Rv0496 Family assigned · medium auto-curated

H37Rv Rv0496 · MTBC0 - · 328 aa · 586394–587380 (+) · RefSeq NP_215010.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Ppx-GppA (PF02541.23) domain(s); putative function inferred from the domain architecture.

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 P9WHV5 SwissProt · reviewed · Evidence at protein level
UniProt nameExopolyphosphatase 1
EC (curated) EC 3.6.1.11
Curated functionDegradation of inorganic polyphosphates (polyP). Releases orthophosphate processively from the ends of the polyP chain. Prefers short-chain length polyphosphates as substrates. 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 nameppx1
eggNOG descriptionPpx GppA phosphatase
Orthologous groupCOG0248
EC number EC 3.6.1.11, EC 3.6.1.40
KEGG orthology K01524
KEGG pathways map00230
Gene Ontology (11) GO:0003674, GO:0003824, GO:0006793, GO:0008150, GO:0008152, GO:0009987, GO:0016462, GO:0016787, GO:0016817, GO:0016818, GO:0044237

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 0.556 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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 5.4e-952–291 Ppx/GppA phosphatase family

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

Closest characterised functional partner: Rv0497 (transmembrane protein), high confidence from genomic context alone (score 887 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1026 ppx2 hyp hypothetical protein 963 928 database:900 textmining:514
Rv2583c relA bifunctional (p)ppGpp synthase/hydrolase RelA 939 912 database:900
Rv0497 transmembrane protein 887 887 ctx neighborhood:881
Rv0498 hyp hypothetical protein 864 864 ctx neighborhood:863
Rv0499 hyp hypothetical protein 847 847 ctx neighborhood:846
Rv0500 proC pyrroline-5-carboxylate reductase 816 816 ctx neighborhood:815
Rv2984 ppk1 polyphosphate kinase 968 814 ctx cooccurence:432 coexpression:643 textmining:839
Rv0500A DNA-binding protein 717 717 ctx neighborhood:715
Rv0495c hyp hypothetical protein 643 643 ctx neighborhood:639
Rv1629 polA DNA polymerase I 479 480 coexpression:410
Rv0500B Rv0500B, len: 33 aa. Conserved hypothetical protein. Basic protein 18 of the 33 aa are Arg or Lys, with strong similarity to AL079345|SCE68_ 430 430 ctx neighborhood:422
Rv0502 hyp hypothetical protein 417 416
Rv3232c ppk2 polyphosphate kinase 929 414 textmining:885
Rv2603c transcriptional regulator 878 104 textmining:870
Rv3301c phoY1 phosphate transport system transcriptional regulator PhoY 659 82 textmining:645

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): hypothetical protein
  • Pfam (hmmscan --cut_ga): Ppx-GppA PF02541.23 (E=5e-95)
  • (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_215010.3)
  • 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 P9WHV5 (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 — 23 functional partner(s); context anchor Rv0497
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0496|
MVDAHRGGHPTPMSSTKATLRLAEATDSSGKITKRGADKLISTIDEFAKIAISSGCAELMAFATSAVRDAENSEDVLSRVRKETGVELQALRGEDESRLTFLAVRRWYGWSAGRILNLDIGGGSLEVSSGVDEEPEIALSLPLGAGRLTREWLPDDPPGRRRVAMLRDWLDAELAEPSVTVLEAGSPDLAVATSKTFRSLARLTGAAPSMAGPRVKRTLTANGLRQLIAFISRMTAVDRAELEGVSADRAPQIVAGALVAEASMRALSIEAVEICPWALREGLILRKLDSEADGTALIESSSVHTSVRAVGGQPADRNAANRSRGSKP