pheA Resolved · high auto-curated

H37Rv Rv3838c · MTBC0 mtbc0_004068 · 321 aa · 4335815–4336780 (-) · RefSeq NP_218355.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)prephenate dehydratase
MTBC0 PGAP re-annotationprephenate dehydratase
Revised (this work)Prephenate dehydratase. Pfam: PDT (PF00800.24), ACT (PF01842.32).

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

Curated reference (UniProt)

UniProt P9WIC3 SwissProt · reviewed · Evidence at protein level
UniProt namePrephenate dehydratase
EC (curated) EC 4.2.1.51

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namepheA
eggNOG descriptionPrephenate dehydratase
Orthologous groupCOG0077
EC number EC 4.2.1.51
KEGG orthology K04518
KEGG pathways map00400, map01100, map01110, map01130, map01230
KEGG modules M00024
Gene Ontology (61) GO:0003674, GO:0003824, GO:0004664, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006082, GO:0006520, GO:0006558 +49 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 0.332 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 6 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
PDTPF00800.24 3.9e-444–190 Prephenate dehydratase
ACTPF01842.32 1.6e-11207–267 ACT domain

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

Closest characterised functional partner: Rv3837c (phosphoglycerate mutase), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3754 tyrA prephenate dehydrogenase TyrA 992 946 database:900 textmining:874
Rv0948c chorismate mutase 940 909 database:900
Rv1885c chorismate mutase 937 909 database:900
Rv2231c cobC aminotransferase 916 908 database:900
Rv3772 hisC2 histidinol-phosphate aminotransferase 916 907 database:900
Rv1600 hisC1 histidinol-phosphate aminotransferase 916 907 database:900
Rv3837c phosphoglycerate mutase 884 884 ctx neighborhood:882
Rv1908c katG catalase-peroxidase 801 801 database:800
Rv3839 hyp hypothetical protein 784 784 ctx neighborhood:781
Rv3565 aspB aspartate aminotransferase AspB 779 768 ctx fusion:528 database:500
Rv3002c ilvN acetolactate synthase small subunit 731 709 ctx cooccurence:502
Rv2386c mbtI salicylate synthase 746 641 database:500
Rv0337c aspC aspartate aminotransferase 646 627 database:500
Rv3840 transcriptional regulator 609 594 ctx neighborhood:591
Rv0884c serC phosphoserine aminotransferase 660 557 coexpression:520

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: prephenate dehydratase
  • MTBC0 PGAP product: prephenate dehydratase
  • Pfam (hmmscan --cut_ga): PDT PF00800.24 (E=4e-44), ACT PF01842.32 (E=2e-11)
  • (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_218355.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PDT (PF00800.24), ACT (PF01842.32)
  • 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 COG0077
  • Curated reference: UniProt P9WIC3 (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 — 49 functional partner(s); context anchor Rv3837c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004068|Rv3838c|pheA
MVRIAYLGPEGTFTEAALVRMVAAGLVPETGPDALQRMPVESAPAALAAVRDGGADYACVPIENSIDGSVLPTLDSLAIGVRLQVFAETTLDVTFSIVVKPGRNAADVRTLAAFPVAAAQVRQWLAAHLPAADLRPAYSNADAARQVADGLVDAAVTSPLAAARWGLAALADGVVDESNARTRFVLVGRPGPPPARTGADRTSAVLRIDNQPGALVAALAEFGIRGIDLTRIESRPTRTELGTYLFFVDCVGHIDDEAVAEALKAVHRRCADVRYLGSWPTGPAAGAQPPLVDEASRWLARLRAGKPEQTLVRPDDQGAQA