pyrC Resolved · high auto-curated
H37Rv Rv1381 · MTBC0 mtbc0_001482 ·
430 aa · 1563532–1564824 (+) ·
RefSeq NP_215897.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dihydroorotase |
|---|---|
| MTBC0 PGAP re-annotation | dihydroorotase |
| Revised (this work) | Dihydroorotase. Pfam: DHOase (PF12890.14), Amidohydro_1 (PF01979.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHL3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydroorotase |
| EC (curated) |
EC 3.5.2.3
|
| Curated function | Catalyzes the reversible cyclization of carbamoyl aspartate to dihydroorotate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | pyrC |
| eggNOG description | Belongs to the metallo-dependent hydrolases superfamily. DHOase family. Class I DHOase subfamily |
| Orthologous group | COG0044 |
| EC number |
EC 3.5.2.3
|
| KEGG orthology |
K01465
|
| KEGG pathways |
map00240, map01100
|
| KEGG modules |
M00051
|
| Gene Ontology (42) |
GO:0003674, GO:0003824, GO:0004038, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006139, GO:0006144, GO:0006145, GO:0006725, GO:0006807 +30 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 | 0.204 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 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 |
|---|---|---|---|---|
DHOase | PF12890.14 | 1.2e-30 | 46–233 | Dihydro-orotase-like |
Amidohydro_1 | PF01979.27 | 1.7e-18 | 48–421 | Amidohydrolase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pyrB (aspartate carbamoyltransferase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1380 pyrB |
aspartate carbamoyltransferase | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:771 coexpression:958 experimental:915 database:900 textmining:815 |
Rv1383 carA |
carbamoyl-phosphate synthase small subunit | 999 | 1000 ctx | neighborhood:882 fusion:900 coexpression:958 textmining:905 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 999 | 999 ctx | neighborhood:882 fusion:900 coexpression:868 textmining:753 |
Rv1379 pyrR |
bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase | 996 | 995 ctx | neighborhood:882 cooccurence:551 coexpression:852 experimental:444 |
Rv1382 hyp |
hypothetical protein | 994 | 994 ctx | neighborhood:882 coexpression:953 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 995 | 990 | coexpression:858 database:900 textmining:529 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 991 | 987 ctx | neighborhood:881 coexpression:863 |
Rv0382c pyrE |
orotate phosphoribosyltransferase | 912 | 827 | coexpression:731 textmining:518 |
Rv0383c ttfA hyp |
hypothetical protein | 816 | 751 | coexpression:730 |
Rv1937 |
oxygenase | 817 | 745 | coexpression:728 |
Rv0385 |
monooxygenase | 757 | 725 | coexpression:709 |
Rv1377c |
transferase | 618 | 618 ctx | neighborhood:617 |
Rv2529 hyp |
hypothetical protein | 611 | 612 | database:546 |
Rv1378c hyp |
hypothetical protein | 606 | 606 ctx | neighborhood:604 |
Rv3275c purE |
5-(carboxyamino)imidazole ribonucleotide mutase | 616 | 576 | coexpression:426 |
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: dihydroorotase
- MTBC0 PGAP product: dihydroorotase
- Pfam (hmmscan --cut_ga): DHOase PF12890.14 (E=1e-30), Amidohydro_1 PF01979.27 (E=2e-18)
- (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_215897.1)
- Domains: Pfam-A via hmmscan --cut_ga — DHOase (PF12890.14), Amidohydro_1 (PF01979.27)
- 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
COG0044 - Curated reference: UniProt P9WHL3 (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 —
49 functional partner(s); context anchor
pyrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001482|Rv1381|pyrC MSVLIRGVRPYGEGERVDVLVDDGQIAQIGPDLAIPDTADVIDATGHVLLPGFVDLHTHLREPGREYAEDIETGSAAAALGGYTAVFAMANTNPVADSPVVTDHVWHRGQQVGLVDVHPVGAVTVGLAGAELTEMGMMNAGAAQVRMFSDDGVCVHDPLIMRRALEYATGLGVLIAQHAEEPRLTVGAVAHEGPMAARLGLAGWPRAAEESIVARDALLARDAGARVHICHASAAGTVEILKWAKDQGISITAEVTPHHLLLDDARLASYDGVNRVNPPLREASDAVALRQALADGIIDCVATDHAPHAEHEKCVEFAAARPGMLGLQTALSVVVQTMVAPGLLSWRDIARVMSENPACIARLPDQGRPLEVGEPANLTVVDPDATWTVTGADLASRSANTPFESMSLPATVTATLLRGKVTARDGKIRA