esxS Resolved · high auto-curated

H37Rv Rv3020c · MTBC0 - · 97 aa · 3379036–3379329 (-) · RefSeq YP_177919.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 like protein EsxS
MTBC0 PGAP re-annotation
Revised (this work)ESAT-6 like protein EsxS. 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 Q6MX18 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxS

Functional vocabulary (eggNOG-mapper, orthology transfer)

Preferred nameesxG
Orthologous group2A0FY
Gene Ontology (2) GO:0005575, GO:0032991

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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 3.1e-079–87 Proteins of 100 residues with WXG

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

Closest characterised functional partner: esxR (ESAT-6 like protein EsxR), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3019c esxR ESAT-6 like protein EsxR 999 1000 ctx neighborhood:682 coexpression:733 experimental:999 textmining:861
Rv3017c esxQ ESAT-6 like protein EsxQ 980 866 experimental:822 textmining:859
Rv0288 esxH ESAT-6-like protein EsxH 939 834 experimental:822 textmining:650
Rv3018c PPE46 PPE family protein PPE46 611 531
Rv3619c esxV ESAT-6 like protein EsxV 422 399
Rv3874 esxB ESAT-6-like protein EsxB 810 396 textmining:699
Rv1037c esxI ESAT-6 like protein EsxI 495 396
Rv2346c esxO ESAT-6 like protein EsxO 419 396
Rv3875 esxA ESAT-6 protein EsxA 836 394 textmining:741
Rv1038c esxJ ESAT-6 like protein EsxJ 625 394 textmining:407
Rv1198 esxL ESAT-6 like protein EsxL 546 394
Rv1793 esxN ESAT-6 like protein EsxN 532 394
Rv1197 esxK ESAT-6 like protein EsxK 526 393
Rv3620c esxW ESAT-6 like protein EsxW 470 393
Rv2347c esxP ESAT-6 like protein EsxP 470 393

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 EsxS
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=3e-07)
  • (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 YP_177919.1)
  • 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 2A0FY
  • Curated reference: UniProt Q6MX18 (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 — 29 functional partner(s); context anchor esxR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3020c|esxS
MSLLDAHIPQLIASHTAFAAKAGLMRHTIGQAEQQAMSAQAFHQGESAAAFQGAHARFVAAAAKVNTLLDIAQANLGEAAGTYVAADAAAASSYTGF