tpi Resolved · high auto-curated

H37Rv Rv1438 · MTBC0 mtbc0_001538 · 261 aa · 1624929–1625714 (+) · RefSeq NP_215954.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)triosephosphate isomerase
MTBC0 PGAP re-annotationtriose-phosphate isomerase
Revised (this work)Triose-phosphate isomerase. Pfam: TIM (PF00121.25).

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

Curated reference (UniProt)

UniProt P9WG43 SwissProt · reviewed · Evidence at protein level
UniProt nameTriosephosphate isomerase
EC (curated) EC 5.3.1.1
Curated functionInvolved in the gluconeogenesis. Catalyzes stereospecifically the conversion of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde-3-phosphate (G3P).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred nametpiA
eggNOG descriptionInvolved in the gluconeogenesis. Catalyzes stereospecifically the conversion of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde-3-phosphate (G3P)
Orthologous groupCOG0149
EC number EC 5.3.1.1
KEGG orthology K01803
KEGG pathways map00010, map00051, map00562, map00710, map01100, map01110, map01120, map01130, map01200, map01230
KEGG modules M00001, M00002, M00003
Gene Ontology (152) GO:0003674, GO:0003824, GO:0004807, GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0005975, GO:0005996 +140 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 0.226 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
TIMPF00121.25 1.1e-895–253 Triosephosphate isomerase

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

Closest characterised functional partner: pgk (phosphoglycerate kinase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1437 pgk phosphoglycerate kinase 999 1000 ctx neighborhood:882 fusion:900 cooccurence:656 coexpression:963 textmining:832
Rv1436 gap glyceraldehyde 3-phosphate dehydrogenase 999 1000 ctx neighborhood:882 fusion:471 cooccurence:680 coexpression:879 experimental:526 database:900 textmining:715
Rv0946c pgi glucose-6-phosphate isomerase 995 979 coexpression:851 database:800 textmining:804
Rv0363c fba fructose-bisphosphate aldolase 995 977 coexpression:763 database:900 textmining:831
Rv1023 eno enolase 985 941 coexpression:858 experimental:476 textmining:762
Rv0727c fucA L-fuculose phosphate aldolase FucA 941 923 database:900
Rv1448c tal transaldolase 969 908 coexpression:440 database:800 textmining:680
Rv1449c tkt transketolase 977 907 coexpression:447 database:800 textmining:769
Rv1617 pykA pyruvate kinase 958 905 ctx cooccurence:561 coexpression:781 textmining:576
Rv0478 deoC 2-deoxyribose-5-phosphate aldolase 881 845 database:800
Rv0489 gpm1 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 948 824 coexpression:787 textmining:720
Rv1121 zwf1 glucose-6-phosphate 1-dehydrogenase 871 818 database:800
Rv1447c zwf2 glucose-6-phosphate 1-dehydrogenase 891 814 database:800 textmining:440
Rv3010c pfkA 6-phosphofructokinase 945 811 coexpression:707 textmining:725
Rv2881c cdsA phosphatidate cytidylyltransferase 811 774 coexpression:703

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: triosephosphate isomerase
  • MTBC0 PGAP product: triose-phosphate isomerase
  • Pfam (hmmscan --cut_ga): TIM PF00121.25 (E=1e-89)
  • (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_215954.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TIM (PF00121.25)
  • 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 COG0149
  • Curated reference: UniProt P9WG43 (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 — 173 functional partner(s); context anchor pgk
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001538|Rv1438|tpi
MSRKPLIAGNWKMNLNHYEAIALVQKIAFSLPDKYYDRVDVAVIPPFTDLRSVQTLVDGDKLRLTYGAQDLSPHDSGAYTGDVSGAFLAKLGCSYVVVGHSERRTYHNEDDALVAAKAATALKHGLTPIVCIGEHLDVREAGNHVAHNIEQLRGSLAGLLAEQIGSVVIAYEPVWAIGTGRVASAADAQEVCAAIRKELASLASPRIADTVRVLYGGSVNAKNVGDIVAQDDVDGGLVGGASLDGEHFATLAAIAAGGPLP