pncB2 Resolved · high auto-curated
H37Rv Rv0573c · MTBC0 mtbc0_000603 ·
463 aa · 669402–670793 (-) ·
RefSeq NP_215087.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | nicotinic acid phosphoribosyltransferase PncB2 |
|---|---|
| MTBC0 PGAP re-annotation | nicotinate phosphoribosyltransferase |
| Revised (this work) | Nicotinate phosphoribosyltransferase. Pfam: NAPRTase_N (PF17767.8), 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 |
P9WJI7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nicotinate phosphoribosyltransferase pncB2 |
| EC (curated) |
EC 6.3.4.21
|
| Curated function | Involved 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. PncB2 appears to be responsible for the increased salvage synthesis of NAD during infection of host tissues. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| eggNOG description | Catalyzes the synthesis of beta-nicotinate D- ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate at the expense of ATP |
| Orthologous group | COG1488 |
| EC number |
EC 6.3.4.21
|
| KEGG orthology |
K00763
|
| KEGG pathways |
map00760, map01100
|
| Gene Ontology (79) |
GO:0001666, GO:0003674, GO:0003824, GO:0004516, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006725, GO:0006732, GO:0006733, GO:0006753 +67 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 | 0.513 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 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 |
|---|---|---|---|---|
NAPRTase_N | PF17767.8 | 1.8e-35 | 10–132 | Nicotinate phosphoribosyltransferase (NAPRTase) N-terminal domain |
NAPRTase | PF04095.23 | 7.9e-12 | 154–329 | 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 977 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 987 | 977 ctx | fusion:410 cooccurence:572 database:900 textmining:475 |
Rv0574c hyp |
hypothetical protein | 975 | 975 ctx | neighborhood:801 coexpression:860 |
Rv1596 nadC |
nicotinate-nucleotide pyrophosphatase | 967 | 931 | database:900 textmining:543 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 926 | 920 | database:900 |
Rv1901 cinA |
competence damage-inducible protein CinA | 960 | 919 | database:900 textmining:532 |
Rv0212c nadR |
transcriptional regulator NadR | 948 | 916 | database:900 textmining:416 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 952 | 909 | database:900 textmining:493 |
Rv3199c nudC |
NADH pyrophosphatase | 939 | 905 | database:900 |
Rv3307 deoD |
purine nucleoside phosphorylase | 909 | 904 | database:900 |
Rv1997 ctpF |
cation transporter ATPase F | 758 | 759 | coexpression:751 |
Rv0575c |
oxidoreductase | 577 | 552 ctx | neighborhood:470 |
Rv2003c hyp |
hypothetical protein | 553 | 549 | coexpression:474 |
Rv2004c hyp |
hypothetical protein | 492 | 492 | |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 717 | 489 | coexpression:415 textmining:469 |
Rv2624c |
universal stress protein | 403 | 401 |
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 PncB2
- MTBC0 PGAP product: nicotinate phosphoribosyltransferase
- Pfam (hmmscan --cut_ga): NAPRTase_N PF17767.8 (E=2e-35), NAPRTase PF04095.23 (E=8e-12)
- (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_215087.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAPRTase_N (PF17767.8), 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 P9WJI7 (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 —
19 functional partner(s); context anchor
pncA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000603|Rv0573c|pncB2 MAIRQHVGALFTDLYEVTMAQAYWAERMSGTAVFEIFFRKLPPGRSYIMAAGLADVVEFLEAFRFDEQDLRYLRGLGQFSDEFLRWLAGVRFTGDVWAAPEGTVIFPNEPAVQLIAPIIEAQLVETFVLNQIHLQSVLASKAARVVAAARGRPVVDFGARRAHGTDAACKVARTSYLAGAAGTSNLLAARQYGIPTFGTMAHSFVQAFDSEVAAFEAFARLYPATMLLVDTYDTLRGVDHVIELAKRLGNRFDVRAVRLDSGDLDELSKATRARLDTAGLEQVEIFASSGLDENRIAALLAARCPIDGFGVGTQLVVAQDAPALDMAYKLVAYDGSGRTKFSSGKVIYPGRKQVFRKLEHGVFCGDTLGEHGENLPGDPLLVPIMTNGRRIRQHAPTLDGARDWARQQIDALPPELRSLEDTGYSYPVAVSDRIVGELARLRHADTAEAHPGSNVVGAKAKRP