PPE49 Family assigned · medium auto-curated

H37Rv Rv3125c · MTBC0 - · 391 aa · 3490476–3491651 (-) · RefSeq YP_177932.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PPE family protein PPE49
MTBC0 PGAP re-annotation
Revised (this work)PPE family protein PPE49. Pfam: PPE (PF00823.26), PPE-SVP (PF12484.14).

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 P9WHY5 SwissProt · reviewed · Inferred from homology
UniProt nameUncharacterized PPE family protein PPE49

UniProt still lists this protein as Uncharacterized PPE family protein PPE49; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category N Cell motility
eggNOG descriptionPPE family
Orthologous groupCOG5651

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 0.544 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 5.92% of strains (8590) · 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
PPEPF00823.26 7.3e-635–167 PPE family
PPE-SVPPF12484.14 9.9e-10293–387 PPE-SVP subfamily C-terminal region

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0894 transcriptional regulator 797 797 coexpression:797
Rv0602c tcrA two component DNA binding transcriptional regulator TcrA 748 748 coexpression:748
Rv0603 hyp hypothetical protein 738 738 coexpression:738
Rv3167c TetR family transcriptional regulator 733 733 coexpression:733
Rv1776c transcriptional regulator 730 730 coexpression:730
Rv3291c lrpA transcriptional regulator LrpA 729 729 coexpression:729
Rv3124 moaR1 transcriptional regulator MoaR 824 703 coexpression:703 textmining:434
Rv1773c transcriptional regulator 703 703 coexpression:703
Rv3111 moaC1 cyclic pyranopterin monophosphate synthase accessory protein 771 651 coexpression:651
Rv3126c hyp hypothetical protein 585 585 ctx neighborhood:501
Rv1359 transcriptional regulator 493 494 coexpression:494
Rv1918c PPE35 PPE family protein PPE35 422 423 coexpression:423
Rv3736 AraC/XylS family transcriptional regulator 415 416 coexpression:416
Rv1675c cmr HTH-type transcriptional regulator Cmr 408 409 coexpression:409
Rv2957 PGL/p-HBAD biosynthesis glycosyltransferase 561 141 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): PPE family protein PPE49
  • Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=7e-63), PPE-SVP PF12484.14 (E=1e-09)
  • (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_177932.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), PPE-SVP (PF12484.14)
  • 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 COG5651
  • Curated reference: UniProt P9WHY5 (SwissProt, reviewed; Inferred from homology)
  • 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 — 21 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3125c|PPE49
MVLGFSWLPPEINSARMFAGAGSGPLFAAASAWEGLAADLWASASSFESVLAALTTGPWTGPASMSMAAAASPYVGWLSTVASQAQLAAIQARAAATAFEAALAATVHPTAVTANRVSLASLIAANVLGQNTPAIAATEFDYLEMWAQDVAAMVGYHAGAKSVAATLAPFSLPPVSLAGLAAQVGTQVAGMATTASAAVTPVVEGAMASVPTVMSGMQSLVSQLPLQHASMLFLPVRILTSPITTLASMARESATRLGPPAGGLAAANTPNPSGAAIPAFKPLGGRELGAGMSAGLGQAQLVGSMSVPPTWQGSIPISMASSAMSGLGVPPNPVALTQAAGAAGGGMPMMLMPMSISGAGAGMPGGLMDRDGAGWHVTQARLTVIPRTGVG