rdgB Family assigned · medium auto-curated

H37Rv Rv1341 · MTBC0 mtbc0_001438 · 204 aa · 1518275–1518889 (+) · RefSeq NP_215857.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)non-canonical purine NTP pyrophosphatase
MTBC0 PGAP re-annotationRdgB/HAM1 family non-canonical purine NTP pyrophosphatase
Revised (this work)RdgB/HAM1 family non-canonical purine NTP pyrophosphatase. Pfam: Ham1p_like (PF01725.22).

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

Curated reference (UniProt)

UniProt P9WMR7 SwissProt · reviewed · Evidence at protein level
UniProt namedITP/XTP pyrophosphatase
EC (curated) EC 3.6.1.66
Curated functionPyrophosphatase that catalyzes the hydrolysis of nucleoside triphosphates to their monophosphate derivatives, with a high preference for the non-canonical purine nucleotides XTP (xanthosine triphosphate), dITP (deoxyinosine triphosphate) and ITP. Seems to function as a house-cleaning enzyme that removes non-canonical purine nucleotides from the nucleotide pool, thus preventing their incorporation into DNA/RNA and avoiding chromosomal lesions.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namerdgB
eggNOG descriptionPyrophosphatase that catalyzes the hydrolysis of nucleoside triphosphates to their monophosphate derivatives, with a high preference for the non-canonical purine nucleotides XTP (xanthosine triphosphate), dITP (deoxyinosine triphosphate) and ITP. Seems to function as a house-cleaning enzyme that removes non-canonical purine nucleotides from the nucleotide pool, thus preventing their incorporation into DNA RNA and avoiding chromosomal lesions
Orthologous groupCOG0127
EC number EC 3.6.1.66
KEGG orthology K02428
KEGG pathways map00230
Gene Ontology (55) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006139, GO:0006725, GO:0006753, GO:0006793, GO:0006796 +43 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 0.195 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (352) · clonal

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
Ham1p_likePF01725.22 6.5e-597–195 Ham1 family

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

Closest characterised functional partner: rphA (ribonuclease PH), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1340 rphA ribonuclease PH 993 994 ctx neighborhood:825 fusion:900 coexpression:678
Rv3396c guaA GMP synthase 975 963 ctx cooccurence:409 database:900
Rv1338 murI glutamate racemase 960 960 ctx neighborhood:632 fusion:890
Rv2445c ndkA nucleoside diphosphate kinase 938 931 database:900
Rv3411c guaB2 inosine-5'-monophosphate dehydrogenase 935 928 database:900
Rv1843c guaB1 inosine-5'-monophosphate dehydrogenase 934 927 database:900
Rv3410c guaB3 oxidoreductase 926 919 database:900
Rv1021 mazG nucleoside triphosphate pyrophosphohydrolase 916 916 database:900
Rv3624c hpt hypoxanthine-guanine phosphoribosyltransferase 911 905 database:900
Rv1339 hyp hypothetical protein 821 821 ctx neighborhood:808
Rv1336 cysM O-phosphoserine sulfhydrylase 813 813 ctx neighborhood:780
Rv1335 cysO sulfur carrier protein CysO 785 785 ctx neighborhood:777
Rv1334 mec [CysO 773 774 ctx neighborhood:758
Rv0639 nusG transcription termination/antitermination protein NusG 767 767 coexpression:767
Rv1333 hydrolase 761 762 ctx neighborhood:758

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: non-canonical purine NTP pyrophosphatase
  • MTBC0 PGAP product: RdgB/HAM1 family non-canonical purine NTP pyrophosphatase
  • Pfam (hmmscan --cut_ga): Ham1p_like PF01725.22 (E=7e-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_215857.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ham1p_like (PF01725.22)
  • 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 COG0127
  • Curated reference: UniProt P9WMR7 (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 — 68 functional partner(s); context anchor rphA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001438|Rv1341|rdgB
MALVTKLLVASRNRKKLAELRRVLDGAGLSGLTLLSLGDVSPLPETPETGVTFEDNALAKARDAFSATGLASVADDSGLEVAALGGMPGVLSARWSGRYGDDAANTALLLAQLCDVPDERRGAAFVSACALVSGSGEVVVRGEWPGTIAREPRGDGGFGYDPVFVPYGDDRTAAQLSPAEKDAVSHRGRALALLLPALRSLATG