espG2 Resolved · high auto-curated

H37Rv Rv3889c · MTBC0 mtbc0_004123 · 276 aa · 4397046–4397876 (-) · RefSeq NP_218406.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-2 secretion-associated protein EspG2
MTBC0 PGAP re-annotationtype VII secretion system ESX-2 associated protein EspG2
Revised (this work)Type VII secretion system ESX-2 associated protein EspG2. 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 P9WJC9 SwissProt · reviewed · Inferred from homology
UniProt nameESX-2 secretion-associated protein EspG2
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
eggNOG descriptionEspG family
Orthologous group2A2YZ

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 0.381 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 5.43% of strains (7886) · 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 1.5e-335–257 EspG family

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

Closest characterised functional partner: esxC (ESAT-6 like protein EsxC), medium confidence from genomic context alone (score 612 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3890c esxC ESAT-6 like protein EsxC 860 612 ctx neighborhood:549 textmining:655
Rv3888c membrane protein 946 606 ctx neighborhood:590 textmining:870
Rv3885c eccE2 ESX-2 secretion system protein EccE 597 597 ctx neighborhood:593
Rv3886c mycP2 membrane-anchored mycosin 576 577 ctx neighborhood:551
Rv3887c eccD2 ESX-2 secretion system protein EccD 942 574 ctx neighborhood:551 textmining:870
Rv3891c esxD ESAT-6 like protein EsxD 495 495 ctx neighborhood:479
Rv3884c eccA2 ESX-2 secretion system protein EccA 544 447 ctx neighborhood:444
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 452 78 textmining:431
Rv0994 moeA1 molybdopterin molybdenumtransferase 1 602 46 textmining:600
Rv0438c moeA2 molybdopterin molybdenumtransferase 601 44 textmining:600

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-2 secretion-associated protein EspG2
  • MTBC0 PGAP product: type VII secretion system ESX-2 associated protein EspG2
  • Pfam (hmmscan --cut_ga): ESX-1_EspG PF14011.12 (E=2e-33)
  • (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_218406.1)
  • 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 2A2YZ
  • Curated reference: UniProt P9WJC9 (SwissProt, reviewed; Inferred from homology)
  • 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 — 10 functional partner(s); context anchor esxC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004123|Rv3889c|espG2
MLTTTVDGLWVLQAVTGVEQTCPELGLRPLLPRLDTAERALRHPVAAELMAVGALDQAGNADPMVREWLTVLLRRDLGLLVTIGVPGGEPTRAAICRFATWWVVLERHGNLVRLYPAGTASDEAGAGELVVGQVERLCGVAEAAPLRPVTVDADELLHAVRDAGTLRSYLLSQRLDVDQLQMVTMAADPTRSAHATLVALQAGVGPEKSARILVGDSTVAIVDTAAGRICVESVTSGQRRYQVLSPGSRSDIGGAVQRLIRRLPAGDEWYSYRRVV