esxD Family assigned · medium auto-curated

H37Rv Rv3891c · MTBC0 mtbc0_004125 · 107 aa · 4398295–4398618 (-) · RefSeq NP_218408.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 like protein EsxD
MTBC0 PGAP re-annotationWXG100 family type VII secretion target
Revised (this work)WXG100 family type VII secretion target. Pfam: WXG100 (PF06013.19).

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

Curated reference (UniProt)

UniProt O05453 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxD

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameesxD
eggNOG descriptionProteins of 100 residues with WXG
Orthologous group2A33T

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) pseudogene candidate

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 9.86% of strains (14320) · clonal

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 3.4e-125–90 Proteins of 100 residues with WXG

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

Closest characterised functional partner: esxC (ESAT-6 like protein EsxC), high confidence from genomic context alone (score 757 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3890c esxC ESAT-6 like protein EsxC 937 757 ctx neighborhood:743 textmining:751
Rv3892c PPE69 PPE family protein PPE69 571 571 ctx neighborhood:568
Rv3893c PE36 PE family protein PE36 501 501 ctx neighborhood:501
Rv3889c espG2 ESX-2 secretion-associated protein EspG2 495 495 ctx neighborhood:479
Rv0287 esxG ESAT-6 like protein EsxG 441 51 textmining:436
Rv1793 esxN ESAT-6 like protein EsxN 403 50
Rv1168c PPE17 PPE family protein PPE17 488 46 textmining:486
Rv3445c esxU ESAT-6 like protein EsxU 453 41 textmining:454

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: ESAT-6 like protein EsxD
  • MTBC0 PGAP product: WXG100 family type VII secretion target
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=3e-12)
  • (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_218408.1)
  • 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 2A33T
  • Curated reference: UniProt O05453 (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 — 8 functional partner(s); context anchor esxC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004125|Rv3891c|esxD
MADTIQVTPQMLRSTANDIQANMEQAMGIAKGYLANQENVMNPATWSGAGVVASHMTATEITNELNKVLTGGTRLAEGLVQAAALMEGHEADSQTAFQALFGASHGS