dut Resolved · high auto-curated

H37Rv Rv2697c · MTBC0 - · 154 aa · 3013683–3014147 (-) · RefSeq NP_217213.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)deoxyuridine 5'-triphosphate nucleotidohydrolase
MTBC0 PGAP re-annotation
Revised (this work)Deoxyuridine 5'-triphosphate nucleotidohydrolase. Pfam: dUTPase (PF00692.25), DCD (PF22769.2).

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 P9WNS5 SwissProt · reviewed · Evidence at protein level
UniProt nameDeoxyuridine 5'-triphosphate nucleotidohydrolase
EC (curated) EC 3.6.1.23
Curated functionThis enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namedut
eggNOG descriptionThis enzyme is involved in nucleotide metabolism it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA
Orthologous groupCOG0756
EC number EC 3.6.1.23
KEGG orthology K01520
KEGG pathways map00240, map00983, map01100
KEGG modules M00053
Gene Ontology (100) GO:0000287, GO:0003674, GO:0003824, GO:0004170, GO:0005488, GO:0006139, GO:0006220, GO:0006221, GO:0006226, GO:0006244, GO:0006725, GO:0006753 +88 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 0.389 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 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
dUTPasePF00692.25 8.9e-2715–149 dUTPase
DCDPF22769.2 2.4e-1332–118 dCTP deaminase-like

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

Closest characterised functional partner: Rv2698 (transmembrane protein), high confidence from genomic context alone (score 793 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1252c lprE lipoprotein LprE 964 963 experimental:837 database:782
Rv2764c thyA thymidylate synthase ThyA 986 951 coexpression:445 database:900 textmining:739
Rv3247c tmk thymidylate kinase 949 929 database:900
Rv2445c ndkA nucleoside diphosphate kinase 956 914 database:900 textmining:513
Rv2754c thyX thymidylate synthase ThyX 993 908 database:900 textmining:934
Rv0321 dcd deoxycytidine triphosphate deaminase 930 908 database:900
Rv2698 transmembrane protein 793 793 ctx neighborhood:790
Rv2696c hyp hypothetical protein 793 793 ctx neighborhood:790
Rv2116 lppK lipoprotein LppK 743 718 coexpression:709
Rv0002 dnaN DNA polymerase III subunit beta 743 718 coexpression:709
Rv2737c recA recombinase A 792 707 coexpression:414 database:457
Rv1391 dfp bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase 716 699 coexpression:674
Rv0252 nirB nitrite reductase large subunit NirB 685 673 ctx fusion:673
Rv3051c nrdE ribonucleoside-diphosphate reductase subunit alpha 703 663 coexpression:644
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 703 663 coexpression:644

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): deoxyuridine 5'-triphosphate nucleotidohydrolase
  • Pfam (hmmscan --cut_ga): dUTPase PF00692.25 (E=9e-27), DCD PF22769.2 (E=2e-13)
  • (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_217213.1)
  • Domains: Pfam-A via hmmscan --cut_ga — dUTPase (PF00692.25), DCD (PF22769.2)
  • 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 COG0756
  • Curated reference: UniProt P9WNS5 (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 — 37 functional partner(s); context anchor Rv2698
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2697c|dut
MSTTLAIVRLDPGLPLPSRAHDGDAGVDLYSAEDVELAPGRRALVRTGVAVAVPFGMVGLVHPRSGLATRVGLSIVNSPGTIDAGYRGEIKVALINLDPAAPIVVHRGDRIAQLLVQRVELVELVEVSSFDEAGLASTSRGDGGHGSSGGHASL