trpA Family assigned · medium auto-curated

H37Rv Rv1613 · MTBC0 mtbc0_001719 · 270 aa · 1824323–1825135 (+) · RefSeq NP_216129.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)tryptophan synthase subunit alpha
MTBC0 PGAP re-annotationtryptophan synthase subunit alpha
Revised (this work)Tryptophan synthase subunit alpha. Pfam: Trp_syntA (PF00290.27).

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

Curated reference (UniProt)

UniProt P9WFY1 SwissProt · reviewed · Evidence at protein level
UniProt nameTryptophan synthase alpha chain
EC (curated) EC 4.2.1.20
Curated functionThe alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nametrpA
eggNOG descriptionThe alpha subunit is responsible for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3- phosphate
Orthologous groupCOG0159
EC number EC 4.2.1.20
KEGG orthology K01695
KEGG pathways map00260, map00400, map01100, map01110, map01130, map01230
KEGG modules M00023
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944

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 0.228 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 3 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
Trp_syntAPF00290.27 7.6e-6816–249 Tryptophan synthase alpha chain

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

Closest characterised functional partner: trpC (indole-3-glycerol phosphate synthase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1611 trpC indole-3-glycerol phosphate synthase 999 1000 ctx neighborhood:793 cooccurence:774 coexpression:925 database:900 textmining:754
Rv1612 trpB tryptophan synthase subunit beta 999 1000 ctx neighborhood:882 fusion:900 cooccurence:774 coexpression:979 experimental:999 database:900 textmining:843
Rv1614 lgt prolipoprotein diacylglyceryl transferase 995 996 ctx neighborhood:882 coexpression:964
Rv1609 trpE anthranilate synthase component I 995 975 ctx neighborhood:721 cooccurence:767 coexpression:651 textmining:818
Rv2192c trpD anthranilate phosphoribosyltransferase 994 973 ctx cooccurence:774 coexpression:857 textmining:790
Rv0013 trpG anthranilate synthase component II 974 964 ctx cooccurence:760 coexpression:819
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 941 941 coexpression:941
Rv1559 ilvA threonine dehydratase IlvA 934 924 database:900
Rv2386c mbtI salicylate synthase 958 922 ctx cooccurence:761 coexpression:648 textmining:487
Rv1093 glyA1 serine hydroxymethyltransferase 922 912 database:900
Rv0070c glyA2 serine hydroxymethyltransferase 921 911 database:900
Rv3042c serB2 phosphoserine phosphatase SerB 910 908 database:900
Rv1077 cbs cystathionine beta-synthase 915 906 database:900
Rv0069c sdaA L-serine dehydratase 908 905 database:900
Rv0436c pssA CDP-diacylglycerol--serine O-phosphatidyltransferase 900 901 database:900

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: tryptophan synthase subunit alpha
  • MTBC0 PGAP product: tryptophan synthase subunit alpha
  • Pfam (hmmscan --cut_ga): Trp_syntA PF00290.27 (E=8e-68)
  • (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_216129.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Trp_syntA (PF00290.27)
  • 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 COG0159
  • Curated reference: UniProt P9WFY1 (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 — 108 functional partner(s); context anchor trpC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001719|Rv1613|trpA
MVAVEQSEASRLGPVFDSCRANNRAALIGYLPTGYPDVPASVAAMTALVESGCDIIEVGVPYSDPGMDGPTIARATEAALRGGVRVRDTLAAVEAISIAGGRAVVMTYWNPVLRYGVDAFARDLAAAGGLGLITPDLIPDEAQQWLAASEEHRLDRIFLVAPSSTPERLAATVEASRGFVYAASTMGVTGARDAVSQAAPELVGRVKAVSDIPVGVGLGVRSRAQAAQIAQYADGVIVGSALVTALTEGLPRLRALTGELAAGVRLGMSA