nrdF1 Family assigned · medium auto-curated

H37Rv Rv1981c · MTBC0 - · 322 aa · 2224220–2225188 (-) · RefSeq YP_177853.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonucleoside-diphosphate reductase subunit beta NrdF1
MTBC0 PGAP re-annotation
Revised (this work)Ribonucleoside-diphosphate reductase subunit beta NrdF1. Pfam: Ribonuc_red_sm (PF00268.28).

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 P9WH73 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonucleoside-diphosphate reductase subunit beta nrdF1
EC (curated) EC 1.17.4.1
Curated functionProvides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides (By similarity). Two genes for this protein are present in M.tuberculosis; this is thought to not be the active form. When coexpressed in E.coli with nrdE the 2 proteins do not complement a temperature-sensitive E.coli mutant, whereas the other gene (nrdF2) does complement.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namenrdF1
eggNOG descriptionProvides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
Orthologous groupCOG0208
EC number EC 1.17.4.1
KEGG orthology K00526
KEGG pathways map00230, map00240, map01100
KEGG modules M00053

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 0.295 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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)

PfamAccessioni-EvalueResiduesDescription
Ribonuc_red_smPF00268.28 1.4e-8812–283 Ribonucleotide reductase, small chain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: nrdE (ribonucleoside-diphosphate reductase subunit alpha), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3051c nrdE ribonucleoside-diphosphate reductase subunit alpha 998 997 ctx cooccurence:774 coexpression:663 experimental:600 database:900 textmining:595
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 989 986 coexpression:647 experimental:600 database:900
Rv3052c nrdI NrdI protein 992 975 ctx cooccurence:774 coexpression:460 experimental:788 textmining:693
Rv3048c nrdF2 ribonucleoside-diphosphate reductase subunit beta NrdF2 905 905 database:900
Rv3247c tmk thymidylate kinase 913 904 database:900
Rv1712 cmk cytidylate kinase 912 903 database:900
Rv0233 nrdB ribonucleoside-diphosphate reductase subunit beta NrdB 953 901 database:900 textmining:550
Rv0733 adk adenylate kinase 913 901 database:900
Rv2445c ndkA nucleoside diphosphate kinase 910 901 database:900
Rv1617 pykA pyruvate kinase 908 901 database:900
Rv1389 gmk guanylate kinase 907 901 database:900
Rv2583c relA bifunctional (p)ppGpp synthase/hydrolase RelA 901 900 database:900
Rv3053c nrdH glutaredoxin electron transport protein NrdH 924 826 ctx cooccurence:772 textmining:585
Rv2883c pyrH uridylate kinase 554 514 database:500
Rv1980c mpt64 immunogenic protein Mpt64 864 476 ctx neighborhood:468 textmining:752

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 beta NrdF1
  • Pfam (hmmscan --cut_ga): Ribonuc_red_sm PF00268.28 (E=1e-88)
  • (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 YP_177853.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ribonuc_red_sm (PF00268.28)
  • 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 COG0208
  • Curated reference: UniProt P9WH73 (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 — 34 functional partner(s); context anchor nrdE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1981c|nrdF1
MTGKLVERVHAINWNRLLDAKDLQVWERLTGNFWLPEKIPLSNDLASWQTLSSTEQQTTIRVFTGLTLLDTAQATVGAVAMIDDAVTPHEEAVLTNMAFMESVHAKSYSSIFSTLCSTKQIDDAFDWSEQNPYLQRKAQIIVDYYRGDDALKRKASSVMLESFLFYSGFYLPMYWSSRGKLTNTADLIRLIIRDEAVHGYYIGYKCQRGLADLTDAERADHREYTCELLHTLYANEIDYAHDLYDELGWTDDVLPYMRYNANKALANLGYQPAFDRDTCQVNPAVRAALDPGAGENHDFFSGSGSSYVMGTHQPTTDTDWDF