Rv0278c Family assigned · medium auto-curated

H37Rv Rv0278c · MTBC0 - · 957 aa · 333437–336310 (-) · RefSeq YP_177707.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE-PGRS family protein PE_PGRS3
MTBC0 PGAP re-annotation
Revised (this work)PE-PGRS family protein PE_PGRS3. 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 P9WIG3 SwissProt · reviewed · Evidence at protein level
UniProt namePE-PGRS family protein PE_PGRS3
Curated functionThe arginine-rich C-terminal region protrudes from the mycobacterial membrane and mediates M.tuberculosis entry into host epithelial cells. May serve as a bridge between mycobacteria and host cells by interacting with specific host phospholipids and extracting them from host cells, for their direct integration or as a source of phosphate, during phases of TB pathogenesis when M.tuberculosis is short of phosphate supply.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPE-PGRS family
Orthologous groupCOG3391

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 0.293 · purifying
Polymorphic sites (≥ 0.1% of strains) 21 synonymous, 15 missense, 0 nonsense, 4 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 7.68% of strains (11153) · convergent

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 1.2e-334–94 PE family

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

Closest characterised functional partner: 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), high confidence from genomic context alone (score 723 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
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 723 723 ctx neighborhood:723
Rv0277c vapC25 ribonuclease VapC25 660 660 ctx neighborhood:660
Rv0279c PE_PGRS4 PE-PGRS family protein PE_PGRS4 430 423 ctx neighborhood:423
Rv0198c zmp1 zinc metalloprotease 407 407
Rv0931c pknD serine/threonine-protein kinase PknD 413 210
Rv1899c lppD lipoprotein LppD 803 43 textmining:803
Rv0311 hyp hypothetical protein 579 43 textmining:579
Rv0805 cpdA 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA 512 42 textmining:512
Rv3426 PPE58 PPE family protein PPE58 803 41 textmining:803
Rv3344c PE_PGRS49 PE-PGRS family protein PE_PGRS49 656 41 textmining:656
Rv3159c PPE53 PPE family protein PPE53 652 41 textmining:652
Rv0619 galTb Rv0619, (MTCY19H5.02c), len: 181 aa (probable partial CDS). Probable galTb, second part of galactose-1-phosphate uridylyltransferase, highly 510 41 textmining:510
Rv1267c embR transcriptional regulator EmbR 439 41 textmining:439

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_PGRS3
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=1e-33)
  • (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_177707.1)
  • 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 COG3391
  • Curated reference: UniProt P9WIG3 (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 — 13 functional partner(s); context anchor vapB25
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0278c|
MSFVIAAPEVIAAAATDLASLGSSISAANAAAAANTTALMAAGADEVSTAIAALFGAHGQAYQALSAQAQAFHAQFVQALTSGGGAYAAAEAAAVSPLLDPINEFFLANTGRPLIGNGANGAPGTGANGGDGGWLIGNGGAGGSGAAGVNGGAGGNGGAGGNGGAGGLIGNGGAGGAGGVASSGIGGSGGAGGNAMLFGAGGAGGAGGGVVALTGGAGGAGGAGGNAGLLFGAAGVGGAGGFTNGSALGGAGGAGGAGGLFATGGVGGSGGAGSSGGAGGAGGAGGLFGAGGTGGHGGFADSSFGGVGGAGGAGGLFGAGGEGGSGGHSLVAGGDGGAGGNAGMLALGAAGGAGGIGGDGGTLTAGGIGGAGGAGGNAGLLFGSGGSGGAGGFGFADGGQGGPGGNAGTVFGSGGAGGNGGVGQGFAGGIGGAGGTPGLIGNGGNGGNGGASAVTGGNGGIGGTGVLIGNGGNGGSGGIGAGKAGVGGVSGLLLGLDGFNAPASTSPLHTLQQNVLNVVNEPFQTLTGRPLIGNGANGTPGTGADGGAGGWLFGNGANGTPGTGAAGGAGGWLFGNGGNGGHGATNTAATATGGAGGAGGILFGTGGNGGTGGIATGAGGIGGAGGAGGVSLLIGSGGTGGNGGNSIGVAGIGGAGGRGGDAGLLFGAAGTGGHGAAGGVPAGVGGAGGNGGLFANGGAGGAGGFNAAGGNGGNGGLFGTGGTGGAGTNFGAGGNGGNGGLFGAGGTGGAAGSGGSGITTGGGGHGGNAGLLSLGASGGAGGSGGASSLAGGAGGTGGNGALLFGFRGAGGAGGHGGAALTSIQQGGAGGAGGNGGLLFGSAGAGGAGGSGANALGAGTGGTGGDGGHAGVFGNGGDGGCRRVWRRYRRQRWCRRQRRADRQRRQRRQRRQSRGHARCRRHRRAAARRERTQRLAIAGRPATTRGVEGISCSPQMMP