PE5 Family assigned · medium auto-curated

H37Rv Rv0285 · MTBC0 - · 102 aa · 349624–349932 (+) · RefSeq YP_177710.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE family protein PE5
MTBC0 PGAP re-annotation
Revised (this work)PE family protein PE5. Pfam: PE (PF00934.26).

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 L7N695 SwissProt · reviewed · Evidence at protein level
UniProt namePE family immunomodulator PE5
Curated functionImportant for the siderophore-mediated iron-acquisition function of ESX-3. May play a pivotal role in the evasion of host immune response by M.tuberculosis. Mediates production of IL-10 via activation of the p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathways.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionCell motility protein
Orthologous group2B7DA

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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 1.5e-203–93 PE family

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

Closest characterised functional partner: eccB3 (ESX-3 secretion system protein EccB3), high confidence from genomic context alone (score 882 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0283 eccB3 ESX-3 secretion system protein EccB3 924 882 ctx neighborhood:882
Rv0282 eccA3 ESX-3 secretion system protein EccA 894 882 ctx neighborhood:882
Rv0284 eccC3 ESX-3 secretion system protein EccC3 881 881 ctx neighborhood:881
Rv0286 PPE4 PPE family protein PPE4 990 801 ctx neighborhood:801 textmining:954
Rv0287 esxG ESAT-6 like protein EsxG 912 663 ctx neighborhood:663 textmining:752
Rv0289 espG3 ESX-3 secretion-associated protein EspG3 715 597 ctx neighborhood:597
Rv0290 eccD3 ESX-3 secretion system protein EccD 671 579 ctx neighborhood:579
Rv0288 esxH ESAT-6-like protein EsxH 854 578 ctx neighborhood:578 textmining:669
Rv0291 mycP3 membrane-anchored mycosin MycP 547 526 ctx neighborhood:526
Rv0292 eccE3 ESX-3 secretion system protein EccE 560 509 ctx neighborhood:509
Rv0281 S-adenosylmethionine-dependent methyltransferase 490 490 ctx neighborhood:490
Rv0280 PPE3 PPE family protein PPE3 450 416 ctx neighborhood:416
Rv2123 PPE37 PPE family protein PPE37 843 155 textmining:823
Rv1387 PPE20 PPE family protein PPE20 581 71 textmining:568
Rv3873 PPE68 PPE family protein PPE68 656 54 textmining:652

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 family protein PE5
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=2e-20)
  • (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_177710.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26)
  • 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 2B7DA
  • Curated reference: UniProt L7N695 (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 — 25 functional partner(s); context anchor eccB3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0285|PE5
MTLRVVPEGLAAASAAVEALTARLAAAHASAAPVITAVVPPAADPVSLQTAAGFSAQGVEHAVVTAEGVEELGRAGVGVGESGASYLAGDAAAAATYGVVGG