thiG Resolved · high auto-curated

H37Rv Rv0417 · MTBC0 mtbc0_000437 · 252 aa · 505731–506489 (+) · RefSeq NP_214931.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)thiazole synthase
MTBC0 PGAP re-annotationthiazole synthase
Revised (this work)Thiazole synthase. Pfam: ThiG (PF05690.21).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WG73 SwissProt · reviewed · Evidence at protein level
UniProt nameThiazole synthase
EC (curated) EC 2.8.1.10
Curated functionCatalyzes the rearrangement of 1-deoxy-D-xylulose 5-phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. Sulfur is provided by the thiocarboxylate moiety of the carrier protein ThiS. In vitro, sulfur can be provided by H(2)S.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namethiG
eggNOG descriptionCatalyzes the rearrangement of 1-deoxy-D-xylulose 5- phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. Sulfur is provided by the thiocarboxylate moiety of the carrier protein ThiS. In vitro, sulfur can be provided by H(2)S
Orthologous groupCOG2022
EC number EC 2.8.1.10
KEGG orthology K03149
KEGG pathways map00730, map01100
Gene Ontology (2) GO:0008150, GO:0040007

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 0.757 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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)

PfamAccessioni-EvalueResiduesDescription
ThiGPF05690.21 8.6e-1088–250 Thiazole biosynthesis protein ThiG

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: thiO (thiamine biosynthesis oxidoreductase ThiO), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0415 thiO thiamine biosynthesis oxidoreductase ThiO 999 1000 ctx neighborhood:881 fusion:838 cooccurence:709 coexpression:461 database:900 textmining:949
Rv0416 thiS sulfur carrier protein ThiS 999 999 ctx neighborhood:882 coexpression:873 experimental:926 textmining:828
Rv0414c thiE thiamine-phosphate synthase 994 990 ctx neighborhood:774 cooccurence:735 coexpression:852 textmining:434
Rv1335 cysO sulfur carrier protein CysO 976 974 experimental:973
Rv0423c thiC phosphomethylpyrimidine synthase 941 923 ctx cooccurence:500 coexpression:816
Rv3379c dxs2 1-deoxy-D-xylulose-5-phosphate synthase 938 901 database:900 textmining:410
Rv2682c dxs1 1-deoxy-D-xylulose 5-phosphate synthase 963 900 database:900 textmining:650
Rv1173 fbiC FO synthase 915 889 coexpression:804 experimental:413
Rv0422c thiD hydroxymethylpyrimidine/phosphomethylpyrimidine kinase 957 853 ctx cooccurence:422 coexpression:715 textmining:725
Rv3206c moeB1 adenylyltransferase/sulfurtransferase MoeZ 880 836 coexpression:729
Rv3116 moeB2 molybdenum cofactor biosynthesis protein MoeB 879 835 coexpression:729
Rv2338c moeW molybdopterin biosynthesis protein MoeW 776 759 coexpression:647
Rv1355c moeY molybdopterin biosynthesis protein MoeY 741 720 coexpression:647
Rv2337c hyp hypothetical protein 685 659 coexpression:648
Rv3196 hyp hypothetical protein 675 655 coexpression:643

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: thiazole synthase
  • MTBC0 PGAP product: thiazole synthase
  • Pfam (hmmscan --cut_ga): ThiG PF05690.21 (E=9e-108)
  • (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_214931.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ThiG (PF05690.21)
  • 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 COG2022
  • Curated reference: UniProt P9WG73 (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 — 28 functional partner(s); context anchor thiO
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000437|Rv0417|thiG
MAESKLVIGDRSFASRLIMGTGGATNLAVLEQALIASGTELTTVAIRRVDADGGTGLLDLLNRLGITPLPNTAGCRSAAEAVLTAQLAREALNTNWVKLEVIADERTLWPDAVELVRAAEQLVDDGFVVLPYTTDDPVLARRLEDTGCAAVMPLGSPIGTGLGIANPHNIEMIVAGARVPVVLDAGIGTASDAALAMELGCDAVLLASAVTRAADPPAMAAAMAAAVTAGYLARCAGRIPKRFWAQASSPAR