esxV Resolved · high auto-curated

H37Rv Rv3619c · MTBC0 - · 94 aa · 4059984–4060268 (-) · RefSeq NP_218136.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 like protein EsxV
MTBC0 PGAP re-annotation
Revised (this work)ESAT-6 like protein EsxV. 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 P0DOA7 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxV
Curated functionProbable virulence factor. In mice, elicits increased levels of IFN-gamma, IL-12 and IgG(2a), indicating a dominant Th1 host immune response.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBelongs to the WXG100 family
Orthologous group2BPBT

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 0.19 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 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 2.9e-153–87 Proteins of 100 residues with WXG

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

Closest characterised functional partner: esxW (ESAT-6 like protein EsxW), high confidence from genomic context alone (score 957 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3620c esxW ESAT-6 like protein EsxW 993 957 ctx neighborhood:703 coexpression:860 textmining:853
Rv2346c esxO ESAT-6 like protein EsxO 861 860 coexpression:860
Rv1198 esxL ESAT-6 like protein EsxL 860 860 coexpression:860
Rv1793 esxN ESAT-6 like protein EsxN 860 860 coexpression:860
Rv2347c esxP ESAT-6 like protein EsxP 955 853 coexpression:848 textmining:713
Rv1197 esxK ESAT-6 like protein EsxK 918 853 coexpression:848 textmining:470
Rv1038c esxJ ESAT-6 like protein EsxJ 892 853 coexpression:848
Rv1037c esxI ESAT-6 like protein EsxI 833 833 coexpression:833
Rv1196 PPE18 PPE family protein PPE18 858 803 coexpression:803
Rv3875 esxA ESAT-6 protein EsxA 908 748 coexpression:748 textmining:651
Rv3648c cspA cold shock protein A 741 741 coexpression:738
Rv3874 esxB ESAT-6-like protein EsxB 898 731 coexpression:731 textmining:637
Rv3621c PPE65 PPE family protein PPE65 550 550 ctx neighborhood:545
Rv3622c PE32 PE family protein PE32 624 545 ctx neighborhood:545
Rv0287 esxG ESAT-6 like protein EsxG 568 423

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 EsxV
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=3e-15)
  • (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_218136.1)
  • 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 2BPBT
  • Curated reference: UniProt P0DOA7 (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 — 22 functional partner(s); context anchor esxW
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3619c|esxV
MTINYQFGDVDAHGAMIRAQAGSLEAEHQAIISDVLTASDFWGGAGSAACQGFITQLGRNFQVIYEQANAHGQKVQAAGNNMAQTDSAVGSSWA