pyrG Resolved · high auto-curated
H37Rv Rv1699 · MTBC0 mtbc0_001807 ·
586 aa · 1935844–1937604 (+) ·
RefSeq NP_216215.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | CTP synthase |
|---|---|
| MTBC0 PGAP re-annotation | CTP synthase |
| Revised (this work) | CTP synthase. Pfam: CTP_synth_N (PF06418.21), GATase (PF00117.35), Peptidase_C26 (PF07722.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHK7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CTP synthase |
| EC (curated) |
EC 6.3.4.2
|
| Curated function | Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Is essential for M.tuberculosis growth in vitro and ex vivo. Regulates intracellular CTP levels through interactions with the four ribonucleotide triphosphates (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | pyrG |
| eggNOG description | Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Regulates intracellular CTP levels through interactions with the four ribonucleotide triphosphates |
| Orthologous group | COG0504 |
| EC number |
EC 6.3.4.2
|
| KEGG orthology |
K01937
|
| KEGG pathways |
map00240, map01100
|
| KEGG modules |
M00052
|
| Gene Ontology (8) |
GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, 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 | 0.336 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 6 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 |
|---|---|---|---|---|
CTP_synth_N | PF06418.21 | 5.9e-120 | 10–278 | CTP synthase N-terminus |
GATase | PF00117.35 | 5.8e-31 | 313–542 | Glutamine amidotransferase class-I |
Peptidase_C26 | PF07722.20 | 1.5e-05 | 379–526 | Peptidase C26 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1700 (NUDIX hydrolase), high confidence from genomic context alone (score 983 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1700 |
NUDIX hydrolase | 996 | 983 ctx | neighborhood:882 coexpression:862 textmining:817 |
Rv3396c guaA |
GMP synthase | 981 | 961 | coexpression:920 textmining:554 |
Rv1701 xerD |
tyrosine recombinase XerD | 990 | 932 ctx | neighborhood:882 coexpression:449 textmining:860 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 940 | 922 | database:900 |
Rv0321 dcd |
deoxycytidine triphosphate deaminase | 927 | 920 | database:900 |
Rv0719 rplF |
50S ribosomal protein L6 | 940 | 878 | coexpression:417 experimental:799 textmining:533 |
Rv0703 rplW |
50S ribosomal protein L23 | 887 | 870 | coexpression:414 experimental:788 |
Rv0716 rplE |
50S ribosomal protein L5 | 934 | 868 | coexpression:418 experimental:782 textmining:523 |
Rv0722 rpmD |
50S ribosomal protein L30 | 869 | 868 | coexpression:424 experimental:781 |
Rv3443c rplM |
50S ribosomal protein L13 | 917 | 836 | coexpression:499 experimental:684 textmining:518 |
Rv0720 rplR |
50S ribosomal protein L18 | 871 | 833 | experimental:766 |
Rv0715 rplX |
50S ribosomal protein L24 | 828 | 822 | experimental:738 |
Rv0651 rplJ |
50S ribosomal protein L10 | 841 | 819 | coexpression:704 experimental:414 |
Rv0714 rplN |
50S ribosomal protein L14 | 920 | 816 | experimental:766 textmining:586 |
Rv2890c rpsB |
30S ribosomal protein S2 | 905 | 814 | coexpression:773 textmining:514 |
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: CTP synthase
- MTBC0 PGAP product: CTP synthase
- Pfam (hmmscan --cut_ga): CTP_synth_N PF06418.21 (E=6e-120), GATase PF00117.35 (E=6e-31), Peptidase_C26 PF07722.20 (E=2e-05)
- (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_216215.1)
- Domains: Pfam-A via hmmscan --cut_ga — CTP_synth_N (PF06418.21), GATase (PF00117.35), Peptidase_C26 (PF07722.20)
- 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
COG0504 - Curated reference: UniProt P9WHK7 (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 —
175 functional partner(s); context anchor
Rv1700 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001807|Rv1699|pyrG MRKHPQTATKHLFVSGGVASSLGKGLTASSLGQLLTARGLHVTMQKLDPYLNVDPGTMNPFQHGEVFVTEDGAETDLDVGHYERFLDRNLPGSANVTTGQVYSTVIAKERRGEYLGDTVQVIPHITDEIKRRILAMAQPDADGNRPDVVITEIGGTVGDIESQPFLEAARQVRHYLGREDVFFLHVSLVPYLAPSGELKTKPTQHSVAALRSIGITPDALILRCDRDVPEALKNKIALMCDVDIDGVISTPDAPSIYDIPKVLHREELDAFVVRRLNLPFRDVDWTEWDDLLRRVHEPHETVRIALVGKYVELSDAYLSVAEALRAGGFKHRAKVEICWVASDGCETTSGAAAALGDVHGVLIPGGFGIRGIEGKIGAIAYARARGLPVLGLCLGLQCIVIEAARSVGLTNANSAEFDPDTPDPVIATMPDQEEIVAGEADLGGTMRLGSYPAVLEPDSVVAQAYQTTQVSERHRHRYEVNNAYRDKIAESGLRFSGTSPDGHLVEFVEYPPDRHPFVVGTQAHPELKSRPTRPHPLFVAFVGAAIDYKAGELLPVEIPEIPEHTPNGSSHRDGVGQPLPEPASRG