PE_PGRS49 Family assigned · low auto-curated

H37Rv Rv3344c · MTBC0 - · 338 aa · 3736984–3738000 (-) · RefSeq YP_177961.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE-PGRS family protein PE_PGRS49
MTBC0 PGAP re-annotation
Revised (this work)PE-PGRS family protein PE_PGRS49.

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 L0TFC2 TrEMBL · unreviewed · Evidence at protein level
UniProt namePE-PGRS family protein PE_PGRS49

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.55 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (650) · 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: PE_PGRS50 (PE-PGRS family protein PE_PGRS50), high confidence from genomic context alone (score 773 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3345c PE_PGRS50 PE-PGRS family protein PE_PGRS50 830 773 ctx neighborhood:773
Rv3343c PPE54 PPE family protein PPE54 706 623 ctx neighborhood:623
Rv1087 PE_PGRS21 PE-PGRS family protein PE_PGRS21 804 41 textmining:804
Rv1067c PE_PGRS19 PE-PGRS family protein PE_PGRS19 704 41 textmining:704
Rv3426 PPE58 PPE family protein PPE58 679 41 textmining:679
Rv2519 PE26 PE family protein PE26 657 41 textmining:657
Rv0278c PE_PGRS3 PE-PGRS family protein PE_PGRS3 656 41 textmining:656
Rv3652 PE_PGRS60 PE-PGRS family-related protein PE_PGRS60 651 41 textmining:651
Rv1899c lppD lipoprotein LppD 650 41 textmining:650
Rv1089 PE10 PE family protein PE10; Together with PE9, induces macrophage apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Interac 630 41 textmining:630
Rv0747 PE_PGRS10 PE-PGRS family protein PE_PGRS10 630 41 textmining:630
Rv3512 PE_PGRS56 PE-PGRS family protein PE_PGRS56 626 41 textmining:626
Rv2099c PE21 Rv2099c, (MTCY49.39c), len: 58 aa. PE21, Member of the Mycobacterium tuberculosis PE family (see Brennan and Delogu, 2002); 5'-end of Rv2098 546 41 textmining:546
Rv3018A PE27A Rv3018A, len: 28 aa. PE27A, Member of Mycobacterium tuberculosis PE family (see Brennan and Delogu, 2002), most similar to Rv0285 (102 aa), 541 41 textmining:541
Rv1066 hyp hypothetical protein 510 41 textmining:510

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_PGRS49
  • (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_177961.2)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt L0TFC2 (TrEMBL, unreviewed; 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 — 19 functional partner(s); context anchor PE_PGRS50
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3344c|PE_PGRS49
MLGGKGGDGGNGDHGGPATNPGSGSRGGAGGSGGNGGAGGNATGSGGKGGAGGNGGDGSFGATSGPASIGVTGAPGGNGGKGGAGGSNPNGSGGDGGKGGNGGAGGNGGSIGANSGIVGGSGGAGGAGGAGGNGSLSSGEGGKGGDGGHGGDGVGGNSSVTQGGSGGGGGAGGAGGSGFFGGKGGFGGDGGQGGPNGGGTVGTVAGGGGNGGVGGRGGDGVFAGAGGQGGLGGQGGNGGGSTGGNGGLGGAGGGGGNAPDGGFGGNGGKGGQGGIGGGTQSATGLGGDGGDGGDGGNGGNSGAKAGGAGGKGQAGQPNSGTEPGFGGDGGLGGAGATP