esxB Family assigned · medium auto-curated

H37Rv Rv3874 · MTBC0 mtbc0_004107 · 100 aa · 4376484–4376786 (+) · RefSeq NP_218391.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6-like protein EsxB
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 WXG100 family target CFP-10
Revised (this work)Type VII secretion system ESX-1 WXG100 family target CFP-10. Pfam: T7SS_ESX_EspC (PF10824.15), 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 P9WNK5 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxB
Curated functionA secreted protein. Acts as a strong host (human) T-cell antigen. Involved in translocation of bacteria from the host (human) phagolysosome to the host cytoplasm. Might serve as a chaperone to prevent uncontrolled membrane lysis by its partner EsxA; native protein binds poorly to artificial liposomes in the absence or presence of EsxA. EsxA and EsxA-EsxB are cytotoxic to pneumocytes. EsxB (and EsxA-EsxB but not EsxA alone) activates human neutrophils; EsxB transiently induces host (human) intracellular Ca(2+) mobility in a dose-dependent manner, monocytes and lymphocytes do not respond. Neutro.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameesxB
eggNOG descriptionBelongs to the WXG100 family
Orthologous groupCOG4842
Gene Ontology (36) GO:0002790, GO:0003674, GO:0005488, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0006810, GO:0008104, GO:0008150, GO:0009306 +24 more

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, 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
T7SS_ESX_EspCPF10824.15 3.4e-053–95 Excreted virulence factor EspC, type VII ESX diderm
WXG100PF06013.19 2.9e-184–88 Proteins of 100 residues with WXG

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3875 esxA ESAT-6 protein EsxA 999 1000 ctx neighborhood:833 coexpression:853 experimental:999 textmining:997
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 998 992 experimental:987 textmining:879
Rv3870 eccCa1 ESX-1 secretion system protein EccCa 937 821 ctx neighborhood:580 experimental:585 textmining:664
Rv1038c esxJ ESAT-6 like protein EsxJ 910 813 coexpression:813 textmining:540
Rv1198 esxL ESAT-6 like protein EsxL 901 803 coexpression:803 textmining:521
Rv3620c esxW ESAT-6 like protein EsxW 926 802 coexpression:802 textmining:644
Rv1197 esxK ESAT-6 like protein EsxK 898 802 coexpression:802 textmining:508
Rv2347c esxP ESAT-6 like protein EsxP 927 799 coexpression:799 textmining:653
Rv2346c esxO ESAT-6 like protein EsxO 899 796 coexpression:796 textmining:530
Rv3873 PPE68 PPE family protein PPE68 963 788 ctx neighborhood:776 textmining:834
Rv1793 esxN ESAT-6 like protein EsxN 916 761 coexpression:761 textmining:664
Rv3648c cspA cold shock protein A 782 736 coexpression:733
Rv0288 esxH ESAT-6-like protein EsxH 976 734 coexpression:734 textmining:915
Rv3619c esxV ESAT-6 like protein EsxV 898 731 coexpression:731 textmining:637
Rv3869 eccB1 ESX-1 secretion system protein EccB 843 727 ctx neighborhood:550 textmining:450

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 EsxB
  • MTBC0 PGAP product: type VII secretion system ESX-1 WXG100 family target CFP-10
  • Pfam (hmmscan --cut_ga): T7SS_ESX_EspC PF10824.15 (E=3e-05), WXG100 PF06013.19 (E=3e-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_218391.1)
  • Domains: Pfam-A via hmmscan --cut_ga — T7SS_ESX_EspC (PF10824.15), 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 P9WNK5 (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 — 87 functional partner(s); context anchor esxA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004107|Rv3874|esxB
MAEMKTDAATLAQEAGNFERISGDLKTQIDQVESTAGSLQGQWRGAAGTAAQAAVVRFQEAANKQKQELDEISTNIRQAGVQYSRADEEQQQALSSQMGF