PE_PGRS4 Family assigned · medium auto-curated

H37Rv Rv0279c · MTBC0 - · 837 aa · 336560–339073 (-) · RefSeq YP_177708.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE-PGRS family protein PE_PGRS4
MTBC0 PGAP re-annotation
Revised (this work)PE-PGRS family protein PE_PGRS4. 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 L0T4W6 SwissProt · reviewed · Evidence at transcript level
UniProt namePE-PGRS family protein PE_PGRS4

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionacetylesterase activity
Orthologous groupCOG0657
EC number EC 3.1.1.3
KEGG orthology K01046
KEGG pathways map00561, map01100
KEGG modules M00098
Gene Ontology (54) GO:0003674, GO:0003824, GO:0004806, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006950, GO:0008150, GO:0009405, GO:0009605 +42 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)

pN/pS 0.523 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 18 synonymous, 23 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (220) · 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
PEPF00934.26 1.8e-324–94 PE family

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

Closest characterised functional partner: PE_PGRS3 (PE-PGRS family protein PE_PGRS3), medium confidence from genomic context alone (score 423 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0284 eccC3 ESX-3 secretion system protein EccC3 440 440
Rv0278c PE_PGRS3 PE-PGRS family protein PE_PGRS3 430 423 ctx neighborhood:423
Rv0280 PPE3 PPE family protein PPE3 413 413 ctx neighborhood:413
Rv0198c zmp1 zinc metalloprotease 407 407
Rv0277A vapB25 Rv0277A, len: 85 aa. Possible vapB25, antitoxin,part of toxin-antitoxin (TA) operon with Rv0277c, see Arcus et al. 2005. Has in-frame stop c 400 400 ctx neighborhood:400
Rv3213c SOJ/ParA-like protein 704 241 textmining:627
Rv2813 hyp hypothetical protein 520 59 textmining:511
Rv3212 hyp hypothetical protein 803 43 textmining:803
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 512 43 textmining:511
Rv2543 lppA lipoprotein LppA 511 41 textmining:511
Rv1705c PPE22 PPE family protein PPE22 511 41 textmining:511
Rv2544 lppB lipoprotein LppB 511 41 textmining:511
Rv2178c aroG phospho-2-dehydro-3-deoxyheptonate aldolase AroG 438 41 textmining:438
Rv2126c PE_PGRS37 PE-PGRS family protein PE_PGRS37 436 41 textmining:436

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_PGRS4
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=2e-32)
  • (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_177708.1)
  • 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 COG0657
  • Curated reference: UniProt L0T4W6 (SwissProt, reviewed; Evidence at transcript 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 — 14 functional partner(s); context anchor PE_PGRS3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0279c|PE_PGRS4
MSFVIAAPEVIAAAATDLASLESSIAAANAAAAANTTALLAAGADEVSTAVAALFGAHGQAYQALSAQAQAFHAQFVQALTSGGGAYAAAEAAATSPLLAPINEFFLANTGRPLIGNGTNGAPGTGANGGDGGWLIGNGGAGGSGAAGVNGGAGGNGGAGGLIGNGGAGGAGGRASTGTGGAGGAGGAAGMLFGAAGVGGPGGFAAAFGATGGAGGAGGNGGLFADGGVGGAGGATDAGTGGAGGSGGNGGLFGAGGTGGPGGFGIFGGGAGGDGGSGGLFGAGGTGGSGGTSIINVGGNGGAGGDAGMLSLGAAGGAGGSGGSNPDGGGGAGGIGGDGGTLFGSGGAGGVCGLGFDAGGAGGAGGKAGLLIGAGGAGGAGGGSFAGAGGTGGAGGAPGLVGNAGNGGNGGASANGAGAAGGAGGSGVLIGNGGNGGSGGTGAPAGTAGAGGLGGQLLGRDGFNAPASTPLHTLQQQILNAINEPTQALTGRPLIGNGANGTPGTGADGGAGGWLFGNGGNGGHGATGADGGDGGSGGAGGILSGIGGTGGSGGIGTTGQGGTGGTGGAALLIGSGGTGGSGGFGLDTGGAGGRGGDAGLFLGAAGTGGQAALSQNFIGAGGTAGAGGTGGLFANGGAGGAGGFGANGGTGGNGLLFGAGGTGGAGTLGADGGAGGHGGLFGAGGTGGAGGSSGGTFGGNGGSGGNAGLLALGASGGAGGSGGSALNVGGTGGVGGNGGSGGSLFGFGGAGGTGGSSGIGSSGGTGGDGGTAGVFGNGGDGGAGGFGADTGGNSSSVPNAVLIGNGGNGGNGGKAGGTPGAGGTSGLIIGENGLNGL