nadB Resolved · high auto-curated

H37Rv Rv1595 · MTBC0 mtbc0_001701 · 527 aa · 1807769–1809352 (+) · RefSeq NP_216111.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)L-aspartate oxidase
MTBC0 PGAP re-annotationL-aspartate oxidase
Revised (this work)L-aspartate oxidase. Pfam: FAD_binding_2 (PF00890.31), Succ_DH_flav_C (PF02910.26).

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

Curated reference (UniProt)

UniProt P9WJJ9 SwissProt · reviewed · Evidence at protein level
UniProt nameL-aspartate oxidase
EC (curated) EC 1.4.3.16
Curated functionCatalyzes the oxidation of L-aspartate to iminoaspartate, the first step in the de novo biosynthesis of NAD(+).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namenadB
eggNOG descriptionCatalyzes the oxidation of L-aspartate to iminoaspartate
Orthologous groupCOG0029
EC number EC 1.4.3.16
KEGG orthology K00278
KEGG pathways map00250, map00760, map01100
KEGG modules M00115
Gene Ontology (2) GO:0008150, GO:0040007

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 0.744 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 10 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)

PfamAccessioni-EvalueResiduesDescription
FAD_binding_2PF00890.31 3.1e-8811–381 FAD binding domain
Succ_DH_flav_CPF02910.26 1.6e-06426–498 Fumarate reductase flavoprotein C-term

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

Closest characterised functional partner: nadA (quinolinate synthetase A), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1594 nadA quinolinate synthetase A 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 fusion:869 cooccurence:767 coexpression:947 textmining:965
Rv1538c ansA L-aparaginase 918 905 database:900
Rv1380 pyrB aspartate carbamoyltransferase 909 902 database:900
Rv0357c purA adenylosuccinate synthetase 913 901 database:900
Rv1658 argG argininosuccinate synthase 913 901 database:900
Rv2201 asnB asparagine synthetase 903 900 database:900
Rv3601c panD aspartate 1-decarboxylase 845 830 database:800
Rv1593c hyp hypothetical protein 832 825 ctx neighborhood:788
Rv3709c ask aspartokinase 824 815 database:800
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 826 812 database:800
Rv0066c icd2 isocitrate dehydrogenase 809 809 database:800
Rv1240 mdh malate dehydrogenase 835 808 database:800
Rv0211 pckA phosphoenolpyruvate carboxykinase 817 807 database:800
Rv3432c gadB glutamate decarboxylase GadB 806 806 database:800

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: L-aspartate oxidase
  • MTBC0 PGAP product: L-aspartate oxidase
  • Pfam (hmmscan --cut_ga): FAD_binding_2 PF00890.31 (E=3e-88), Succ_DH_flav_C PF02910.26 (E=2e-06)
  • (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_216111.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_2 (PF00890.31), Succ_DH_flav_C (PF02910.26)
  • 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 COG0029
  • Curated reference: UniProt P9WJJ9 (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 — 42 functional partner(s); context anchor nadA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001701|Rv1595|nadB
MAGPAWRDAADVVVIGTGVAGLAAALAADRAGRSVVVLSKAAQTHVTATHYAQGGIAVVLPDNDDSVDAHVADTLAAGAGLCDPDAVYSIVADGYRAVTDLVGAGARLDESVPGRWALTREGGHSRRRIVHAGGDATGAEVQRALQDAAGMLDIRTGHVALRVLHDGTAVTGLLVVRPDGCGIISAPSVILATGGLGHLYSATTNPAGSTGDGIALGLWAGVAVSDLEFIQFHPTMLFAGRAGGRRPLITEAIRGEGAILVDRQGNSITAGVHPMGDLAPRDVVAAAIDARLKATGDPCVYLDARGIEGFASRFPTVTASCRAAGIDPVRQPIPVVPGAHYSCGGIVTDVYGQTELLGLYAAGEVARTGLHGANRLASNSLLEGLVVGGRAGKAAAAHAAAAGRSRATSSATWPEPISYTALDRGDLQRAMSRDASMYRAAAGLHRLCDSLSGAQVRDVACRRDFEDVALTLVAQSVTAAALARTESRGCHHRAEYPCTVPEQARSIVVRGADDANAVCVQALVAVC