nadE Resolved · high auto-curated
H37Rv Rv2438c · MTBC0 mtbc0_002596 ·
668 aa · 2759040–2761046 (-) ·
RefSeq NP_216954.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glutamine-dependent NAD(+) synthetase |
|---|---|
| MTBC0 PGAP re-annotation | NAD(+) synthase |
| Revised (this work) | NAD(+) synthase. Pfam: CN_hydrolase (PF00795.28), NAD_synthase (PF02540.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJJ3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Glutamine-dependent NAD(+) synthetase |
| EC (curated) |
EC 6.3.5.1
|
| Curated function | Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD. Uses L-glutamine as a nitrogen source. In vitro, can also use ammonia with comparable specific activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | nadE |
| eggNOG description | Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD. Uses L-glutamine as a nitrogen source |
| Orthologous group | COG0171 |
| EC number |
EC 6.3.5.1
|
| KEGG orthology |
K01950
|
| KEGG pathways |
map00760, map01100
|
| KEGG modules |
M00115
|
| Gene Ontology (68) |
GO:0003674, GO:0003824, GO:0003952, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006139 +56 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 | 0.338 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 5 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 |
|---|---|---|---|---|
CN_hydrolase | PF00795.28 | 1.1e-18 | 2–270 | Carbon-nitrogen hydrolase |
NAD_synthase | PF02540.24 | 1.2e-22 | 336–509 | NAD synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nadR (transcriptional regulator NadR), high confidence from genomic context alone (score 953 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0212c nadR |
transcriptional regulator NadR | 990 | 953 ctx | neighborhood:544 database:900 textmining:799 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 997 | 934 | database:900 textmining:965 |
Rv1151c cobB |
NAD-dependent protein deacylase | 963 | 926 | database:900 textmining:529 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 959 | 924 | database:900 textmining:498 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 932 | 924 | database:919 |
Rv3199c nudC |
NADH pyrophosphatase | 939 | 907 | database:900 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 929 | 901 | database:900 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb | 909 | 901 | database:900 |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa | 909 | 900 | database:900 |
Rv3396c guaA |
GMP synthase | 932 | 640 ctx | neighborhood:544 textmining:820 |
Rv3339c icd1 |
isocitrate dehydrogenase | 646 | 632 | database:549 |
Rv3728 |
membrane protein | 660 | 629 ctx | neighborhood:544 |
Rv3239c |
transmembrane transport protein | 658 | 627 ctx | neighborhood:544 |
Rv2535c pepQ |
cytoplasmic peptidase PepQ | 620 | 620 | database:497 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 635 | 619 |
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: glutamine-dependent NAD(+) synthetase
- MTBC0 PGAP product: NAD(+) synthase
- Pfam (hmmscan --cut_ga): CN_hydrolase PF00795.28 (E=1e-18), NAD_synthase PF02540.24 (E=1e-22)
- (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_216954.2)
- Domains: Pfam-A via hmmscan --cut_ga — CN_hydrolase (PF00795.28), NAD_synthase (PF02540.24)
- 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
COG0171 - Curated reference: UniProt P9WJJ3 (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 —
183 functional partner(s); context anchor
nadR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002596|Rv2438c|nadE MRVAACTHHTTIGDPAANAASVLDMARACHDDGAALAVFPELTLSGYSIEDVLLQDSLLDAVEDALLDLVTESADLLPVLVVGAPLRHRHRIYNTAVVIHRGAVLGVVPKSYLPTYREFYERRQMAPGDGERGTIRIGGADVAFGTDLLFAASDLPGFVLHVEICEDMFVPMPPSAEAALAGATVLANLSGSPITIGRAEDRRLLARSASARCLAAYVYAAAGEGESTTDLAWDGQTMIWENGALLAESERFPKGVRRSVADVDTELLRSERLRMGTFDDNRRHHRELTESFRRIDFALDPPAGDIGLLREVERFPFVPADPQRLQQDCYEAYNIQVSGLEQRLRALDYPKVVIGVSGGLDSTHALIVATHAMDREGRPRSDILAFALPGFATGEHTKNNAIKLARALGVTFSEIDIGDTARLMLHTIGHPYSVGEKVYDVTFENVQAGLRTDYLFRIANQRGGIVLGTGDLSELALGWSTYGVGDQMSHYNVNAGVPKTLIQHLIRWVISAGEFGEKVGEVLQSVLDTEITPELIPTGEEELQSSEAKVGPFALQDFSLFQVLRYGFRPSKIAFLAWHAWNDAERGNWPPGFPKSERPSYSLAEIRHWLQIFVQRFYSFSQFKRSALPNGPKVSHGGALSPRGDWRAPSDMSARIWLDQIDREVPKG