nadR Resolved · high auto-curated
H37Rv Rv0212c · MTBC0 mtbc0_000226 ·
323 aa · 254021–254992 (-) ·
RefSeq NP_214726.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator NadR |
|---|---|
| MTBC0 PGAP re-annotation | nicotinamide-nucleotide adenylyltransferase |
| Revised (this work) | Nicotinamide-nucleotide adenylyltransferase. Pfam: CTP_transf_like (PF01467.33), AAA_28 (PF13521.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96394
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible transcriptional regulatory protein NadR |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | nadR |
| eggNOG description | AAA domain |
| Orthologous group | COG1056 |
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 | 0.571 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 1 nonsense, 3 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 0.22% of strains (323) · convergent |
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 |
|---|---|---|---|---|
CTP_transf_like | PF01467.33 | 4.5e-04 | 6–100 | Cytidylyltransferase-like |
AAA_28 | PF13521.13 | 2.8e-34 | 154–307 | AAA domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nadE (glutamine-dependent NAD(+) synthetase), high confidence from genomic context alone (score 953 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1151c cobB |
NAD-dependent protein deacylase | 984 | 984 | coexpression:845 database:900 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 990 | 953 ctx | neighborhood:544 database:900 textmining:799 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 941 | 919 | database:900 |
Rv0573c pncB2 |
nicotinic acid phosphoribosyltransferase PncB2 | 948 | 916 | database:900 textmining:416 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 948 | 915 | database:900 textmining:416 |
Rv1901 cinA |
competence damage-inducible protein CinA | 948 | 913 | database:900 textmining:436 |
Rv3307 deoD |
purine nucleoside phosphorylase | 903 | 904 | database:900 |
Rv1596 nadC |
nicotinate-nucleotide pyrophosphatase | 981 | 902 | database:900 textmining:823 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb | 900 | 901 | database:900 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 900 | 901 | database:900 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 970 | 900 | database:900 textmining:714 |
Rv3199c nudC |
NADH pyrophosphatase | 904 | 900 | database:900 |
Rv3393 iunH |
nucleoside hydrolase | 903 | 900 | database:900 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 900 | 900 | database:900 |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa | 900 | 900 | database:900 |
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: transcriptional regulator NadR
- MTBC0 PGAP product: nicotinamide-nucleotide adenylyltransferase
- Pfam (hmmscan --cut_ga): CTP_transf_like PF01467.33 (E=4e-04), AAA_28 PF13521.13 (E=3e-34)
- (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_214726.1)
- Domains: Pfam-A via hmmscan --cut_ga — CTP_transf_like (PF01467.33), AAA_28 (PF13521.13)
- 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
COG1056 - Curated reference: UniProt P96394 (TrEMBL, unreviewed; Predicted)
- 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 —
87 functional partner(s); context anchor
nadE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000226|Rv0212c|nadR MTHGMVLGKFMPPHAGHVYLCEFARRWVDELTIVVGSTAAEPIPGAQRVAWMRELFPFDRVVHLANENPQRPWEHPDFWDIWKASLQGVLATRPDFVFGAEPYNADFAQVLGARFVAVDHGRTVVPVTATDIRADPLGHWQHIPRCVRPAFVKRVSIIGPESTGKTTLAQAVAEKLRTKWVPERAKMLRELNGGSLIGLEWAEIVRGQIASEEALARDADRVLICDTDPLATTVWAEFLAGGCPQELRDLARRPYDLTLLTTPDVPWDADDGRCVPGARGTFFARCEQALRAAGRSFVVITGGWEERLSVSLRAVEELVRARR