espG3 Resolved · high auto-curated

H37Rv Rv0289 · MTBC0 mtbc0_000308 · 295 aa · 355443–356330 (+) · RefSeq NP_214803.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-3 secretion-associated protein EspG3
MTBC0 PGAP re-annotationtype VII secretion system ESX-3 associated protein EspG3
Revised (this work)Type VII secretion system ESX-3 associated protein EspG3. Pfam: ESX-1_EspG (PF14011.12).

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

Curated reference (UniProt)

UniProt P9WJC7 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-3 secretion-associated protein EspG3
Curated functionSpecific chaperone for cognate PE/PPE proteins. Plays an important role in preventing aggregation of PE/PPE dimers.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameespG3
eggNOG descriptionEspG family
Orthologous group2A0WB
Gene Ontology (2) GO:0008150, GO:0040007

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 0.457 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (664) · 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
ESX-1_EspGPF14011.12 1.8e-5911–269 EspG family

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

Closest characterised functional partner: mycP3 (membrane-anchored mycosin MycP), high confidence from genomic context alone (score 970 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0291 mycP3 membrane-anchored mycosin MycP 989 970 ctx neighborhood:815 coexpression:845 textmining:667
Rv0290 eccD3 ESX-3 secretion system protein EccD 996 969 ctx neighborhood:815 coexpression:841 textmining:878
Rv0292 eccE3 ESX-3 secretion system protein EccE 988 966 ctx neighborhood:815 coexpression:822 textmining:678
Rv0288 esxH ESAT-6-like protein EsxH 980 963 ctx neighborhood:859 coexpression:751 textmining:484
Rv0287 esxG ESAT-6 like protein EsxG 974 940 ctx neighborhood:707 coexpression:802 textmining:595
Rv0286 PPE4 PPE family protein PPE4 954 936 ctx neighborhood:564 coexpression:860
Rv0283 eccB3 ESX-3 secretion system protein EccB3 974 926 ctx neighborhood:734 coexpression:733 textmining:672
Rv0282 eccA3 ESX-3 secretion system protein EccA 915 845 ctx neighborhood:767 textmining:473
Rv0284 eccC3 ESX-3 secretion system protein EccC3 916 842 ctx neighborhood:768 textmining:493
Rv0285 PE5 PE family protein PE5 715 597 ctx neighborhood:597
Rv0281 S-adenosylmethionine-dependent methyltransferase 426 426
Rv0280 PPE3 PPE family protein PPE3 464 333
Rv3020c esxS ESAT-6 like protein EsxS 469 168
Rv3019c esxR ESAT-6 like protein EsxR 518 145 textmining:460
Rv3874 esxB ESAT-6-like protein EsxB 422 83

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-3 secretion-associated protein EspG3
  • MTBC0 PGAP product: type VII secretion system ESX-3 associated protein EspG3
  • Pfam (hmmscan --cut_ga): ESX-1_EspG PF14011.12 (E=2e-59)
  • (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_214803.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ESX-1_EspG (PF14011.12)
  • 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 2A0WB
  • Curated reference: UniProt P9WJC7 (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 mycP3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000308|Rv0289|espG3
MDATPNAVELTVDNAWFIAETIGAGTFPWVLAITMPYSDAAQRGAFVDRQRDELTRMGLLSPQGVINPAVADWIKVVCFPDRWLDLRYVGPASADGACELLRGIVALRTGTGKTSNKTGNGVVALRNAQLVTFTAMDIDDPRALVPILGVGLAHRPPARFDEFSLPTRVGARADERLRSGVPLGEVVDYLGIPASARPVVESVFSGPRSYVEIVAGCNRDGRHTTTEVGLSIVDTSAGRVLVSPSRAFDGEWVSTFSPGTPFAIAVAIQTLTACLPDGQWFPGQRVSRDFSTQSS