egtE Resolved · high auto-curated

H37Rv Rv3700c · MTBC0 mtbc0_003922 · 390 aa · 4166696–4167868 (-) · RefSeq NP_218217.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)pyridoxal-phosphate-dependent protein EgtE
MTBC0 PGAP re-annotationergothioneine biosynthesis PLP-dependent enzyme EgtE
Revised (this work)Ergothioneine biosynthesis PLP-dependent enzyme EgtE. Pfam: Aminotran_5 (PF00266.26).

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

Curated reference (UniProt)

UniProt O69668 SwissProt · reviewed · Evidence at protein level
UniProt nameHercynylcysteine sulfoxide lyase
EC (curated) EC 4.4.1.36
Curated functionCatalyzes a C-S bond cleavage, converting hercynylcysteine sulfoxide to 2-sulfenohercynine, a sulfenic acid intermediate that can be spontaneously reduced to ergothioneine. Ergothioneine is a secreted antioxidant that protects mycobacterium from oxidative stress.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameegtE
eggNOG descriptionBelongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. EgtE subfamily
Orthologous groupCOG0520
EC number EC 4.4.1.36
KEGG orthology K18913
KEGG pathways map00340
Gene Ontology (59) GO:0000096, GO:0000097, GO:0006082, GO:0006520, GO:0006547, GO:0006548, GO:0006575, GO:0006577, GO:0006578, GO:0006725, GO:0006790, GO:0006807 +47 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 0.189 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 5 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
Aminotran_5PF00266.26 2.2e-3030–375 Aminotransferase class-V

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

Closest characterised functional partner: egtC (amidohydrolase EgtC), high confidence from genomic context alone (score 992 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3702c egtC amidohydrolase EgtC 996 992 ctx neighborhood:839 coexpression:441 database:900 textmining:598
Rv3701c egtD histidine-specific methyltransferase EtgD 982 955 ctx neighborhood:839 coexpression:734 textmining:623
Rv1465 nitrogen fixation related protein 968 952 coexpression:692 experimental:785
Rv3704c gshA glutamate--cysteine ligase 954 885 ctx neighborhood:839 textmining:623
Rv3703c etgB iron(II)-dependent oxidoreductase EgtB 968 882 ctx neighborhood:839 textmining:745
Rv0888 spmT hyp hypothetical protein 783 784 experimental:780
Rv1463 sufC ABC transporter ATP-binding protein 957 773 coexpression:693 textmining:822
Rv1462 sufD hyp hypothetical protein 953 758 coexpression:648 textmining:815
Rv1461 sufB hyp hypothetical protein 761 746 coexpression:648
Rv3284 hyp hypothetical protein 700 669 experimental:490
Rv0048c membrane protein 578 578 ctx cooccurence:577
Rv0517 acyltransferase 572 572 ctx cooccurence:567
Rv3779 transmembrane protein 562 562 ctx cooccurence:548
Rv3705c hyp hypothetical protein 560 560 ctx neighborhood:553
Rv2345 transmembrane protein 464 465

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: pyridoxal-phosphate-dependent protein EgtE
  • MTBC0 PGAP product: ergothioneine biosynthesis PLP-dependent enzyme EgtE
  • Pfam (hmmscan --cut_ga): Aminotran_5 PF00266.26 (E=2e-30)
  • (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_218217.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Aminotran_5 (PF00266.26)
  • 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 COG0520
  • Curated reference: UniProt O69668 (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 — 23 functional partner(s); context anchor egtC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003922|Rv3700c|egtE
MRRSGANSPAGDSLADRWRAARPPVAGLHLDSAACSRQSFAALDAAAQHARHEAEVGGYVAAEAAAAVLDAGRAAVAALSGLPDAEVVFTTGSLHALDLLLGSWPGENRTLACLPGEYGPNLAVMAAHGFDVRPLPTLQDGRVALDDAAFMLADDPPDLVHLTVVASHRGVAQPLAMVAQLCTELKLPLVVDAAQGLGHVDCAVGADVTYASSRKWIAGPRGVGVLAVRPELMERLRARLPAPDWMPPLTVAQQLGFGEANVAARVGFSVALGEHLACGPQAIRARLAELGDIARTVLADVSGWRVVEAVDEPSAITTLAPIDGADPAAVRAWLLSQRRIVTTYAGVERAPLELPAPVLRISPHVDNTADDLDAFAEALVAATAATSGER