PPE37 Family assigned · medium auto-curated
H37Rv Rv2123 · MTBC0 - ·
473 aa · 2381071–2382492 (+) ·
RefSeq YP_177861.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE37 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE37. Pfam: PPE (PF00823.26), PPE-PPW (PF18878.6). |
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 |
Q79FH3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE37 |
| Curated function | Essential for efficient heme-iron acquisition (HIA). Binds iron. Strains with a functional PPE37 can utilize low concentrations of hemin very efficiently in broth and on agar plates. During infection, might interfere with the pro-inflammatory cytokine response in infected macrophages..; FUNCTION: In vitro, incubation of the protein in the presence of M.tuberculosis proteases leads to the cleavage of PPE37 into two segments, the N- and C-terminal segments. Transfection of human monocytic THP-1 cell lines with the N-terminal segment leads to the proliferation and differentiation of THP-1 cells i. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | PPE family |
| Orthologous group | COG5651 |
| Gene Ontology (16) |
GO:0008150, GO:0009605, GO:0009607, GO:0043207, GO:0044403, GO:0044419, GO:0050896, GO:0051701, GO:0051704, GO:0051707, GO:0052173, GO:0052200 +4 more
|
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 | 1.175 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 16 missense, 0 nonsense, 4 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 25.75% of strains (37396) · convergent |
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 | 1.1e-56 | 5–168 | PPE family |
PPE-PPW | PF18878.6 | 1.2e-08 | 424–469 | PPE-PPW subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hisE (phosphoribosyl-ATP pyrophosphatase), medium confidence from genomic context alone (score 552 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3839 hyp |
hypothetical protein | 886 | 806 | coexpression:806 textmining:440 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 826 | 806 | coexpression:806 |
Rv2122c hisE |
phosphoribosyl-ATP pyrophosphatase | 727 | 552 ctx | neighborhood:550 textmining:417 |
Rv2121c hisG |
ATP phosphoribosyltransferase | 550 | 550 ctx | neighborhood:550 |
Rv2120c |
integral membrane protein | 781 | 418 ctx | neighborhood:418 textmining:640 |
Rv1348 irtA |
iron ABC transporter ATP-binding protein/permease IrtA | 404 | 168 | |
Rv0285 PE5 |
PE family protein PE5 | 843 | 155 | textmining:823 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 482 | 152 | textmining:416 |
Rv0287 esxG |
ESAT-6 like protein EsxG | 483 | 115 | textmining:441 |
Rv3402c hyp |
hypothetical protein | 548 | 110 | textmining:514 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 497 | 103 | textmining:463 |
Rv0292 eccE3 |
ESX-3 secretion system protein EccE | 426 | 79 | textmining:403 |
Rv2108 PPE36 |
PPE family protein PPE36 | 409 | 51 | textmining:403 |
Rv3841 bfrB |
bacterioferritin BfrB | 437 | 50 | textmining:432 |
Rv1386 PE15 |
PE family protein PE15 | 437 | 46 | textmining:434 |
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 PPE37
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-56), PPE-PPW PF18878.6 (E=1e-08)
- (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_177861.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), PPE-PPW (PF18878.6)
- 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 Q79FH3 (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 —
16 functional partner(s); context anchor
hisE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2123|PPE37 MTFPMWFAVPPEVPSAWLSTGMGPGPLLAAARAWHALAAQYTEIATELASVLAAVQASSWQGPSADRFVVAHQPFRYWLTHAATVATAAAAAHETAAAGYTSALGGMPTLAELAANHAMHGALVTTNFFGVNTIPIALNEADYLRMWIQAATVMSHYQAVAHESVAATPSTPPAPQIVTSAASSAASSSFPDPTKLILQLLKDFLELLRYLAVELLPGPLGDLIAQVLDWFISFVSGPVFTFLAYLVLDPLIYFGPFAPLTSPVLLPAGLTGLAGLGAVSGPAGPMVERVHSDGPSRQSWPAATGVTLVGTNPAALVTTPAPAPTTSAAPTAPSTPGSSAAQGLYAVGGPDGEGFNPIAKTTALAGVTTDAAAPAAKLPGDQAQSSASKATRLRRRLRQHRFEFLADDGRLTMPNTPEMADVAAGNRGLDALGFAGTIPKSAPGSATGLTHLGGGFADVLSQPMLPHTWDGSD