---|---|---|---|---|
ThiC-associated | PF13667.12 | 2.3e-08 | 15–72 | ThiC-associated domain |
ThiC_Rad_SAM | PF01964.25 | 1.8e-187 | 82–502 | Radical SAM ThiC family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: thiD (hydroxymethylpyrimidine/phosphomethylpyrimidine kinase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0422c thiD |
hydroxymethylpyrimidine/phosphomethylpyrimidine kinase | 998 | 997 ctx | neighborhood:846 coexpression:806 database:900 |
Rv0417 thiG |
thiazole synthase | 941 | 923 ctx | cooccurence:500 coexpression:816 |
Rv0414c thiE |
thiamine-phosphate synthase | 902 | 873 | coexpression:809 |
Rv0421c hyp |
hypothetical protein | 848 | 848 ctx | neighborhood:846 |
Rv0416 thiS |
sulfur carrier protein ThiS | 851 | 842 | coexpression:804 |
Rv1173 fbiC |
FO synthase | 859 | 817 | coexpression:802 |
Rv0809 purM |
phosphoribosylformylglycinamidine cyclo-ligase PurM | 814 | 803 | database:800 |
Rv3276c purK |
5-(carboxyamino)imidazole ribonucleotide synthase | 801 | 802 | database:800 |
Rv3116 moeB2 |
molybdenum cofactor biosynthesis protein MoeB | 664 | 542 | coexpression:480 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 664 | 542 | coexpression:480 |
Rv0424c hyp |
hypothetical protein | 518 | 518 ctx | neighborhood:506 |
Rv1589 bioB |
biotin synthetase | 641 | 507 | |
Rv2338c moeW |
molybdopterin biosynthesis protein MoeW | 527 | 492 | coexpression:475 |
Rv1355c moeY |
molybdopterin biosynthesis protein MoeY | 526 | 492 | coexpression:475 |
Rv2337c hyp |
hypothetical protein | 524 | 490 | coexpression:473 |
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: phosphomethylpyrimidine synthase
- MTBC0 PGAP product: phosphomethylpyrimidine synthase ThiC
- Pfam (hmmscan --cut_ga): ThiC-associated PF13667.12 (E=2e-08), ThiC_Rad_SAM PF01964.25 (E=2e-187)
- (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_214937.1)
- Domains: Pfam-A via hmmscan --cut_ga — ThiC-associated (PF13667.12), ThiC_Rad_SAM (PF01964.25)
- 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
COG0422 - Curated reference: UniProt P9WG79 (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 —
30 functional partner(s); context anchor
thiD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000444|Rv0423c|thiC MTITVEPSVTTGPIAGSAKAYREIEAPGSGATLQVPFRRVHLSTGDHFDLYDTSGPYTDTDTVIDLTAGLPHRPGVVRDRGTQLQRARAGEITAEMAFIAAREDMSAELVRDEVARGRAVIPANHHHPESEPMIIGKAFAVKVNANIGNSAVTSSIAEEVDKMVWATRWGADTIMDLSTGKNIHETREWILRNSPVPVGTVPIYQALEKVKGDPTELTWEIYRDTVIEQCEQGVDYMTVHAGVLLRYVPLTAKRVTGIVSRGGSIMAAWCLAHHRESFLYTNFEELCDIFARYDVTFSLGDGLRPGSIADANDAAQFAELRTLGELTKIAKAHGAQVMIEGPGHIPMHKIVENVRLEEELCEEAPFYTLGPLATDIAPAYDHITSAIGAAIIAQAGTAMLCYVTPKEHLGLPDRKDVKDGVIAYKIAAHAADLAKGHPRAQERDDALSTARFEFRWNDQFALSLDPDTAREFHDETLPAEPAKTAHFCSMCGPKFCSMRITQDVREYAAEHGLETEADIEAVLAAGMAEKSREFAEHGNRVYLPITQ