pncB1 Resolved · high auto-curated

H37Rv Rv1330c · MTBC0 mtbc0_001427 · 448 aa · 1509915–1511261 (-) · RefSeq NP_215846.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nicotinic acid phosphoribosyltransferase PncB1
MTBC0 PGAP re-annotationnicotinate phosphoribosyltransferase
Revised (this work)Nicotinate phosphoribosyltransferase. Pfam: NAPRTase_N (PF17767.8), QRPTase_C (PF01729.26), NAPRTase (PF04095.23).

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

Curated reference (UniProt)

UniProt P9WJI9 SwissProt · reviewed · Evidence at protein level
UniProt nameNicotinate phosphoribosyltransferase pncB1
EC (curated) EC 6.3.4.21
Curated functionInvolved in the Preiss-Handler pathway, which is a recycling route that permits the salvage of free nicotinamide (NM) and nicotinic acid (Na) involved in the NAD biosynthesis. Catalyzes the synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP. It is not able to use nicotinamide. PncB1 contributes to basal NAD level.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namepncB
eggNOG descriptionCatalyzes the synthesis of beta-nicotinate D- ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP
Orthologous groupCOG1488
EC number EC 6.3.4.21
KEGG orthology K00763
KEGG pathways map00760, map01100
Gene Ontology (64) GO:0003674, GO:0003824, GO:0004516, GO:0005575, GO:0005618, GO:0005623, GO:0006139, GO:0006725, GO:0006732, GO:0006733, GO:0006753, GO:0006793 +52 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) pseudogene candidate

pN/pS 1.524 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 8 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 5.96% of strains (8658) · 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
NAPRTase_NPF17767.8 2.0e-2722–144 Nicotinate phosphoribosyltransferase (NAPRTase) N-terminal domain
QRPTase_CPF01729.26 6.0e-05149–325 Quinolinate phosphoribosyl transferase, C-terminal domain
NAPRTasePF04095.23 2.5e-05166–362 Nicotinate phosphoribosyltransferase (NAPRTase) family

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

Closest characterised functional partner: pncA (pyrazinamidase/nicotinamidase PncA), high confidence from genomic context alone (score 988 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2043c pncA pyrazinamidase/nicotinamidase PncA 994 988 ctx fusion:567 cooccurence:654 database:900 textmining:585
Rv1596 nadC nicotinate-nucleotide pyrophosphatase 993 931 database:900 textmining:915
Rv0573c pncB2 nicotinic acid phosphoribosyltransferase PncB2 926 920 database:900
Rv1901 cinA competence damage-inducible protein CinA 977 919 database:900 textmining:729
Rv0212c nadR transcriptional regulator NadR 948 915 database:900 textmining:416
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 979 909 database:900 textmining:780
Rv3199c nudC NADH pyrophosphatase 961 905 database:900 textmining:609
Rv3307 deoD purine nucleoside phosphorylase 908 904 database:900
Rv1329c dinG ATP-dependent helicase DinG 830 830 ctx neighborhood:817
Rv1331 clpS ATP-dependent Clp protease adapter protein ClpS 789 781 ctx neighborhood:780
Rv1332 transcriptional regulator 782 781 ctx neighborhood:780
Rv1333 hydrolase 764 764 ctx neighborhood:763
Rv1334 mec [CysO 755 755 ctx neighborhood:717
Rv1335 cysO sulfur carrier protein CysO 751 752 ctx neighborhood:750
Rv1336 cysM O-phosphoserine sulfhydrylase 749 749 ctx neighborhood:747

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: nicotinic acid phosphoribosyltransferase PncB1
  • MTBC0 PGAP product: nicotinate phosphoribosyltransferase
  • Pfam (hmmscan --cut_ga): NAPRTase_N PF17767.8 (E=2e-27), QRPTase_C PF01729.26 (E=6e-05), NAPRTase PF04095.23 (E=3e-05)
  • (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_215846.2)
  • Domains: Pfam-A via hmmscan --cut_ga — NAPRTase_N (PF17767.8), QRPTase_C (PF01729.26), NAPRTase (PF04095.23)
  • 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 COG1488
  • Curated reference: UniProt P9WJI9 (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 — 31 functional partner(s); context anchor pncA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001427|Rv1330c|pncB1
MGPPPAARRREGEPDNQDPAGLLTDKYELTMLAAALRDGSANRPTTFEVFARRLPTGRRYGVVAGTGRLLEALPQFRFDADACELLAQFLDPATVRYLREFRFRGDIDGYAEGELYFPGSPVLSVRGSFAECVLLETLVLSIFNHDTAIASAAARMVSAAGGRPLIEMGSRRTHERAAVAAARAAYIAGFAASSNLAAQRRYGVPAHGTAAHAFTMLHAQHGGPTELAERAAFRAQVEALGPGTTLLVDTYDVTTGVANAVAAAGAELGAIRIDSGELGVLARQAREQLDRLGATRTRIVVSGDLDEFSIAALRGEPVDSYGVGTSLVTGSGAPTANMVYKLVEVDGVPVQKRSSYKESPGGRKEALRRSRATGTITEELVHPAGRPPVIVEPHRVLTLPLVRAGQPVADTSLAAARQLVASGLRSLPADGLKLAPGEPAIPTRTIPA