nrdE Family assigned · medium auto-curated
H37Rv Rv3051c · MTBC0 - ·
693 aa · 3412085–3414166 (-) ·
RefSeq NP_217567.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonucleoside-diphosphate reductase subunit alpha |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Ribonucleoside-diphosphate reductase subunit alpha. Pfam: RNR_N (PF08343.16), 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.
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 |
P9WH75
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonucleoside-diphosphate reductase subunit alpha |
| EC (curated) |
EC 1.17.4.1
|
| Curated function | Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. When coexpressed in E.coli with nrdF2 the 2 proteins complement a temperature-sensitive E.coli mutant, however coexpression with nrdF1 does not complement. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | nrdE |
| eggNOG description | Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides |
| Orthologous group | COG0209 |
| EC number |
EC 1.17.4.1
|
| KEGG orthology |
K00525
|
| KEGG pathways |
map00230, map00240, map01100
|
| KEGG modules |
M00053
|
| Gene Ontology (84) |
GO:0000166, GO:0003674, GO:0003824, GO:0004748, GO:0005488, GO:0005524, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +72 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 | 0.237 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 4 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 |
|---|---|---|---|---|
RNR_N | PF08343.16 | 2.3e-27 | 1–76 | Ribonucleotide reductase N-terminal |
Ribonuc_red_lgN | PF00317.27 | 2.2e-16 | 78–151 | Ribonucleotide reductase, all-alpha domain |
Ribonuc_red_lgC | PF02867.21 | 4.0e-160 | 155–673 | Ribonucleotide reductase, barrel domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nrdF2 (ribonucleoside-diphosphate reductase subunit beta NrdF2), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3048c nrdF2 |
ribonucleoside-diphosphate reductase subunit beta NrdF2 | 999 | 997 ctx | cooccurence:774 coexpression:666 experimental:600 database:900 textmining:861 |
Rv3053c nrdH |
glutaredoxin electron transport protein NrdH | 998 | 997 ctx | neighborhood:564 cooccurence:772 coexpression:872 database:614 textmining:696 |
Rv1981c nrdF1 |
ribonucleoside-diphosphate reductase subunit beta NrdF1 | 998 | 997 ctx | cooccurence:774 coexpression:663 experimental:600 database:900 textmining:595 |
Rv3052c nrdI |
NrdI protein | 999 | 993 ctx | neighborhood:633 cooccurence:773 coexpression:924 textmining:896 |
Rv0233 nrdB |
ribonucleoside-diphosphate reductase subunit beta NrdB | 993 | 985 | coexpression:648 experimental:600 database:900 textmining:604 |
Rv0038 hyp |
hypothetical protein | 969 | 966 | coexpression:560 experimental:789 database:662 |
Rv3247c tmk |
thymidylate kinase | 943 | 923 | database:900 |
Rv1712 cmk |
cytidylate kinase | 922 | 913 | database:900 |
Rv0570 nrdZ |
vitamin B12-dependent ribonucleoside-diphosphate reductase | 915 | 907 | database:900 |
Rv0733 adk |
adenylate kinase | 915 | 903 | database:900 |
Rv1617 pykA |
pyruvate kinase | 907 | 902 | database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 912 | 901 | database:900 |
Rv1389 gmk |
guanylate kinase | 911 | 901 | database:900 |
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA | 905 | 901 | database:900 |
Rv3050c |
AsnC family transcriptional regulator | 889 | 890 ctx | neighborhood:557 coexpression:761 |
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): ribonucleoside-diphosphate reductase subunit alpha
- Pfam (hmmscan --cut_ga): RNR_N PF08343.16 (E=2e-27), Ribonuc_red_lgN PF00317.27 (E=2e-16), Ribonuc_red_lgC PF02867.21 (E=4e-160)
- (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_217567.1)
- Domains: Pfam-A via hmmscan --cut_ga — RNR_N (PF08343.16), 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 P9WH75 (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 —
56 functional partner(s); context anchor
nrdF2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3051c|nrdE MLNLYDADGKIQFDKDREAAHQYFLQHVNQNTVFFHNQDEKLDYLIRENYYEREVLDQYSRNFVKTLLDRAYAKKFRFPTFLGAFKYYTSYTLKTFDGKRYLERFEDRVVMVALTLAAGDTALAELLVDEIIDGRFQPATPTFLNSGKKQRGEPVSCFLLRVEDNMESIGRSINSALQLSKRGGGVALLLTNIREHGAPIKNIENQSSGVIPIMKLLEDAFSYANQLGARQGAGAVYLHAHHPDIYRFLDTKRENADEKIRIKTLSLGVVIPDITFELAKRNDDMYLFSPYDVERVYGVPFADISVTEKYYEMVDDARIRKTKIKAREFFQTLAELQFESGYPYIMFEDTVNRANPIDGKITHSNLCSEILQVSTPSLFNEDLSYAKVGKDISCNLGSLNIAKTMDSPDFAQTIEVAIRALTAVSDQTHIKSVPSIEQGNNDSHAIGLGQMNLHGYLARERIFYGSDEGIDFTNIYFYTVLYHALRASNRIAIERGTHFKGFERSKYASGEFFDKYTDQIWEPKTQKVRQLFADAGIRIPTQDDWRRLKESVQAHGIYNQNLQAVPPTGSISYINHSTSSIHPIVSKVEIRKEGKIGRVYYPAPYMTNDNLEYYEDAYEIGYEKIIDTYAAATQHVDQGLSLTLFFKDTATTRDVNKAQIYAWRKGIKTLYYIRLRQMALEGTEVEGCVSCML