ppk2 Resolved · high auto-curated
H37Rv Rv3232c · MTBC0 - ·
295 aa · 3608870–3609757 (-) ·
RefSeq NP_217749.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyphosphate kinase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polyphosphate kinase. Pfam: PPK2 (PF03976.21). |
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 |
O05877
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GDP-polyphosphate phosphotransferase |
| EC (curated) |
EC 2.7.4.-
|
| Curated function | Uses inorganic polyphosphate (polyP) as a donor to convert GDP to GTP. In addition, modulates nucleotide triphosphate synthesis catalyzed by the nucleoside diphosphate kinase (Ndk) in favor of GTP production over CTP or UTP. Plays an important role in survival of M.tuberculosis in macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | ppk2 |
| eggNOG description | polyphosphate kinase |
| Orthologous group | COG2326 |
| EC number |
EC 2.7.4.1
|
| KEGG orthology |
K22468
|
| KEGG pathways |
map00190, map03018
|
| Gene Ontology (135) |
GO:0000166, GO:0001882, GO:0001883, GO:0003674, GO:0003824, GO:0005488, GO:0005525, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006140 +123 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 | 0.251 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 4 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 |
|---|---|---|---|---|
PPK2 | PF03976.21 | 5.4e-112 | 33–259 | Polyphosphate kinase 2 (PPK2) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ppk1 (polyphosphate kinase), high confidence from genomic context alone (score 954 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2984 ppk1 |
polyphosphate kinase | 994 | 954 ctx | cooccurence:512 database:900 textmining:895 |
Rv3628 ppa |
inorganic pyrophosphatase | 934 | 904 | database:900 |
Rv3231c hyp |
hypothetical protein | 975 | 882 ctx | neighborhood:881 textmining:803 |
Rv3234c tgs3 |
diacyglycerol O-acyltransferase | 860 | 765 ctx | neighborhood:721 textmining:431 |
Rv3233c |
Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 | 856 | 735 ctx | neighborhood:721 textmining:480 |
Rv0213c |
methyltransferase | 691 | 692 | coexpression:692 |
Rv3230c |
stearoyl-CoA 9-desaturase electron transfer protein | 784 | 542 ctx | neighborhood:542 textmining:547 |
Rv2388c hemN |
oxygen-independent coproporphyrinogen III oxidase | 501 | 502 | coexpression:473 |
Rv3235 hyp |
hypothetical protein | 501 | 501 ctx | neighborhood:498 |
Rv1276c hyp |
hypothetical protein | 489 | 490 | |
Rv0408 pta |
phosphate acetyltransferase | 464 | 464 | coexpression:449 |
Rv3229c desA3 |
stearoyl-CoA 9-desaturase | 455 | 451 ctx | neighborhood:448 |
Rv0496 ppx1 hyp |
hypothetical protein | 929 | 414 | textmining:885 |
Rv0545c pitA |
low-affinity inorganic phosphate transporter | 412 | 352 | |
Rv2281 pitB |
phosphate permease | 410 | 350 |
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): polyphosphate kinase
- Pfam (hmmscan --cut_ga): PPK2 PF03976.21 (E=5e-112)
- (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_217749.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPK2 (PF03976.21)
- 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
COG2326 - Curated reference: UniProt O05877 (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 —
22 functional partner(s); context anchor
ppk1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3232c|ppk2 MDIPSVDVSTATNDGASSRAKGHRSAAPGRRKISDAVYQAELFRLQTEFVKLQEWARHSGARLVVIFEGRDGAGKGGAIKRITEYLNPRVARIAALPAPTDRERGQWYYQRYIAHLPAKGEIVLFDRSWYNRAGVEKVMGFCTPQEYVLFLRQTPIFEQMLIDDGILLRKYWFSVSDAEQLRRFKARRNDPVRQWKLSPMDLESVYRWEDYSRAKDEMMVHTDTPVSPWYVVESDIKKHARLNMMAHLLSTIDYADVEKPKVKLPPRPLVSGNYRRPPRELSTYVDDYVATLIAR