PPE8 Family assigned · medium auto-curated
H37Rv Rv0355c · MTBC0 - ·
3300 aa · 424777–434679 (-) ·
RefSeq YP_177721.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE8 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE8. Pfam: PPE (PF00823.26), Pentapeptide_2 (PF01469.25). |
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 |
I6Y7L4
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | PPE family protein PPE8 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | Pentapeptide repeats (8 copies) |
| Orthologous group | COG1357 |
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 | 0.331 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 115 synonymous, 117 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 29.76% of strains (43216) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PPE | PF00823.26 | 1.0e-60 | 3–166 | PPE family |
Pentapeptide_2 | PF01469.25 | 2.6e-10 | 1166–1204 | Pentapeptide repeats (8 copies) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: csm5 (CRISPR type III-associated RAMP protein Csm5), high confidence from genomic context alone (score 776 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0304c PPE5 |
PPE family protein PPE5 | 859 | 860 | coexpression:850 |
Rv3347c PPE55 |
PPE family protein PPE55 | 830 | 820 | coexpression:780 |
Rv0305c PPE6 |
PPE family protein PPE6 | 791 | 790 | coexpression:770 |
Rv3903c cpnT hyp |
hypothetical protein | 786 | 787 ctx | cooccurence:759 |
Rv2082 hyp |
hypothetical protein | 776 | 777 ctx | cooccurence:774 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 776 | 776 ctx | cooccurence:773 |
Rv2209 |
integral membrane protein | 775 | 776 ctx | cooccurence:774 |
Rv0341 iniB |
isoniazid inducible protein IniB | 775 | 775 ctx | cooccurence:774 |
Rv2293c hyp |
hypothetical protein | 775 | 775 ctx | cooccurence:772 |
Rv3864 espE |
ESX-1 secretion-associated protein EspE | 774 | 775 ctx | cooccurence:772 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 774 | 774 ctx | cooccurence:774 |
Rv2954c hyp |
hypothetical protein | 774 | 774 ctx | cooccurence:773 |
Rv1004c |
membrane protein | 774 | 774 ctx | cooccurence:774 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 774 | 774 ctx | cooccurence:774 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 774 | 774 ctx | cooccurence:774 |
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 PPE8
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-60), Pentapeptide_2 PF01469.25 (E=3e-10)
- (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_177721.2)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), Pentapeptide_2 (PF01469.25)
- 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
COG1357 - Curated reference: UniProt I6Y7L4 (TrEMBL, unreviewed; 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 —
141 functional partner(s); context anchor
csm5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0355c|PPE8 MSFAVLPPEINSARLYVGAGLAPMLDAAAAWDGLADELGSAAASFSAVTAGLAGSSWLGAASTAMTGAAAPYLGWLSAAAAQAQQAATQTRLAAAAFEAALAATVHPAIISANRALFVSLVVSNLLGQNAPAIAATEAAYEQMWAQDVAAMFGYHAGASAAVSALTPFGQALPTVAGGGALVSAAAAQVTTRVFRNLGLANVGEGNVGNGNVGNFNLGSANIGNGNIGSGNIGSSNIGFGNVGPGLTAALNNIGFGNTGSNNIGFGNTGSNNIGFGNTGDGNRGIGLTGSGLLGFGGLNSGTGNIGLFNSGTGNVGIGNSGTGNWGIGNSGNSYNTGFGNSGDANTGFFNSGIANTGVGNAGNYNTGSYNPGNSNTGGFNMGQYNTGYLNSGNYNTGLANSGNVNTGAFITGNFNNGFLWRGDHQGLIFGSPGFFNSTSAPSSGFFNSGAGSASGFLNSGANNSGFFNSSSGAIGNSGLANAGVLVSGVINSGNTVSGLFNMSLVAITTPALISGFFNTGSNMSGFFGGPPVFNLGLANRGVVNILGNANIGNYNILGSGNVGDFNILGSGNLGSQNILGSGNVGSFNIGSGNIGVFNVGSGSLGNYNIGSGNLGIYNIGFGNVGDYNVGFGNAGDFNQGFANTGNNNIGFANTGNNNIGIGLSGDNQQGFNIASGWNSGTGNSGLFNSGTNNVGIFNAGTGNVGIANSGTGNWGIGNPGTDNTGILNAGSYNTGILNAGDFNTGFYNTGSYNTGGFNVGNTNTGNFNVGDTNTGSYNPGDTNTGFFNPGNVNTGAFDTGDFNNGFLVAGDNQGQIAIDLSVTTPFIPINEQMVIDVHNVMTFGGNMITVTEASTVFPQTFYLSGLFFFGPVNLSASTLTVPTITLTIGGPTVTVPISIVGALESRTITFLKIDPAPGIGNSTTNPSSGFFNSGTGGTSGFQNVGGGSSGVWNSGLSSAIGNSGFQNLGSLQSGWANLGNSVSGFFNTSTVNLSTPANVSGLNNIGTNLSGVFRGPTGTIFNAGLANLGQLNIGSANLGDFNLGSGNVGSFNVFSGNQGSYNIGPANLGNYNIGFANLGNYNIGFGNAGDFNQGFANTGNNNIGFANTGNNNIGIGLSGDNQQGFNFAGGWNSGTANIGLFNSGTNNVGIGNSGTGNWGIGNSGSGNTGIGNTGSTNTGFFNTGIVNTGVANAGSYNTGWYNTGDTNTGIANLGDFNTGFYNTGNFSTGFANQGDIATGAFITGDMGNGAFWRGDQQGLFSAGYRVHVPEIPAHVTVEVPVNIPITASFTNTVYSGITLEQINFGFTIDIAGIPLLAGAISKAVLPPITGTGPAITVNIGDPGGSTAIRIPATASVGPFDVTFVNIAATTGFFNATTDPSSGFFNGGPGTVSGIANIGANISGFQNVANSATSGFNNYGSLQSGLANLGDTVSGVFNTGIGAPANVSGMFNIGSNLAGFFHDQATGMSMFNLGLGNIGQFNVGFSNVGDSNAGLANIGSFNLGSGNLGSFNVFGGNQGSYNIGPANLGNYNIGLGNLGSYNFGFGNAGDFNLGFANTGNNNIGFANTGNNNIGIGLSGDNQQGFNFAGGWNSGSGNSGLFNSGTNNIGLFNSGTGNIGIGNSGTGNWGIANTGDTNTGIFNTGDVNTGLLNAGNVNTGIFNTGHYNTGSFNAGSFNTAGFNPGSYNTGYLNTGSYNTGLANSGDVNTGGFITGNYSNGFWWRGDYQGLAGISQTITVPDTAVPVKLHVPIFLDIPVTGTLGTFTVHGFRFPEITGDIFLIGIPFNAATLDAFSFPNISIVLPNIGINLGSGPDPLIDIAGTGGLLPIKIPLIDIPAAPGFGNSTTTPSSGFFNAGTGTVSGVGNVGSNSSGFFNLTSGSSGISGVQNFGELISGGFNFGNTVSGLVNASTLGLSMPANLSGGGNVGATVAGFVNNTQILNLGFGNVGSGNVGHGNIGDSNVGLGNLGNANVGHGNIGSFNVFSGNRGSYNIGPANLGNYNIGLGNLGSYNFGFGNAGDFNLGFANSGSNNIGFANTGNNNIGIGLSGHNQQGFGSWNSGTANTGLFNSGTNNIGLFNSGTGNIGIGNSGIGNTGIGNPGVGNTGLGNSGTGNWGLWNPGTGNMGVANVGTYNTGGYNVGSTNTGIANVGIANTGSYNTGSTNTGSFNDGDFNTGFYNTGDYNTGFYNTGDVNTGAFIGGNFSNGAFWQSDHQGQWGAHYAITVPQIPLLNFSLNIPVNIPIHLDFGTLAVNGFQIPAITLRALGVTHFSVGPIIVPRIAGTLPVIDINIGDPGGSSSIPITITSGAGPVVIPLLDIPPAPGFGNSTTGPSSGFFNSGTGSSSGFGNVGANNSGFWNTAFAGIGNSGLQNFGSLQSGWANLGNTVSGFYNTSAADFATPANLSGLSNVGADLTGVLRGPNGSTFNAGLANLGQFNVGSANLGSANLGSANLGSANLGNSNVGFGNIGNANIGGANIGDFNVGIANTGPGLTAAVNNIGIGNTGNYNIGVGNTGNYNIGFGNTGNNNIGIGLSGDNQIGFGPLNAGIANMGLFNLGDNNFGMANAGNFNQGIANTGNNNIGLFNTGNNNVGIGLTGDGLSGFSSLNSGAGNTGFFNSGTANTGLFNSGTGNTGLFNSGTGNVGIGNMGTGGFGVGLSGDSQVGIGGTNSGSFNIGLFNSGTGNVGIGNSGTGNVGIGNTGTGNTGIGNSGNYNTGLLNAGLVNTGIANPGNHNTGLFNIGTFNTGIANPGHYNTGSYNTGSYNTGMANAGDYGTGAFITGSMNNGLLWRADRQGLLAANYTITIERPAAFLNVDIPVNIPITGDITNVSIPAITFPRIDASGSVDIGILSGTVLAPVGPITLHGGDASAPLDTPIEIDFGPSPAINLNIGKPDGSTVINIVGGAGAGPISIPIIDLRPAPGFFNATTGPSSGFLNWGAGSASGLLNFGNNSGLYNFATSSMGNSGFQNYGSLQSGWANLGNSISGIYNTGLGAPANVSGLLNIGTNLAGWLQNGPTETTFSVGLANLGFWNLGSANIGNYNLGSANIGVYNLGSANIGDFNLGSANIGDFNLGSANIGSSNIGFGNVGPGLTAAIGNIGFGNTGNGNIGIGNTGTGNIGFGNTGNGNIGIGLTGDTMTGFGGWNSGTGNIGLFNSGTGNIGFGNSGTGNWGIGNSGDYNTGIGNTGSTNSGFFNTGLVNTGIGNSGDYNTGLFNAGNTNTGSFNPGDYNTGGFNPGNYNTGYFNPGNSNTGIANSGDVNTGAFNSGNYSNGFFWRGDYQGLGGFAYQSAVSEIPWSYDRFQH