PPE6 Family assigned · medium auto-curated
H37Rv Rv0305c · MTBC0 - ·
963 aa · 372820–375711 (-) ·
RefSeq YP_177715.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE6 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE6. 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 |
Q6MX48
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | PPE family protein PPE6 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | Pentapeptide repeats (8 copies) |
| Orthologous group | COG5651 |
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 | 0.75 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 17 missense, 1 nonsense, 4 frameshift |
| Disruption | 5 distinct premature-stop/frameshift site(s); most common in 96.71% of strains (140430) · reference-fixed |
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 | 1.7e-60 | 2–165 | PPE family |
Pentapeptide_2 | PF01469.25 | 3.8e-11 | 771–808 | Pentapeptide repeats (8 copies) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE5 (PPE family protein PPE5), high confidence from genomic context alone (score 947 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0304c PPE5 |
PPE family protein PPE5 | 950 | 947 ctx | neighborhood:618 coexpression:853 |
Rv0355c PPE8 |
PPE family protein PPE8 | 791 | 790 | coexpression:770 |
Rv3533c PPE62 |
PPE family protein PPE62 | 784 | 785 | coexpression:761 |
Rv3903c cpnT hyp |
hypothetical protein | 782 | 782 ctx | cooccurence:755 |
Rv1548c PPE21 |
PPE family protein PPE21 | 776 | 776 | coexpression:730 |
Rv2082 hyp |
hypothetical protein | 775 | 776 ctx | cooccurence:773 |
Rv1004c |
membrane protein | 774 | 775 ctx | cooccurence:774 |
Rv2209 |
integral membrane protein | 774 | 774 ctx | cooccurence:773 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 774 | 774 ctx | cooccurence:774 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 773 | 773 ctx | cooccurence:773 |
Rv2853 PE_PGRS48 |
PE-PGRS family protein PE_PGRS48 | 773 | 773 ctx | cooccurence:773 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 773 | 773 ctx | cooccurence:773 |
Rv1243c PE_PGRS23 |
PE-PGRS family protein PE_PGRS23 | 773 | 773 ctx | cooccurence:773 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 773 | 773 ctx | cooccurence:773 |
Rv0124 PE_PGRS2 |
PE-PGRS family protein PE_PGRS2 | 773 | 773 ctx | cooccurence:773 |
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 PPE6
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=2e-60), Pentapeptide_2 PF01469.25 (E=4e-11)
- (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_177715.1)
- 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
COG5651 - Curated reference: UniProt Q6MX48 (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 —
122 functional partner(s); context anchor
PPE5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0305c|PPE6 MDFVVSAPEVNSLRMYLGAGSGPMLAAAAAWDGLADELAVAASWFGSVTSGLADAAWRGPAAVAMARAVAPYLGWLISATAQAEQAAAQARVAVATFEAARAATVHPAIVAANRAVLVSLVSSNLLGFNAPAIAATEAAYERMWAQDVAAMVGYHAGASAAVSALMPFTQQLKKLAGLSERLTSAAAAAAGPPSAAGFNLGLANVGANNVGNGNVGVFNVGFGNLGSYNLGFANLGSDNLGLANLGGHNIGFANTGSNNVGFGNTGSNNVGIGLTGNGQIGFGSFNSGSHNIGLFNSGSGNVGLFNSGTGNFGIGNSGTGNFGLGNTGSTNTGWFNTGDVNTGGFNPGSYNTGNFNTGNYNTGSFNAGNYNTGYFNTGDYNTGVANTGNVNTGAFIAGNYSNGVLWRGDYQGLIGADIALEIPAIPINAQLFSMPIHQVMVMPGSVMTIPGMRLPFTSIVPFVVYYGPVELPQSTLTLPTVTITVGGPTTTIDGNLTGMVGGVSIPLIKIPAAPGFGNSTTSPSSGFFNAGAGTASGFGNFGGGASGFWNLASATSGLSGFGNVGALGSGVANVGNTISGLYNTSTSNLATPAFNSGLLHHSVGTMTLNFGLANVGGNNVGGANAGIFNVGLANLGDYNIGFGNLGGDNLGFAHAGSYNIGFANTGSNNLGFANTGDNNIGFANIGSNNIGIGLTGSGQIGFGSLNSGSHNIGLFNSGDGNIGLFNSGSGNFGIGNAGTGNWGIGNSGAGNFGIGNAGSTNTGLFNSGDLNTGSLNPGSYNTGSVNTGSVNTGGFNAGNYNTGYFNTGDLQHRHGEHRQYQHRRFHLRQPQQRPSVAGRQPGSDRPRHRRRHSRNPDCERRREYPDSHTDHRQLHGHRIQRARSSTEHSRHCYFFRTRRYRPLHRPSDTDNRSHTCGHGGWTHYRDQYRRHCGRRRHQHPDYPYSSDSRLRQLDRRTVVGLLQ