nadC Resolved · high auto-curated
H37Rv Rv1596 · MTBC0 mtbc0_001702 ·
285 aa · 1809352–1810209 (+) ·
RefSeq NP_216112.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | nicotinate-nucleotide pyrophosphatase |
|---|---|
| MTBC0 PGAP re-annotation | carboxylating nicotinate-nucleotide diphosphorylase |
| Revised (this work) | Carboxylating nicotinate-nucleotide diphosphorylase. Pfam: QRPTase_N (PF02749.23), QRPTase_C (PF01729.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJJ7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nicotinate-nucleotide pyrophosphorylase [carboxylating] |
| EC (curated) |
EC 2.4.2.19
|
| Curated function | Involved in the catabolism of quinolinic acid (QA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | nadC |
| eggNOG description | Belongs to the NadC ModD family |
| Orthologous group | COG0157 |
| EC number |
EC 2.4.2.19
|
| KEGG orthology |
K00767
|
| KEGG pathways |
map00760, map01100
|
| KEGG modules |
M00115
|
| Gene Ontology (82) |
GO:0003674, GO:0003824, GO:0004514, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006139, GO:0006725 +70 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 | 0.383 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
QRPTase_N | PF02749.23 | 8.8e-18 | 28–115 | Quinolinate phosphoribosyl transferase, N-terminal domain |
QRPTase_C | PF01729.26 | 6.0e-64 | 117–284 | Quinolinate phosphoribosyl transferase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nadB (L-aspartate oxidase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1595 nadB |
L-aspartate oxidase | 999 | 1000 ctx | neighborhood:881 fusion:869 cooccurence:767 coexpression:947 textmining:965 |
Rv1594 nadA |
quinolinate synthetase A | 999 | 1000 ctx | neighborhood:881 cooccurence:773 coexpression:881 database:900 textmining:965 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 993 | 931 | database:900 textmining:915 |
Rv0573c pncB2 |
nicotinic acid phosphoribosyltransferase PncB2 | 967 | 931 | database:900 textmining:543 |
Rv1901 cinA |
competence damage-inducible protein CinA | 971 | 912 | database:900 textmining:694 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 979 | 908 | database:900 textmining:790 |
Rv3199c nudC |
NADH pyrophosphatase | 943 | 904 | database:900 textmining:433 |
Rv0212c nadR |
transcriptional regulator NadR | 981 | 902 | database:900 textmining:823 |
Rv1593c hyp |
hypothetical protein | 845 | 838 ctx | neighborhood:788 |
Rv1597 hyp |
hypothetical protein | 675 | 672 ctx | neighborhood:665 |
Rv3025c iscS |
cysteine desulfurase | 625 | 528 | coexpression:426 |
Rv1552 frdA |
fumarate reductase flavoprotein subunit | 522 | 487 | |
Rv1589 bioB |
biotin synthetase | 481 | 448 | |
Rv1416 ribH |
6,7-dimethyl-8-ribityllumazine synthase | 571 | 441 | coexpression:408 |
Rv1570 bioD |
ATP-dependent dethiobiotin synthetase BioD | 547 | 426 |
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: nicotinate-nucleotide pyrophosphatase
- MTBC0 PGAP product: carboxylating nicotinate-nucleotide diphosphorylase
- Pfam (hmmscan --cut_ga): QRPTase_N PF02749.23 (E=9e-18), QRPTase_C PF01729.26 (E=6e-64)
- (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_216112.1)
- Domains: Pfam-A via hmmscan --cut_ga — QRPTase_N (PF02749.23), QRPTase_C (PF01729.26)
- 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
COG0157 - Curated reference: UniProt P9WJJ7 (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 —
30 functional partner(s); context anchor
nadB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001702|Rv1596|nadC MGLSDWELAAARAAIARGLDEDLRYGPDVTTLATVPASATTTASLVTREAGVVAGLDVALLTLDEVLGTNGYRVLDRVEDGARVPPGEALMTLEAQTRGLLTAERTMLNLVGHLSGIATATAAWVDAVRGTKAKIRDTRKTLPGLRALQKYAVRTGGGVNHRLGLGDAALIKDNHVAAAGSVVDALRAVRNAAPDLPCEVEVDSLEQLDAVLPEKPELILLDNFAVWQTQTAVQRRDSRAPTVMLESSGGLSLQTAATYAETGVDYLAVGALTHSVRVLDIGLDM