PPE61 Family assigned · medium auto-curated
H37Rv Rv3532 · MTBC0 - ·
406 aa · 3969343–3970563 (+) ·
RefSeq YP_177984.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE61 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE61. 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 |
P9WHX9
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Uncharacterized PPE family protein PPE61 |
UniProt still lists this protein as Uncharacterized PPE family protein PPE61; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | Polymorphic PE/PPE proteins C terminal |
| 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 | 3.923 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 10 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.73% of strains (1058) · 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 | 1.7e-66 | 4–166 | PPE family |
PPE-SVP | PF12484.14 | 4.9e-17 | 325–402 | PPE-SVP subfamily C-terminal region |
Evidence
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): PPE family protein PPE61
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=2e-66), PPE-SVP PF12484.14 (E=5e-17)
- (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_177984.1)
- 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 P9WHX9 (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)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3532|PPE61 MFMDFAMLPPEVNSTRMYSGPGAGSLWAAAAAWDQVSAELQSAAETYRSVIASLTGWQWLGPSSVRMGAAVTPYVEWLTTTAAQARQTATQITAAATGFEQAFAMTVPPPAIMANRAQVLSLIATNFFGQNTAAIAALETQYAEMWEQDATAMYDYAATSAAARTLTPFTSPQQDTNSAGLPAQSAEVSRATANAGAADGNWLGNLLEEIGILLLPIAPELTPFFLEAGEIVNAIPFPSIVGDEFCLLDGLLAWYATIGSINNINSMGTGIIGAEKNLGILPELGSAAAAAAPPPADIAPAFLAPLTSMAKSLSDGALRGPGEVSAAMRGAGTIGQMSVPPAWKAPAVTTVRAFDATPMTTLPGGDAPAAGVPGLPGMPASGAGRAGVVPRYGVRLTVMTRPLSGG