PE_PGRS16 Family assigned · medium auto-curated

H37Rv Rv0977 · MTBC0 - · 923 aa · 1090373–1093144 (+) · RefSeq YP_177773.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE-PGRS family protein PE_PGRS16
MTBC0 PGAP re-annotation
Revised (this work)PE-PGRS family protein PE_PGRS16. Pfam: PE (PF00934.26), PGRS (PF21526.3), PE-PGRS_C (PF20729.3).

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 Q79FU3 SwissProt · reviewed · Evidence at protein level
UniProt namePE-PGRS family protein PE_PGRS16

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionacetylesterase activity
Orthologous groupCOG0657

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 0.291 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 6 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 9.45% of strains (13721) · 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 8.0e-284–92 PE family
PGRSPF21526.3 2.6e-10121–187 PGRS repeats
PE-PGRS_CPF20729.3 3.6e-91657–920 PE-PGRS C-terminal aspartyl peptidase-like domain

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

Closest characterised functional partner: PPE34 (PPE family protein PPE34), high confidence from genomic context alone (score 771 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2082 hyp hypothetical protein 838 833 ctx cooccurence:773
Rv1917c PPE34 PPE family protein PPE34 771 771 ctx cooccurence:771
Rv3343c PPE54 PPE family protein PPE54 810 770 ctx cooccurence:770
Rv3899c hyp hypothetical protein 778 770 ctx cooccurence:688
Rv0355c PPE8 PPE family protein PPE8 775 770 ctx cooccurence:770
Rv3350c PPE56 PPE family protein PPE56 770 770 ctx cooccurence:770
Rv3347c PPE55 PPE family protein PPE55 770 770 ctx cooccurence:770
Rv1004c membrane protein 772 769 ctx cooccurence:767
Rv0305c PPE6 PPE family protein PPE6 781 767 ctx cooccurence:767
Rv1753c PPE24 PPE family protein PPE24 828 766 ctx cooccurence:766
Rv0304c PPE5 PPE family protein PPE5 765 765 ctx cooccurence:765
Rv3879c espK ESX-1 secretion-associated protein EspK 763 764 ctx cooccurence:723
Rv2209 integral membrane protein 763 763 ctx cooccurence:763
Rv0755c PPE12 PPE family protein PPE12 858 762 ctx cooccurence:762 textmining:431
Rv2356c PPE40 Rv2356c, (MTCY98.25), len: 615 aa. PPE40, Member of Mycobacterium tuberculosis PPE_family, highly similar to others e.g. Q10778|MTCY48.17|YF 760 760 ctx cooccurence:760

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_PGRS16
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=8e-28), PGRS PF21526.3 (E=3e-10), PE-PGRS_C PF20729.3 (E=4e-91)
  • (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_177773.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3), PE-PGRS_C (PF20729.3)
  • 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 Q79FU3 (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 — 131 functional partner(s); context anchor PPE34
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0977|PE_PGRS16
MSFVVTAPPVLASAASDLGGIASMISEANAMAAVRTTALAPAAADEVSAAIAALFSSYARDYQTLSVQVTAFHVQFAQTLTNAGQLYAVVDVGNGVLLKTEQQVLGVINAPTQTLVGRPLIGDGTHGAPGTGQNGGAGGILWGNGGNGGSGAPGQPGGRGGDAGLFGHGGHGGVGGPGIAGAAGTAGLPGGNGANGGSGGIGGAGGAGGNGGLLFGNGGAGGQGGSGGLGGSGGTGGAGMAAGPAGGTGGIGGIGGIGGAGGVGGHGSALFGHGGINGDGGTGGMGGQGGAGGNGWAAEGITVGIGEQGGQGGDGGAGGAGGIGGSAGGIGGSQGAGGHGGDGGQGGAGGSGGVGGGGAGAGGDGGAGGIGGTGGNGSIGGAAGNGGNGGRGGAGGMATAGSDGGNGGGGGNGGVGVGSAGGAGGTGGDGGAAGAGGAPGHGYFQQPAPQGLPIGTGGTGGEGGAGGAGGDGGQGDIGFDGGRGGDGGPGGGGGAGGDGSGTFNAQANNGGDGGAGGVGGAGGTGGTGGVGADGGRGGDSGRGGDGGNAGHGGAAQFSGRGAYGGEGGSGGAGGNAGGAGTGGTAGSGGAGGFGGNGADGGNGGNGGNGGFGGINGTFGTNGAGGTGGLGTLLGGHNGNIGLNGATGGIGSTTLTNATVPLQLVNTTEPVVFISLNGGQMVPVLLDTGSTGLVMDSQFLTQNFGPVIGTGTAGYAGGLTYNYNTYSTTVDFGNGLLTLPTSVNVVTSSSPGTLGNFLSRSGAVGVLGIGPNNGFPGTSSIVTAMPGLLNNGVLIDESAGILQFGPNTLTGGITISGAPISTVAVQIDNGPLQQAPVMFDSGGINGTIPSALASLPSGGFVPAGTTISVYTSDGQTLLYSYTTTATNTPFVTSGGVMNTGHVPFAQQPIYVSYSPTAIGTTTFN