ppa Resolved · high auto-curated
H37Rv Rv3628 · MTBC0 mtbc0_003845 ·
162 aa · 4091127–4091615 (+) ·
RefSeq NP_218145.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | inorganic pyrophosphatase |
|---|---|
| MTBC0 PGAP re-annotation | inorganic diphosphatase |
| Revised (this work) | Inorganic diphosphatase. Pfam: Pyrophosphatase (PF00719.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WI55
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Inorganic pyrophosphatase |
| EC (curated) |
EC 3.6.1.1
|
| Curated function | Catalyzes the hydrolysis of inorganic pyrophosphate (PPi) forming two phosphate ions..; FUNCTION: Antigen that activates dendritic cells (DCs), increasing their expression of cell surface molecules and augmenting their production of TNF, IL-1beta, IL-6, IL-23 and IL-12p70. Rv3628 mediates these effects by binding to TLR2 and activating downstream MyD88-, MAPK- and NF-kappaB-dependent signaling pathways. Rv3628-stimulated DCs induce the expansion of OVA-specific CD4+ and CD8+ T cells which secrete IFN-gamma and IL-2, and the generation of effector/memory T cells. Thus, Rv3628 polarizes DCs towa. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | ppa |
| eggNOG description | Catalyzes the hydrolysis of inorganic pyrophosphate (PPi) forming two phosphate ions |
| Orthologous group | COG0221 |
| EC number |
EC 3.6.1.1
|
| KEGG orthology |
K01507
|
| KEGG pathways |
map00190
|
| Gene Ontology (29) |
GO:0000287, GO:0003674, GO:0003824, GO:0004427, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006793 +17 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 |
|---|---|---|---|---|
Pyrophosphatase | PF00719.25 | 1.9e-59 | 5–158 | Inorganic pyrophosphatase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hpt (hypoxanthine-guanine phosphoribosyltransferase), high confidence from genomic context alone (score 801 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1307 atpH |
ATP synthase subunit b/delta | 991 | 987 | coexpression:874 database:900 |
Rv1306 atpF |
ATP synthase subunit B | 950 | 945 | coexpression:472 database:900 |
Rv1305 atpE |
ATP synthase subunit C | 953 | 940 | coexpression:417 database:900 |
Rv1309 atpG |
ATP synthase subunit gamma | 947 | 940 | coexpression:414 database:900 |
Rv1308 atpA |
ATP synthase subunit alpha | 950 | 935 | database:900 |
Rv1310 atpD |
ATP synthase subunit beta | 939 | 930 | database:900 |
Rv1311 atpC |
ATP synthase subunit epsilon | 924 | 925 | database:900 |
Rv1304 atpB |
ATP synthase subunit A | 928 | 918 | database:900 |
Rv3232c ppk2 |
polyphosphate kinase | 934 | 904 | database:900 |
Rv2984 ppk1 |
polyphosphate kinase | 944 | 900 | database:900 textmining:462 |
Rv2357c glyS |
glycine--tRNA ligase | 836 | 821 | coexpression:811 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 801 | 801 ctx | neighborhood:774 |
Rv3443c rplM |
50S ribosomal protein L13 | 797 | 798 | coexpression:765 |
Rv2299c htpG |
chaperone protein HtpG | 788 | 776 | coexpression:752 |
Rv3626c hyp |
hypothetical protein | 775 | 775 ctx | neighborhood: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
- Legacy H37Rv annotation: inorganic pyrophosphatase
- MTBC0 PGAP product: inorganic diphosphatase
- Pfam (hmmscan --cut_ga): Pyrophosphatase PF00719.25 (E=2e-59)
- (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 NP_218145.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyrophosphatase (PF00719.25)
- 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
COG0221 - Curated reference: UniProt P9WI55 (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 —
127 functional partner(s); context anchor
hpt - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003845|Rv3628|ppa MQFDVTIEIPKGQRNKYEVDHETGRVRLDRYLYTPMAYPTDYGFIEDTLGDDGDPLDALVLLPQPVFPGVLVAARPVGMFRMVDEHGGDDKVLCVPAGDPRWDHVQDIGDVPAFELDAIKHFFVHYKDLEPGKFVKAADWVDRAEAEAEVQRSVERFKAGTH