Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | vitamin B12-dependent ribonucleoside-diphosphate reductase |
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| MTBC0 PGAP re-annotation | adenosylcobalamin-dependent ribonucleoside-diphosphate reductase |
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| Revised (this work) | Adenosylcobalamin-dependent ribonucleoside-diphosphate reductase. Pfam: ATP-cone (PF03477.22), Ribonuc_red_lgN (PF00317.27), Ribonuc_red_lgC (PF02867.21). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WH77
SwissProt · reviewed
· Evidence at protein level
|
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| UniProt name | Vitamin B12-dependent ribonucleoside-diphosphate reductase |
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| EC (curated) |
EC 1.17.4.1
|
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| Curated function | Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides (By similarity). |
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Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
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| Preferred name | nrdJ |
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| eggNOG description | Catalyzes the reduction of ribonucleotides to deoxyribonucleotides. May function to provide a pool of deoxyribonucleotide precursors for DNA repair during oxygen limitation and or for immediate growth after restoration of oxygen |
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| Orthologous group | COG0209 |
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| EC number |
EC 1.17.4.1
|
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| KEGG orthology |
K00525
|
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| KEGG pathways |
map00230, map00240, map01100
|
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| KEGG modules |
M00053
|
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| Gene Ontology (13) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, GO:0044424, GO:0044444, GO:0044464 +1 more
|
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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 |
1.101 · relaxed/neutral
|
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| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 12 missense, 0 nonsense, 6 frameshift
|
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| Disruption |
6 distinct premature-stop/frameshift site(s); most common in
9.95% of strains
(14444) · convergent
|
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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 |
|---|
ATP-cone | PF03477.22 |
1.5e-17 | 8–92 |
ATP cone domain |
Ribonuc_red_lgN | PF00317.27 |
3.3e-18 | 108–188 |
Ribonucleotide reductase, all-alpha domain |
Ribonuc_red_lgC | PF02867.21 |
1.0e-127 | 192–655 |
Ribonucleotide reductase, barrel domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3048c nrdF2 |
ribonucleoside-diphosphate reductase subunit beta NrdF2 |
992 |
986 |
coexpression:649 experimental:600 database:900 textmining:492 |
Rv1981c nrdF1 |
ribonucleoside-diphosphate reductase subunit beta NrdF1 |
989 |
986 |
coexpression:647 experimental:600 database:900 |
Rv0233 nrdB |
ribonucleoside-diphosphate reductase subunit beta NrdB |
987 |
985 |
coexpression:648 experimental:600 database:900 |
Rv0038 hyp |
hypothetical protein |
969 |
965 |
coexpression:548 experimental:789 database:662 |
Rv3247c tmk |
thymidylate kinase |
932 |
923 |
database:900 |
Rv1712 cmk |
cytidylate kinase |
922 |
913 |
database:900 |
Rv3051c nrdE |
ribonucleoside-diphosphate reductase subunit alpha |
915 |
907 |
database:900 |
Rv0733 adk |
adenylate kinase |
914 |
902 |
database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase |
912 |
901 |
database:900 |
Rv1389 gmk |
guanylate kinase |
910 |
901 |
database:900 |
Rv1617 pykA |
pyruvate kinase |
907 |
901 |
database:900 |
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA |
904 |
900 |
database:900 |
Rv3053c nrdH |
glutaredoxin electron transport protein NrdH |
878 |
864 |
database:614 |
Rv0508 hyp |
hypothetical protein |
863 |
851 |
database:614 |
Rv3198A |
glutaredoxin protein |
859 |
851 |
database:614 |
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: vitamin B12-dependent ribonucleoside-diphosphate reductase
- MTBC0 PGAP product: adenosylcobalamin-dependent ribonucleoside-diphosphate reductase
- Pfam (hmmscan --cut_ga): ATP-cone PF03477.22 (E=2e-17), Ribonuc_red_lgN PF00317.27 (E=3e-18), Ribonuc_red_lgC PF02867.21 (E=1e-127)
- (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_215084.1)
- Domains: Pfam-A via hmmscan --cut_ga — ATP-cone (PF03477.22), Ribonuc_red_lgN (PF00317.27), Ribonuc_red_lgC (PF02867.21)
- 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
COG0209
- Curated reference: UniProt
P9WH77
(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 —
80 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000600|Rv0570|nrdZ
MGVSWPAKVRRRDGTLVPFDIARIEAAVTRAAREVACDDPDMPGTVAKAVADALGRGIAPVEDIQDCVEARLGEAGLDDVARVYIIYRQRRAELRTAKALLGVRDELKLSLAAVTVLRERYLLHDEQGRPAESTGELMDRSARCVAAAEDQYEPGSSRRWAERFATLLRNLEFLPNSPTLMNSGTDLGLLAGCFVLPIEDSLQSIFATLGQAAELQRAGGGTGYAFSHLRPAGDRVASTGGTASGPVSFLRLYDSAAGVVSMGGRRRGACMAVLDVSHPDICDFVTAKAESPSELPHFNLSVGVTDAFLRAVERNGLHRLVNPRTGKIVARMPAAELFDAICKAAHAGGDPGLVFLDTINRANPVPGRGRIEATNPCGEVPLLPYESCNLGSINLARMLADGRVDWDRLEEVAGVAVRFLDDVIDVSRYPFPELGEAARATRKIGLGVMGLAELLAALGIPYDSEEAVRLATRLMRRIQQAAHTASRRLAEERGAFPAFTDSRFARSGPRRNAQVTSVAPTGTISLIAGTTAGIEPMFAIAFTRAIVGRHLLEVNPCFDRLARDRGFYRDELIAEIAQRGGVRGYPRLPAEVRAAFPTAAEIAPQWHLRMQAAVQRHVEAAVSKTVNLPATATVDDVRAIYVAAWKAKVKGITVYRYGSREGQVLSYAAPKPLLAQADTEFSGGCAGRSCEF
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