PE_PGRS17 Family assigned · medium auto-curated

H37Rv Rv0978c · MTBC0 - · 331 aa · 1093361–1094356 (-) · RefSeq YP_177774.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE-PGRS family protein PE_PGRS17
MTBC0 PGAP re-annotation
Revised (this work)PE-PGRS family protein PE_PGRS17. Pfam: PE (PF00934.26), PGRS (PF21526.3), NHL (PF01436.28).

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 Q79FU2 SwissProt · reviewed · Evidence at protein level
UniProt namePE-PGRS family protein PE_PGRS17
Curated functionInduces maturation and activation of human dendritic cells (DCs), via TLR2-dependent activation of ERK1/2, p38 MAPK, and NF-kappa-B signaling pathways, and enhances the ability of DCs to stimulate CD4(+) T cells. By activating DCs, could potentially contribute to the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
O Post-translational modification, protein turnover, chaperones
eggNOG descriptionamine dehydrogenase activity
Orthologous groupCOG3391

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 0.151 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 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
PEPF00934.26 1.6e-284–92 PE family
PGRSPF21526.3 2.3e-10117–184 PGRS repeats
NHLPF01436.28 8.6e-07217–243 NHL repeat

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

Closest characterised functional partner: Rv2209 (integral membrane protein), medium confidence from genomic context alone (score 436 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1057 hyp hypothetical protein 750 750 ctx cooccurence:750
Rv2383c mbtB phenyloxazoline synthase 668 668 coexpression:657
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 670 650 experimental:622
Rv1157c hyp hypothetical protein 536 537 coexpression:417
Rv0330c hyp hypothetical protein 458 458 ctx cooccurence:458
Rv2209 integral membrane protein 436 436 ctx cooccurence:436
Rv3800c pks13 polyketide synthase 426 426 coexpression:400
Rv2384 mbtA 2,3-dihydroxybenzoate-AMP ligase 420 420 coexpression:409
Rv2737A Rv2737A, len: 57 aa. Conserved hypothetical cys-rich protein (possibly gene fragment), similar to central part of AJ243803_1|glgA from Strep 414 414 coexpression:414
Rv3350c PPE56 PPE family protein PPE56 413 413 ctx cooccurence:413
Rv3347c PPE55 PPE family protein PPE55 410 410 ctx cooccurence:410
Rv0341 iniB isoniazid inducible protein IniB 408 409 ctx cooccurence:400
Rv0979c hyp hypothetical protein 828 405 ctx neighborhood:405 textmining:723
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 406 405 coexpression:400
Rv1045 hyp hypothetical protein 405 405 ctx cooccurence:405

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): PE-PGRS family protein PE_PGRS17
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=2e-28), PGRS PF21526.3 (E=2e-10), NHL PF01436.28 (E=9e-07)
  • (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 YP_177774.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3), NHL (PF01436.28)
  • 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 COG3391
  • Curated reference: UniProt Q79FU2 (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 — 27 functional partner(s); context anchor Rv2209
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0978c|PE_PGRS17
MSFVNVAPQLVSTAAADAARIGSAINTANTAAAATTQVLAAAQDEVSTAIAALFGSHGQHYQAISAQVAAYQQRFVLALSQAGSTYAVAEAASATPLQNVLDAINAPVQSLTGRPLIGDGANGIDGTGQAGGNGGWLWGNGGNGGSGAPGQAGGAGGAAGLIGNGGAGGTGGAVSLARAGTAGGAGRGPVGGIGGAGGVGGAGGAAGAVTTITHASFNDPHGVAVNPGGNVYVTNFGSGTVSVINPATNTVTGSPITIGNGPSGVAVSPVTGLVFVTNFDSNTVSVIDPTTNTVTGSPITVGTAPTGVAVNPVTGEVYVTNFAGDTVSVIS