ppx2 Resolved · high auto-curated

H37Rv Rv1026 · MTBC0 mtbc0_001102 · 319 aa · 1154356–1155315 (+) · RefSeq NP_215542.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationexopolyphosphatase Ppx2
Revised (this work)Exopolyphosphatase Ppx2. Pfam: Ppx-GppA (PF02541.23).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P96374 SwissProt · reviewed · Evidence at protein level
UniProt nameExopolyphosphatase 2
EC (curated) EC 3.6.1.11
Curated functionDegradation of inorganic polyphosphates (polyP). Releases orthophosphate processively from the ends of the polyP chain. Prefers long-chain length polyphosphates as substrates (By similarity). Can also hydrolyze ATP and ADP substrates, but lacks GTPase activity. Cannot hydrolyze pppGpp to ppGpp.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
P Inorganic ion transport and metabolism
Preferred nameppx2
eggNOG descriptionPFAM Ppx GppA phosphatase
Orthologous groupCOG0248
EC number EC 3.6.1.11, EC 3.6.1.40
KEGG orthology K01524
KEGG pathways map00230
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944

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 0.097 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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)

PfamAccessioni-EvalueResiduesDescription
Ppx-GppAPF02541.23 2.0e-8820–315 Ppx/GppA phosphatase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv1024 (membrane protein), high confidence from genomic context alone (score 871 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1025 hyp hypothetical protein 993 993 ctx neighborhood:881 fusion:899 coexpression:500
Rv0496 ppx1 hyp hypothetical protein 963 928 database:900 textmining:514
Rv2583c relA bifunctional (p)ppGpp synthase/hydrolase RelA 939 912 database:900
Rv1024 membrane protein 909 871 ctx neighborhood:861
Rv1023 eno enolase 862 862 ctx neighborhood:861
Rv2984 ppk1 polyphosphate kinase 965 793 ctx cooccurence:406 coexpression:646 textmining:841
Rv1022 lpqU lipoprotein LpqU 764 765 ctx neighborhood:762
Rv1021 mazG nucleoside triphosphate pyrophosphohydrolase 686 687 ctx neighborhood:682
Rv2538c aroB 3-dehydroquinate synthase 646 646 ctx fusion:608
Rv1020 mfd transcription-repair coupling factor 615 616 ctx neighborhood:610
Rv1629 polA DNA polymerase I 476 477 coexpression:407
Rv1571 hyp hypothetical protein 422 423 coexpression:423
Rv1019 transcriptional regulator 421 422
Rv3232c ppk2 polyphosphate kinase 914 283 textmining:885
Rv3301c phoY1 phosphate transport system transcriptional regulator PhoY 666 98 textmining:646

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: hypothetical protein
  • MTBC0 PGAP product: exopolyphosphatase Ppx2
  • Pfam (hmmscan --cut_ga): Ppx-GppA PF02541.23 (E=2e-88)
  • (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_215542.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ppx-GppA (PF02541.23)
  • 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 COG0248
  • Curated reference: UniProt P96374 (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 — 24 functional partner(s); context anchor Rv1024
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001102|Rv1026|ppx2
MALTRVAAIDCGTNSIRLLIADVGAGLARGELHDVHRETRIVRLGQGVDATGRFAPEAIARTRTALTDYAELLTFHHAERVRMVATSAARDVVNRDVFFAMTADVLGAALPGSAAEVITGAEEAELSFRGAVGELGSAGAPFVVVDLGGGSTEIVLGEHEVVASYSADIGCVRLTERCLHSDPPTLQEVSTARRLVRERLEPALRTVPLELARTWVGLAGTMTTLSALAQSMTAYDAAAIHLSRVPGADLLEVCQRLIGMTRKQRAALAPMHPGRADVIGGGAIVVEELARELRERAGIDQLTVSEHDILDGIALSLAG