nudC Resolved · high auto-curated
H37Rv Rv3199c · MTBC0 mtbc0_003403 ·
313 aa · 3593744–3594685 (-) ·
RefSeq NP_217715.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NADH pyrophosphatase |
|---|---|
| MTBC0 PGAP re-annotation | NAD(+) diphosphatase |
| Revised (this work) | NAD(+) diphosphatase. Pfam: NUDIX-like (PF09296.18), Zn_ribbon_NUD (PF09297.17), NUDIX (PF00293.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIX5
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | NAD-capped RNA hydrolase NudC |
| EC (curated) |
EC 3.6.1.-, EC 3.6.1.22
|
| Curated function | mRNA decapping enzyme that specifically removes the nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs by hydrolyzing the diphosphate linkage to produce nicotinamide mononucleotide (NMN) and 5' monophosphate mRNA. The NAD-cap is present at the 5'-end of some mRNAs and stabilizes RNA against 5'-processing. Has preference for mRNAs with a 5'-end purine. Catalyzes the hydrolysis of a broad range of dinucleotide pyrophosphates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | nudC |
| eggNOG description | NADH pyrophosphatase |
| Orthologous group | COG2816 |
| EC number |
EC 3.6.1.22
|
| KEGG orthology |
K03426
|
| KEGG pathways |
map00760, map01100, map04146
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 1.735 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
NUDIX-like | PF09296.18 | 4.6e-06 | 50–134 | NADH pyrophosphatase-like rudimentary NUDIX domain |
Zn_ribbon_NUD | PF09297.17 | 1.5e-09 | 136–167 | NADH pyrophosphatase zinc ribbon domain |
NUDIX | PF00293.35 | 5.7e-21 | 172–283 | NUDIX domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: adnA (ATP-dependent DNA helicase), high confidence from genomic context alone (score 828 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1151c cobB |
NAD-dependent protein deacylase | 941 | 912 | database:900 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 939 | 907 | database:900 |
Rv1901 cinA |
competence damage-inducible protein CinA | 955 | 906 | database:900 textmining:547 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 961 | 905 | database:900 textmining:609 |
Rv0573c pncB2 |
nicotinic acid phosphoribosyltransferase PncB2 | 939 | 905 | database:900 |
Rv1596 nadC |
nicotinate-nucleotide pyrophosphatase | 943 | 904 | database:900 textmining:433 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 933 | 901 | database:900 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 905 | 901 | database:900 |
Rv0156 pntAb |
NAD(P) transhydrogenase subunit alpha PntAb | 903 | 901 | database:900 |
Rv0157 pntB |
NAD(P) transhydrogenase subunit beta PntB | 900 | 901 | database:900 |
Rv0155 pntAa |
NAD(P) transhydrogenase subunit alpha PntAa | 900 | 901 | database:900 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 910 | 900 | database:900 |
Rv0212c nadR |
transcriptional regulator NadR | 904 | 900 | database:900 |
Rv3202c adnA |
ATP-dependent DNA helicase | 828 | 828 ctx | neighborhood:747 |
Rv3200c |
transmembrane cation transporter | 810 | 810 ctx | neighborhood:804 |
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: NADH pyrophosphatase
- MTBC0 PGAP product: NAD(+) diphosphatase
- Pfam (hmmscan --cut_ga): NUDIX-like PF09296.18 (E=5e-06), Zn_ribbon_NUD PF09297.17 (E=1e-09), NUDIX PF00293.35 (E=6e-21)
- (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_217715.1)
- Domains: Pfam-A via hmmscan --cut_ga — NUDIX-like (PF09296.18), Zn_ribbon_NUD (PF09297.17), NUDIX (PF00293.35)
- 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
COG2816 - Curated reference: UniProt P9WIX5 (SwissProt, reviewed; Inferred from homology)
- 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 —
29 functional partner(s); context anchor
adnA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003403|Rv3199c|nudC MTNVSGVDFQLRSVPLLSRVGADRADRLRTDMEAAAAGWPGAALLRVDSRNRVLVANGRVLLGAAIELADKPPPEAVFLGRVEGGRHVWAVRAALQPIADPDIPAEAVDLRGLGRIMDDTSSQLVSSASALLNWHDNARFSALDGAPTKPARAGWSRVNPITGHEEFPRIDPAVICLVHDGADRAVLARQAAWPERMFSLLAGFVEAGESFEVCVAREIREEIGLTVRDVRYLGSQPWPFPRSLMVGFHALGDPDEEFSFSDGEIAEAAWFTRDEVRAALAAGDWSSASESKLLLPGSISIARVIIESWAACE