PPE44 Family assigned · medium auto-curated
H37Rv Rv2770c · MTBC0 - ·
382 aa · 3079309–3080457 (-) ·
RefSeq YP_177677.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE44 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE44. 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 |
P9WHZ3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE44 |
| Curated function | Virulence factor that modulates host innate immune response. Induces the production of the pro-inflammatory cytokines IL-6 and IL-12p40 in macrophages via NF-kappa-B, ERK1/2 and p38 signaling axis. Can enhance M.smegmatis survival within macrophages and under stresses such as H(2)O(2), SDS, diamide exposure and low pH condition. Promotes the death of macrophage by apoptosis in the later stage of infection. |
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 | 0.372 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 10 missense, 0 nonsense, 0 frameshift |
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 | 6.5e-59 | 2–164 | PPE family |
PPE-SVP | PF12484.14 | 3.1e-17 | 300–378 | PPE-SVP subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PE27 (PE family protein PE27), medium confidence from genomic context alone (score 447 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1040c PE8 |
PE family protein PE8 | 904 | 899 | experimental:891 |
Rv1794 espG5 hyp |
hypothetical protein | 891 | 891 | experimental:891 |
Rv2771c hyp |
hypothetical protein | 513 | 512 ctx | neighborhood:506 |
Rv2769c PE27 |
PE family protein PE27 | 489 | 447 ctx | neighborhood:447 |
Rv2336 hyp |
hypothetical protein | 870 | 47 | textmining:870 |
Rv1345 mbtM |
long-chain-fatty-acid--ACP ligase MbtM | 659 | 44 | textmining:658 |
Rv0288 esxH |
ESAT-6-like protein EsxH | 628 | 44 | textmining:627 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 805 | 43 | textmining:805 |
Rv1320c |
adenylate cyclase | 753 | 41 | textmining:753 |
Rv1806 PE20 |
PE family protein PE20 | 528 | 41 | textmining:529 |
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 PPE44
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=7e-59), PPE-SVP PF12484.14 (E=3e-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_177677.1)
- 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 P9WHZ3 (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 —
10 functional partner(s); context anchor
PE27 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2770c|PPE44 MDFGALPPEVNSARMYGGAGAADLLAAAAAWNGIAVEVSTAASSVGSVITRLSTEHWMGPASLSMAAAVQPYLVWLTCTAESSALAAAQAMASAAAFETAFALTVPPAEVVANRALLAELTATNILGQNVSAIAATEARYGEMWAQDASAMYGYAAASAVAARLNPLTRPSHITNPAGLAHQAAAVGQAGASAFARQVGLSHLISDVADAVLSFASPVMSAADTGLEAVRQFLNLDVPLFVESAFHGLGGVADFATAAIGNMTLLADAMGTVGGAAPGGGAAAAVAHAVAPAGVGGTALTADLGNASVVGRLSVPASWSTAAPATAAGAALDGTGWAVPEEDGPIAVMPPAPGMVVAANSVGADSGPRYGVKPIVMPKHGLF