nadD Resolved · high auto-curated
H37Rv Rv2421c · MTBC0 - ·
211 aa · 2718173–2718808 (-) ·
RefSeq NP_216937.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | nicotinate-nucleotide adenylyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Nicotinate-nucleotide adenylyltransferase. Pfam: CTP_transf_like (PF01467.33). |
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 |
P9WJJ5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable nicotinate-nucleotide adenylyltransferase |
| EC (curated) |
EC 2.7.7.18
|
| Curated function | Catalyzes the reversible adenylation of nicotinate mononucleotide (NaMN) to nicotinic acid adenine dinucleotide (NaAD). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | nadD |
| eggNOG description | Catalyzes the reversible adenylation of nicotinate mononucleotide (NaMN) to nicotinic acid adenine dinucleotide (NaAD) |
| Orthologous group | COG1057 |
| EC number |
EC 2.7.7.18
|
| KEGG orthology |
K00969
|
| KEGG pathways |
map00760, map01100
|
| KEGG modules |
M00115
|
| Gene Ontology (65) |
GO:0000309, GO:0003674, GO:0003824, GO:0004515, GO:0006082, GO:0006139, GO:0006520, GO:0006531, GO:0006725, GO:0006732, GO:0006733, GO:0006753 +53 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 | 0.506 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
CTP_transf_like | PF01467.33 | 5.1e-29 | 1–166 | Cytidylyltransferase-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gpgP (glucosyl-3-phosphoglycerate phosphatase), high confidence from genomic context alone (score 910 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2420c rsfS hyp |
hypothetical protein | 976 | 969 ctx | neighborhood:882 coexpression:676 |
Rv1901 cinA |
competence damage-inducible protein CinA | 978 | 935 | database:900 textmining:687 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 997 | 934 | database:900 textmining:965 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 948 | 932 | database:900 |
Rv1151c cobB |
NAD-dependent protein deacylase | 947 | 915 | database:900 textmining:408 |
Rv2419c gpgP |
glucosyl-3-phosphoglycerate phosphatase | 910 | 910 ctx | neighborhood:882 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 979 | 909 | database:900 textmining:780 |
Rv0573c pncB2 |
nicotinic acid phosphoribosyltransferase PncB2 | 952 | 909 | database:900 textmining:493 |
Rv1596 nadC |
nicotinate-nucleotide pyrophosphatase | 979 | 908 | database:900 textmining:790 |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa | 908 | 903 | database:900 |
Rv3199c nudC |
NADH pyrophosphatase | 933 | 901 | database:900 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb | 907 | 901 | database:900 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 906 | 901 | database:900 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 904 | 901 | database:900 |
Rv0212c nadR |
transcriptional regulator NadR | 970 | 900 | database:900 textmining:714 |
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): nicotinate-nucleotide adenylyltransferase
- Pfam (hmmscan --cut_ga): CTP_transf_like PF01467.33 (E=5e-29)
- (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_216937.1)
- Domains: Pfam-A via hmmscan --cut_ga — CTP_transf_like (PF01467.33)
- 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
COG1057 - Curated reference: UniProt P9WJJ5 (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 —
64 functional partner(s); context anchor
gpgP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2421c|nadD MGGTFDPIHYGHLVAASEVADLFDLDEVVFVPSGQPWQKGRQVSAAEHRYLMTVIATASNPRFSVSRVDIDRGGPTYTKDTLADLHALHPDSELYFTTGADALASIMSWQGWEELFELARFVGVSRPGYELRNEHITSLLGQLAKDALTLVEIPALAISSTDCRQRAEQSRPLWYLMPDGVVQYVSKCRLYCGACDAGARSTTSLAAGNGL