espE Resolved · high auto-curated

H37Rv Rv3864 · MTBC0 mtbc0_004097 · 418 aa · 4364379–4365635 (+) · RefSeq NP_218381.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-1 secretion-associated protein EspE
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 associated protein EspE
Revised (this work)Type VII secretion system ESX-1 associated protein EspE. Pfam: EspA_EspE (PF18879.7).

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

Curated reference (UniProt)

UniProt P9WJD3 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-1 secretion-associated protein EspE

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptiondomain, Protein
Orthologous groupCOG3266
Gene Ontology (8) GO:0008150, GO:0040007, GO:0044110, GO:0044116, GO:0044117, GO:0044403, GO:0044419, GO:0051704

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 0.516 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 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
EspA_EspEPF18879.7 2.1e-2322–104 EspA/EspE family

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

Closest characterised functional partner: espG1 (ESX-1 secretion-associated protein EspG), high confidence from genomic context alone (score 935 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3866 espG1 ESX-1 secretion-associated protein EspG 946 935 ctx neighborhood:594 coexpression:846
Rv3876 espI ESX-1 secretion-associated protein EspI 941 884 ctx cooccurence:436 coexpression:774 textmining:518
Rv3873 PPE68 PPE family protein PPE68 894 883 coexpression:850
Rv1917c PPE34 PPE family protein PPE34 776 777 ctx cooccurence:771
Rv3350c PPE56 PPE family protein PPE56 780 776 ctx cooccurence:773
Rv3347c PPE55 PPE family protein PPE55 775 775 ctx cooccurence:772
Rv0355c PPE8 PPE family protein PPE8 774 775 ctx cooccurence:772
Rv0304c PPE5 PPE family protein PPE5 774 774 ctx cooccurence:771
Rv3343c PPE54 PPE family protein PPE54 773 773 ctx cooccurence:771
Rv3879c espK ESX-1 secretion-associated protein EspK 830 772 ctx cooccurence:772
Rv1004c membrane protein 771 772 ctx cooccurence:770
Rv0341 iniB isoniazid inducible protein IniB 776 771 ctx cooccurence:770
Rv0755c PPE12 PPE family protein PPE12 771 771 ctx cooccurence:768
Rv2082 hyp hypothetical protein 778 770 ctx cooccurence:760
Rv1753c PPE24 PPE family protein PPE24 770 770 ctx cooccurence:768

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: ESX-1 secretion-associated protein EspE
  • MTBC0 PGAP product: type VII secretion system ESX-1 associated protein EspE
  • Pfam (hmmscan --cut_ga): EspA_EspE PF18879.7 (E=2e-23)
  • (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_218381.1)
  • Domains: Pfam-A via hmmscan --cut_ga — EspA_EspE (PF18879.7)
  • 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 COG3266
  • Curated reference: UniProt P9WJD3 (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 — 138 functional partner(s); context anchor espG1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004097|Rv3864|espE
MASGSGLCKTTSNFIWGQLLLLGEGIPDPGDIFNTGSSLFKQISDKMGLAIPGTNWIGQAAEAYLNQNIAQQLRAQVMGDLDKLTGNMISNQAKYVSDTRDVLRAMKKMIDGVYKVCKGLEKIPLLGHLWSWELAIPMSGIAMAVVGGALLYLTIMTLMNATNLRGILGRLIEMLTTLPKFPGLPGLPSLPDIIDGLWPPKLPDIPIPGLPDIPGLPDFKWPPTPGSPLFPDLPSFPGFPGFPSLPGFPGLPGFPEFPAIPGFPALPGLPSIPNLFPGLPGLGDLLPGVGDLGKLPTWTELAALPDFLGGFAGLPSLGFGNLLSFASLPTVGQVTATMGQLQQLVAAGGGPSQLASMGSQQAQLISSQAQQGGQQHATLVSDKKEDEEGAAAGVAEAERAPIDAGTAASQRGQEGTVL