pyrR Family assigned · medium auto-curated
H37Rv Rv1379 · MTBC0 mtbc0_001480 ·
193 aa · 1561998–1562579 (+) ·
RefSeq NP_215895.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional pyr operon transcriptional regulator/uracil phosphoribosyltransferase PyrR |
| Revised (this work) | Bifunctional pyr operon transcriptional regulator/uracil phosphoribosyltransferase PyrR. Pfam: Pribosyltran (PF00156.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHK3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional protein PyrR [Includes: Pyrimidine operon regulatory protein; Uracil phosphoribosyltransferase |
| EC (curated) |
EC 2.4.2.9
|
| Curated function | Regulates the transcription of the pyrimidine nucleotide (pyr) operon in response to exogenous pyrimidines..; FUNCTION: Also displays a weak uracil phosphoribosyltransferase activity which is not physiologically significant. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | pyrR |
| eggNOG description | Also displays a weak uracil phosphoribosyltransferase activity which is not physiologically significant |
| Orthologous group | COG2065 |
| EC number |
EC 2.4.2.9
|
| KEGG orthology |
K02825
|
| KEGG pathways |
map00240, map01100
|
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, GO:0030312, 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 2 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 |
|---|---|---|---|---|
Pribosyltran | PF00156.34 | 1.5e-16 | 25–167 | Phosphoribosyl transferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pyrB (aspartate carbamoyltransferase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1380 pyrB |
aspartate carbamoyltransferase | 998 | 997 ctx | neighborhood:882 cooccurence:727 coexpression:860 experimental:444 textmining:436 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 997 | 997 ctx | neighborhood:881 coexpression:776 database:900 |
Rv1381 pyrC |
dihydroorotase | 996 | 995 ctx | neighborhood:882 cooccurence:551 coexpression:852 experimental:444 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 982 | 976 ctx | neighborhood:882 coexpression:809 |
Rv1383 carA |
carbamoyl-phosphate synthase small subunit | 972 | 968 ctx | neighborhood:882 coexpression:736 |
Rv1382 hyp |
hypothetical protein | 964 | 960 ctx | neighborhood:882 coexpression:676 |
Rv2883c pyrH |
uridylate kinase | 935 | 916 | database:900 |
Rv3307 deoD |
purine nucleoside phosphorylase | 905 | 902 | database:900 |
Rv3314c deoA |
thymidine phosphorylase | 913 | 901 | database:900 |
Rv3309c upp |
uracil phosphoribosyltransferase | 989 | 900 | database:900 textmining:895 |
Rv0382c pyrE |
orotate phosphoribosyltransferase | 819 | 713 | coexpression:697 |
Rv0383c ttfA hyp |
hypothetical protein | 750 | 712 | coexpression:696 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 818 | 704 | coexpression:654 textmining:413 |
Rv1937 |
oxygenase | 688 | 671 | coexpression:647 |
Rv0385 |
monooxygenase | 685 | 665 | coexpression:646 |
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: bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase
- MTBC0 PGAP product: bifunctional pyr operon transcriptional regulator/uracil phosphoribosyltransferase PyrR
- Pfam (hmmscan --cut_ga): Pribosyltran PF00156.34 (E=1e-16)
- (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_215895.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pribosyltran (PF00156.34)
- 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
COG2065 - Curated reference: UniProt P9WHK3 (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 —
42 functional partner(s); context anchor
pyrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001480|Rv1379|pyrR MGAAGDAAIGRESRELMSAADVGRTISRIAHQIIEKTALDDPVGPDAPRVVLLGIPTRGVTLANRLAGNITEYSGIHVGHGALDITLYRDDLMIKPPRPLASTSIPAGGIDDALVILVDDVLYSGRSVRSALDALRDVGRPRAVQLAVLVDRGHRELPLRADYVGKNVPTSRSESVHVRLREHDGRDGVVISR