esxE Resolved · high auto-curated

H37Rv Rv3904c · MTBC0 - · 90 aa · 4390437–4390709 (-) · RefSeq NP_218421.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 like protein EsxE
MTBC0 PGAP re-annotation
Revised (this work)ESAT-6 like protein EsxE. Pfam: WXG100 (PF06013.19).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WNH9 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxE

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameesxE
eggNOG descriptionBelongs to the WXG100 family
Orthologous groupCOG4842

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 0.642 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
WXG100PF06013.19 1.3e-091–80 Proteins of 100 residues with WXG

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

Closest characterised functional partner: esxF (ESAT-6 like protein EsxF), high confidence from genomic context alone (score 922 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3903c cpnT hyp hypothetical protein 985 948 ctx neighborhood:882 coexpression:580 textmining:723
Rv3905c esxF ESAT-6 like protein EsxF 992 922 ctx neighborhood:880 textmining:907
Rv3902c ift hyp hypothetical protein 941 883 ctx neighborhood:882 textmining:522
Rv3906c hyp hypothetical protein 957 641 ctx neighborhood:629 textmining:885
Rv3907c pcnA poly(A) polymerase PcnA 585 585 ctx neighborhood:582
Rv0287 esxG ESAT-6 like protein EsxG 444 391
Rv3020c esxS ESAT-6 like protein EsxS 540 390
Rv3447c eccC4 ESX-4 secretion system protein EccC4 440 379
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 654 376 textmining:469
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 522 361
Rv0284 eccC3 ESX-3 secretion system protein EccC3 512 360
Rv2748c ftsK DNA translocase FtsK 454 351
Rv3911 sigM ECF RNA polymerase sigma factor SigM 428 266
Rv3445c esxU ESAT-6 like protein EsxU 536 135 textmining:486
Rv3448 eccD4 ESX-4 secretion system protein EccD4 526 116 textmining:486

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): ESAT-6 like protein EsxE
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=1e-09)
  • (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_218421.1)
  • Domains: Pfam-A via hmmscan --cut_ga — WXG100 (PF06013.19)
  • 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 COG4842
  • Curated reference: UniProt P9WNH9 (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 — 24 functional partner(s); context anchor esxF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3904c|esxE
MDPTVLADAVARMAEFGRHVEELVAEIESLVTRLHVTWTGEGAAAHAEAQRHWAAGEAMMRQALAQLTAAGQSAHANYTGAMATNLGMWS