dcd Resolved · high auto-curated

H37Rv Rv0321 · MTBC0 mtbc0_000342 · 190 aa · 391905–392477 (+) · RefSeq NP_214835.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)deoxycytidine triphosphate deaminase
MTBC0 PGAP re-annotationdCTP deaminase
Revised (this work)DCTP deaminase. Pfam: DCD (PF22769.2), DCD_N (PF06559.17), DCD_C (PF22569.2), dUTPase (PF00692.25).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WP17 SwissProt · reviewed · Evidence at protein level
UniProt namedCTP deaminase, dUMP-forming
EC (curated) EC 3.5.4.30
Curated functionBifunctional enzyme that catalyzes both the deamination of dCTP to dUTP and the hydrolysis of dUTP to dUMP without releasing the toxic dUTP intermediate. It also acts as a dUTP diphosphatase. Affinity for dCTP and dUTP are very similar.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namedcd
eggNOG descriptionBelongs to the dCTP deaminase family
Orthologous groupCOG0717
EC number EC 3.5.4.13
KEGG orthology K01494
KEGG pathways map00240, map01100
KEGG modules M00053
Gene Ontology (12) GO:0003674, GO:0003824, GO:0004170, GO:0016462, GO:0016787, GO:0016810, GO:0016814, GO:0016817, GO:0016818, GO:0019239, GO:0033973, GO:0047429

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 1.038 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
DCDPF22769.2 8.4e-432–151 dCTP deaminase-like
DCD_NPF06559.17 5.2e-073–151 2'-deoxycytidine 5'-triphosphate deaminase (DCD) N-terminal domain
DCD_CPF22569.2 4.5e-0864–175 2'-deoxycytidine 5'-triphosphate deaminase (DCD), C-terminal domain
dUTPasePF00692.25 1.5e-0772–163 dUTPase

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

Closest characterised functional partner: udgA (UDP-glucose 6-dehydrogenase UdgA), medium confidence from genomic context alone (score 611 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1699 pyrG CTP synthase 927 920 database:900
Rv2445c ndkA nucleoside diphosphate kinase 926 915 database:900
Rv2697c dut deoxyuridine 5'-triphosphate nucleotidohydrolase 930 908 database:900
Rv0320 hyp hypothetical protein 702 703 ctx neighborhood:700
Rv3266c rmlD dTDP-4-dehydrorhamnose reductase 645 645 coexpression:645
Rv0322 udgA UDP-glucose 6-dehydrogenase UdgA 612 611 ctx neighborhood:611
Rv0319 pcp pyrrolidone-carboxylate peptidase 560 560 ctx neighborhood:560
Rv3628 ppa inorganic pyrophosphatase 494 465
Rv2965c kdtB phosphopantetheine adenylyltransferase 455 456 coexpression:456
Rv0318c integral membrane protein 413 413 ctx neighborhood:410
Rv0382c pyrE orotate phosphoribosyltransferase 463 248
Rv2754c thyX thymidylate synthase ThyX 517 156 textmining:452
Rv2764c thyA thymidylate synthase ThyA 486 154 textmining:418
Rv3247c tmk thymidylate kinase 477 123 textmining:428
Rv0524 hemL glutamate-1-semialdehyde 2,1-aminomutase 677 97 textmining:658

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: deoxycytidine triphosphate deaminase
  • MTBC0 PGAP product: dCTP deaminase
  • Pfam (hmmscan --cut_ga): DCD PF22769.2 (E=8e-43), DCD_N PF06559.17 (E=5e-07), DCD_C PF22569.2 (E=4e-08), dUTPase PF00692.25 (E=1e-07)
  • (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_214835.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DCD (PF22769.2), DCD_N (PF06559.17), DCD_C (PF22569.2), dUTPase (PF00692.25)
  • 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 COG0717
  • Curated reference: UniProt P9WP17 (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 — 23 functional partner(s); context anchor udgA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000342|Rv0321|dcd
MLLSDRDLRAEISSGRLGIDPFDDTLVQPSSIDVRLDCLFRVFNNTRYTHIDPAKQQDELTSLVQPVDGEPFVLHPGEFVLGSTLELFTLPDNLAGRLEGKSSLGRLGLLTHSTAGFIDPGFSGHITLELSNVANLPITLWPGMKIGQLCMLRLTSPSEHPYGSSRAGSKYQGQRGPTPSRSYQNFIRST