PE_PGRS59 Family assigned · medium auto-curated

H37Rv Rv3595c · MTBC0 - · 439 aa · 4036731–4038050 (-) · RefSeq YP_177994.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE-PGRS family protein PE_PGRS59
MTBC0 PGAP re-annotation
Revised (this work)PE-PGRS family protein PE_PGRS59. Pfam: PE (PF00934.26), PGRS (PF21526.3).

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 Q6MWV6 TrEMBL · unreviewed · Predicted
UniProt namePE-PGRS family protein PE_PGRS59

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionPE-PGRS family
Orthologous groupCOG0657
Gene Ontology (46) GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0006950, GO:0008150, GO:0009405, GO:0009605, GO:0009607, GO:0009628, GO:0009987 +34 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) pseudogene candidate

pN/pS 0.403 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 6.23% of strains (9040) · 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 1.3e-354–94 PE family
PGRSPF21526.3 1.5e-14116–185 PGRS repeats

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

Closest characterised functional partner: clpC1 (ATP-dependent protease ATP-binding subunit ClpC), medium confidence from genomic context alone (score 519 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3596c clpC1 ATP-dependent protease ATP-binding subunit ClpC 519 519 ctx neighborhood:519
Rv0198c zmp1 zinc metalloprotease 407 407
Rv1146 mmpL13b transmembrane transport protein 525 71 textmining:510
Rv0878c PPE13 PPE family protein PPE13 611 41 textmining:611
Rv0388c PPE9 Rv0388c, (MTV036.23c), len: 180 aa. PPE9, Member of the Mycobacterium tuberculosis PPE family, highly similar to others e.g. MTCY10G2_10|Z92 515 41 textmining:515
Rv0354c PPE7 PPE family protein PPE7 511 41 textmining:511

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_PGRS59
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=1e-35), PGRS PF21526.3 (E=1e-14)
  • (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_177994.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3)
  • 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 Q6MWV6 (TrEMBL, unreviewed; Predicted)
  • 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 — 6 functional partner(s); context anchor clpC1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3595c|PE_PGRS59
MSFVIAVPEFLSAAATDLANLGSTISAANAAASIPTTGVLAAGADDVSAAIAALFGAHAQAYQTISAQAATFHAQFVQTLSAGAGAYANAEAANVQQSLLNAINAPTQALLGRPLIGDGADGTAPGQNGGAGGLLYGNGGNGAAGVNAGIAGGSGGAAGLIGNGGSGGAGGAGAAGGSGGQGGLLYGNGGAGGNGGAATIPGGNGGAGGAGGNAWLFGNGGAGGLGAAGAAGAAGVNPLTVPAGQGSMGNNGEPGGPGQPGTEFGQTGGTGGTGGTGLSVGGTGGTGGTGGTGGAGGSGGRGGLLVGDGGAGGIGGTGGEGGIGARGGTGGQGGMGGAGQPGVGGDAGDGGNGGIGGDGGAGGDGGAGGAGGAGGLFGVSGSSGLGGAAGSGGNGGGGGEPGVAGSPGVGPAGRGGDGNLGQFGPEGAPGQPGQPGQPG