nadA Resolved · high auto-curated
H37Rv Rv1594 · MTBC0 - ·
349 aa · 1794756–1795805 (+) ·
RefSeq NP_216110.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | quinolinate synthetase A |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Quinolinate synthetase A. Pfam: NadA (PF02445.22). |
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 |
P9WJK1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Quinolinate synthase |
| EC (curated) |
EC 2.5.1.72
|
| Curated function | Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | nadA |
| eggNOG description | Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate |
| Orthologous group | COG0379 |
| EC number |
EC 2.5.1.72
|
| KEGG orthology |
K03517
|
| KEGG pathways |
map00760, map01100
|
| KEGG modules |
M00115
|
| Gene Ontology (83) |
GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006139, GO:0006520 +71 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 | 1.016 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
NadA | PF02445.22 | 8.8e-109 | 37–341 | Quinolinate synthetase A protein |
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 cooccurence:769 coexpression:966 experimental:446 database:900 textmining:944 |
Rv1596 nadC |
nicotinate-nucleotide pyrophosphatase | 999 | 1000 ctx | neighborhood:881 cooccurence:773 coexpression:881 database:900 textmining:965 |
Rv1593c hyp |
hypothetical protein | 889 | 883 ctx | neighborhood:788 cooccurence:443 |
Rv2335 cysE |
serine acetyltransferase | 732 | 732 | coexpression:711 |
Rv1389 gmk |
guanylate kinase | 688 | 687 | coexpression:669 |
Rv2448c valS |
valine--tRNA ligase | 667 | 667 ctx | fusion:652 |
Rv1597 hyp |
hypothetical protein | 657 | 644 ctx | neighborhood:641 |
Rv3859c gltB |
glutamate synthase large subunit | 546 | 546 ctx | neighborhood:544 |
Rv3025c iscS |
cysteine desulfurase | 576 | 506 | coexpression:418 |
Rv1589 bioB |
biotin synthetase | 537 | 447 | coexpression:415 |
Rv1592c hyp |
hypothetical protein | 408 | 408 ctx | neighborhood:401 |
Rv1570 bioD |
ATP-dependent dethiobiotin synthetase BioD | 478 | 400 | |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 564 | 291 | textmining:411 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 859 | 257 | textmining:818 |
Rv1631 coaE |
dephospho-CoA kinase CoaE | 569 | 169 | textmining:503 |
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): quinolinate synthetase A
- Pfam (hmmscan --cut_ga): NadA PF02445.22 (E=9e-109)
- (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_216110.1)
- Domains: Pfam-A via hmmscan --cut_ga — NadA (PF02445.22)
- 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
COG0379 - Curated reference: UniProt P9WJK1 (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 —
41 functional partner(s); context anchor
nadB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1594|nadA MTVLNRTDTLVDELTADITNTPLGYGGVDGDERWAAEIRRLAHLRGATVLAHNYQLPAIQDVADHVGDSLALSRVAAEAPEDTIVFCGVHFMAETAKILSPHKTVLIPDQRAGCSLADSITPDELRAWKDEHPGAVVVSYVNTTAAVKALTDICCTSSNAVDVVASIDPDREVLFCPDQFLGAHVRRVTGRKNLHVWAGECHVHAGINGDELADQARAHPDAELFVHPECGCATSALYLAGEGAFPAERVKILSTGGMLEAAHTTRARQVLVATEVGMLHQLRRAAPEVDFRAVNDRASCKYMKMITPAALLRCLVEGADEVHVDPGIAASGRRSVQRMIEIGHPGGGE