esxR Family assigned · medium auto-curated

H37Rv Rv3019c · MTBC0 mtbc0_003210 · 96 aa · 3400020–3400310 (-) · RefSeq NP_217535.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 like protein EsxR
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 P9WNI9 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxR

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameesxH
eggNOG descriptionBelongs to the WXG100 family
Orthologous groupCOG4842
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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.84% of strains (1219) · 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 9.6e-193–87 Proteins of 100 residues with WXG

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3020c esxS ESAT-6 like protein EsxS 999 1000 ctx neighborhood:682 coexpression:733 experimental:999 textmining:861
Rv0287 esxG ESAT-6 like protein EsxG 956 833 experimental:822 textmining:751
Rv3018c PPE46 PPE family protein PPE46 635 453
Rv3350c PPE56 PPE family protein PPE56 431 431 coexpression:431
Rv3018A PE27A Rv3018A, len: 28 aa. PE27A, Member of Mycobacterium tuberculosis PE family (see Brennan and Delogu, 2002), most similar to Rv0285 (102 aa), 652 407 ctx neighborhood:407 textmining:437
Rv0284 eccC3 ESX-3 secretion system protein EccC3 456 406
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 483 349
Rv0289 espG3 ESX-3 secretion-associated protein EspG3 518 145 textmining:460
Rv3022A PE29 PE family protein PE29 433 93 textmining:401
Rv1917c PPE34 PPE family protein PPE34 440 50 textmining:435
Rv1304 atpB ATP synthase subunit A 474 47 textmining:471
Rv3875 esxA ESAT-6 protein EsxA 693 44 textmining:692
Rv3874 esxB ESAT-6-like protein EsxB 605 44 textmining:605
Rv0294 tam trans-aconitate methyltransferase 541 44 textmining:540
Rv1038c esxJ ESAT-6 like protein EsxJ 540 44 textmining:539

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 EsxR
  • MTBC0 PGAP product: WXG100 family type VII secretion target
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=1e-18)
  • (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_217535.1)
  • 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 P9WNI9 (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 — 19 functional partner(s); context anchor esxS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003210|Rv3019c|esxR
MSQIMYNYPAMMAHAGDMAGYAGTLQSLGADIASEQAVLSSAWQGDTGITYQGWQTQWNQALEDLVRAYQSMSGTHESNTMAMLARDGAEAAKWGG