espB Resolved · high auto-curated

H37Rv Rv3881c · MTBC0 mtbc0_004115 · 460 aa · 4384789–4386171 (-) · RefSeq NP_218398.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-1 secretion-associated protein EspB
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 target EspB
Revised (this work)Type VII secretion system ESX-1 target EspB. Pfam: EspB_PE (PF18625.8), EspB_PPE (PF21856.3).

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

Curated reference (UniProt)

UniProt P9WJD9 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-1 secretion-associated protein EspB
Curated functionRequired for host-cell death and may support an EsxA-independent virulence function. Secreted processed form of EspB binds to phosphatidic acid and phosphatidylserine. Inhibits IFN-gamma-induced autophagy in murine macrophages.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Preferred nameespB
Orthologous group2F9DC
Gene Ontology (29) GO:0002790, GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0006810, GO:0008104, GO:0008150, GO:0009306, GO:0009405, GO:0009987 +17 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) pseudogene candidate

pN/pS 1.571 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 14 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 4.93% of strains (7158) · 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
EspB_PEPF18625.8 8.2e-3212–88 ESX-1 secreted protein B PE domain
EspB_PPEPF21856.3 7.8e-66130–281 ESX-1 secretion-associated protein EspB, PPE domain

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

Closest characterised functional partner: espL (ESX-1 secretion-associated protein EspL), high confidence from genomic context alone (score 978 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3880c espL ESX-1 secretion-associated protein EspL 995 978 ctx neighborhood:882 coexpression:822 textmining:817
Rv3879c espK ESX-1 secretion-associated protein EspK 989 912 experimental:900 textmining:886
Rv3882c eccE1 ESX-1 secretion system protein EccE1 923 772 ctx neighborhood:769 textmining:676
Rv3883c mycP1 membrane-anchored mycosin 950 745 ctx neighborhood:731 textmining:812
Rv3864 espE ESX-1 secretion-associated protein EspE 954 737 coexpression:734 textmining:834
Rv3873 PPE68 PPE family protein PPE68 648 531 coexpression:474
Rv1075c hyp hypothetical protein 496 472 experimental:425
Rv2418c octT hyp hypothetical protein 495 471 experimental:425
Rv0518 hyp hypothetical protein 494 470 experimental:425
Rv3866 espG1 ESX-1 secretion-associated protein EspG 711 441 coexpression:441 textmining:505
Rv1975 hyp hypothetical protein 440 440 coexpression:430
Rv0157A hyp hypothetical protein 438 439 coexpression:429
Rv0058 dnaB replicative DNA helicase 449 427 coexpression:407
Rv3867 espH ESX-1 secretion-associated protein EspH 713 363 textmining:568
Rv3878 espJ ESX-1 secretion-associated protein EspJ 791 311 textmining:710

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: ESX-1 secretion-associated protein EspB
  • MTBC0 PGAP product: type VII secretion system ESX-1 target EspB
  • Pfam (hmmscan --cut_ga): EspB_PE PF18625.8 (E=8e-32), EspB_PPE PF21856.3 (E=8e-66)
  • (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_218398.1)
  • Domains: Pfam-A via hmmscan --cut_ga — EspB_PE (PF18625.8), EspB_PPE (PF21856.3)
  • 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 2F9DC
  • Curated reference: UniProt P9WJD9 (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 — 38 functional partner(s); context anchor espL
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004115|Rv3881c|espB
MTQSQTVTVDQQEILNRANEVEAPMADPPTDVPITPCELTAAKNAAQQLVLSADNMREYLAAGAKERQRLATSLRNAAKAYGEVDEEAATALDNDGEGTVQAESAGAVGGDSSAELTDTPRVATAGEPNFMDLKEAARKLETGDQGASLAHFADGWNTFNLTLQGDVKRFRGFDNWEGDAATACEASLDQQRQWILHMAKLSAAMAKQAQYVAQLHVWARREHPTYEDIVGLERLYAENPSARDQILPVYAEYQQRSEKVLTEYNNKAALEPVNPPKPPPAIKIDPPPPPQEQGLIPGFLMPPSDGSGVTPGTGMPAAPMVPPTGSPGGGLPADTAAQLTSAGREAAALSGDVAVKAASLGGGGGGGVPSAPLGSAIGGAESVRPAGAGDIAGLGQGRAGGGAALGGGGMGMPMGAAHQGQGGAKSKGSQQEDEALYTEDRAWTEAVIGNRRRQDSKESK