pyrB Family assigned · medium auto-curated
H37Rv Rv1380 · MTBC0 mtbc0_001481 ·
319 aa · 1562576–1563535 (+) ·
RefSeq NP_215896.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | aspartate carbamoyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | aspartate carbamoyltransferase catalytic subunit |
| Revised (this work) | Aspartate carbamoyltransferase catalytic subunit. Pfam: OTCace_N (PF02729.27), OTCace (PF00185.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIT7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Aspartate carbamoyltransferase catalytic subunit |
| EC (curated) |
EC 2.1.3.2
|
| Curated function | Catalyzes the condensation of carbamoyl phosphate and aspartate to form carbamoyl aspartate and inorganic phosphate, the committed step in the de novo pyrimidine nucleotide biosynthesis pathway. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | pyrB |
| eggNOG description | Belongs to the ATCase OTCase family |
| Orthologous group | COG0540 |
| EC number |
EC 2.1.3.2
|
| KEGG orthology |
K00609
|
| KEGG pathways |
map00240, map00250, map01100
|
| KEGG modules |
M00051
|
| Gene Ontology (64) |
GO:0003674, GO:0003824, GO:0004070, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006139, GO:0006220 +52 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 | 0.297 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
OTCace_N | PF02729.27 | 1.0e-41 | 4–153 | Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain |
OTCace | PF00185.31 | 1.1e-19 | 160–305 | Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: carA (carbamoyl-phosphate synthase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1383 carA |
carbamoyl-phosphate synthase small subunit | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:422 coexpression:865 database:900 textmining:449 |
Rv1381 pyrC |
dihydroorotase | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:771 coexpression:958 experimental:915 database:900 textmining:815 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:508 coexpression:861 database:900 textmining:860 |
Rv1379 pyrR |
bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase | 998 | 997 ctx | neighborhood:882 cooccurence:727 coexpression:860 experimental:444 textmining:436 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 992 | 983 ctx | neighborhood:881 coexpression:859 textmining:588 |
Rv1382 hyp |
hypothetical protein | 981 | 975 ctx | neighborhood:882 coexpression:794 |
Rv1416 ribH |
6,7-dimethyl-8-ribityllumazine synthase | 948 | 948 | coexpression:945 |
Rv0357c purA |
adenylosuccinate synthetase | 943 | 926 | database:900 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 960 | 913 | coexpression:857 textmining:571 |
Rv2201 asnB |
asparagine synthetase | 922 | 910 | database:900 |
Rv1658 argG |
argininosuccinate synthase | 912 | 907 | database:900 |
Rv1595 nadB |
L-aspartate oxidase | 909 | 902 | database:900 |
Rv1538c ansA |
L-aparaginase | 906 | 902 | database:900 |
Rv1656 argF |
ornithine carbamoyltransferase | 861 | 840 | database:800 |
Rv3709c ask |
aspartokinase | 821 | 804 | database:800 |
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: aspartate carbamoyltransferase
- MTBC0 PGAP product: aspartate carbamoyltransferase catalytic subunit
- Pfam (hmmscan --cut_ga): OTCace_N PF02729.27 (E=1e-41), OTCace PF00185.31 (E=1e-19)
- (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_215896.1)
- Domains: Pfam-A via hmmscan --cut_ga — OTCace_N (PF02729.27), OTCace (PF00185.31)
- 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
COG0540 - Curated reference: UniProt P9WIT7 (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 —
87 functional partner(s); context anchor
carA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001481|Rv1380|pyrB MTPRHLLTAADLSRDDATAILDDADRFAQALVGRDIKKLPTLRGRTVVTMFYENSTRTRVSFEVAGKWMSADVINVSAAGSSVGKGESLRDTALTLRAAGADALIIRHPASGAAHLLAQWTGAHNDGPAVINAGDGTHEHPTQALLDALTIRQRLGGIEGRRIVIVGDILHSRVARSNVMLLDTLGAEVVLVAPPTLLPVGVTGWPATVSHDFDAELPAADAVLMLRVQAERMNGGFFPSVREYSVRYGLTERRQAMLPGHAVVLHPGPMVRGMEITSSVADSSQSAVLQQVSNGVQVRMAVLFHVLVGAQDAGKEGAA