MTBC Gene Atlas

pyrD Resolved · high auto-curated

H37Rv Rv2139 · MTBC0 mtbc0_002273 · 357 aa · 2425983–2427056 (+) · RefSeq NP_216655.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)dihydroorotate dehydrogenase
MTBC0 PGAP re-annotationquinone-dependent dihydroorotate dehydrogenase
Revised (this work)Quinone-dependent dihydroorotate dehydrogenase. Pfam: DHO_dh (PF01180.28).

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

Curated reference (UniProt)

UniProt P9WHL1 SwissProt · reviewed · Evidence at protein level
UniProt nameDihydroorotate dehydrogenase
EC (curated) EC 1.3.5.2
Curated functionCatalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namepyrD
eggNOG descriptionCatalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor
Orthologous groupCOG0167
EC number EC 1.3.5.2, EC 1.3.98.1
KEGG orthology K00226, K00254
KEGG pathways map00240, map01100
KEGG modules M00051
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.621 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 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
DHO_dhPF01180.28 2.1e-9549–336 Dihydroorotate dehydrogenase

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv1381 pyrC dihydroorotase 995 990 coexpression:858 database:900 textmining:529
Rv0382c pyrE orotate phosphoribosyltransferase 990 979 coexpression:734 database:900 textmining:590
Rv1937 oxygenase 969 958 coexpression:770 experimental:814
Rv0385 monooxygenase 958 953 coexpression:731 experimental:814
Rv1384 carB carbamoyl-phosphate synthase large subunit 949 917 coexpression:858 textmining:412
Rv1380 pyrB aspartate carbamoyltransferase 960 913 coexpression:857 textmining:571
Rv1383 carA carbamoyl-phosphate synthase small subunit 929 908 coexpression:849
Rv1385 pyrF orotidine 5'-phosphate decarboxylase 945 881 coexpression:861 textmining:563
Rv0383c ttfA hyp hypothetical protein 839 779 coexpression:730
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 800 776 coexpression:759
Rv1382 hyp hypothetical protein 795 768 coexpression:729
Rv1379 pyrR bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase 818 704 coexpression:654 textmining:413
Rv3396c guaA GMP synthase 807 586 textmining:554
Rv3858c gltD glutamate synthase small subunit 645 534
Rv0886 fprB ferredoxin/ferredoxin--NADP reductase 592 527

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: dihydroorotate dehydrogenase
  • MTBC0 PGAP product: quinone-dependent dihydroorotate dehydrogenase
  • Pfam (hmmscan --cut_ga): DHO_dh PF01180.28 (E=2e-95)
  • (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_216655.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DHO_dh (PF01180.28)
  • 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 COG0167
  • Curated reference: UniProt P9WHL1 (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_002273|Rv2139|pyrD
MYPLVRRLLFLIPPEHAHKLVFAVLRGVAAVAPVRRLLRRLLGPTDPVLASTVFGVRFPAPLGLAAGFDKDGTALSSWGAMGFGYAEIGTVTAHPQPGNPAPRLFRLADDRALLNRMGFNNHGARALAIRLARHRPEIPIGVNIGKTKKTPAGDAVNDYRASARMVGPLASYLVVNVSSPNTPGLRDLQAVESLRPILSAVRAETSTPVLVKIAPDLSDSDLDDIADLAVELDLAGIVATNTTVSRDGLTTPGVDRLGPGGISGPPLAQRAVQVLRRLYDRVGDRLALISVGGIETADDAWERITAGASLLQGYTGFIYGGERWAKDIHEGIARRLHDGGFGSLHEAVGSARRRQPS