ppnK Resolved · high auto-curated
H37Rv Rv1695 · MTBC0 mtbc0_001803 ·
307 aa · 1930761–1931684 (+) ·
RefSeq NP_216211.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | inorganic polyphosphate/ATP-NAD kinase |
|---|---|
| MTBC0 PGAP re-annotation | NAD kinase |
| Revised (this work) | NAD kinase. Pfam: NAD_kinase (PF01513.27), NAD_kinase_C (PF20143.5). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHV7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | NAD kinase |
| EC (curated) |
EC 2.7.1.23
|
| Curated function | Involved in the regulation of the intracellular balance of NAD and NADP, and is a key enzyme in the biosynthesis of NADP. Catalyzes specifically the phosphorylation on 2'-hydroxyl of the adenosine moiety of NAD to yield NADP. It can use ATP and other nucleoside triphosphates as well as inorganic polyphosphate (poly(P)) as a source of phosphorus. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | nadK |
| eggNOG description | Involved in the regulation of the intracellular balance of NAD and NADP, and is a key enzyme in the biosynthesis of NADP. Catalyzes specifically the phosphorylation on 2'-hydroxyl of the adenosine moiety of NAD to yield NADP |
| Orthologous group | COG0061 |
| EC number |
EC 2.7.1.23
|
| KEGG orthology |
K00858
|
| KEGG pathways |
map00760, map01100
|
| Gene Ontology (77) |
GO:0000166, GO:0003674, GO:0003824, GO:0003951, GO:0005488, GO:0005524, GO:0006082, GO:0006139, GO:0006725, GO:0006732, GO:0006733, GO:0006739 +65 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 | 0.142 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 2 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 |
|---|---|---|---|---|
NAD_kinase | PF01513.27 | 4.4e-31 | 7–133 | ATP-NAD kinase N-terminal domain |
NAD_kinase_C | PF20143.5 | 1.0e-38 | 158–283 | ATP-NAD kinase C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tlyA (16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA), high confidence from genomic context alone (score 938 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1694 tlyA |
16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA | 986 | 938 ctx | neighborhood:882 coexpression:494 textmining:790 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 948 | 932 | database:900 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 959 | 924 | database:900 textmining:498 |
Rv0212c nadR |
transcriptional regulator NadR | 941 | 919 | database:900 |
Rv1151c cobB |
NAD-dependent protein deacylase | 923 | 906 | database:900 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 910 | 903 | database:900 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb | 916 | 901 | database:900 |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa | 913 | 901 | database:900 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 907 | 901 | database:900 |
Rv3199c nudC |
NADH pyrophosphatase | 905 | 901 | database:900 |
Rv1691 hyp |
hypothetical protein | 986 | 900 ctx | neighborhood:882 textmining:870 |
Rv1693 hyp |
hypothetical protein | 984 | 884 ctx | neighborhood:882 textmining:870 |
Rv1692 |
phosphatase | 984 | 882 ctx | neighborhood:882 textmining:870 |
Rv1696 recN |
DNA repair protein RecN | 978 | 882 ctx | neighborhood:867 textmining:821 |
Rv1697 steA hyp |
hypothetical protein | 769 | 769 ctx | neighborhood:766 |
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: inorganic polyphosphate/ATP-NAD kinase
- MTBC0 PGAP product: NAD kinase
- Pfam (hmmscan --cut_ga): NAD_kinase PF01513.27 (E=4e-31), NAD_kinase_C PF20143.5 (E=1e-38)
- (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_216211.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_kinase (PF01513.27), NAD_kinase_C (PF20143.5)
- 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
COG0061 - Curated reference: UniProt P9WHV7 (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 —
65 functional partner(s); context anchor
tlyA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001803|Rv1695|ppnK MTAHRSVLLVVHTGRDEATETARRVEKVLGDNKIALRVLSAEAVDRGSLHLAPDDMRAMGVEIEVVDADQHAADGCELVLVLGGDGTFLRAAELARNASIPVLGVNLGRIGFLAEAEAEAIDAVLEHVVAQDYRVEDRLTLDVVVRQGGRIVNRGWALNEVSLEKGPRLGVLGVVVEIDGRPVSAFGCDGVLVSTPTGSTAYAFSAGGPVLWPDLEAILVVPNNAHALFGRPMVTSPEATIAIEIEADGHDALVFCDGRREMLIPAGSRLEVTRCVTSVKWARLDSAPFTDRLVRKFRLPVTGWRGK