carA Family assigned · medium auto-curated
H37Rv Rv1383 · MTBC0 mtbc0_001484 ·
376 aa · 1565315–1566445 (+) ·
RefSeq NP_215899.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | carbamoyl-phosphate synthase small subunit |
|---|---|
| MTBC0 PGAP re-annotation | glutamine-hydrolyzing carbamoyl-phosphate synthase small subunit |
| Revised (this work) | Glutamine-hydrolyzing carbamoyl-phosphate synthase small subunit. Pfam: CPSase_sm_chain (PF00988.29), 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 |
P9WPK5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Carbamoyl phosphate synthase small chain |
| EC (curated) |
EC 6.3.5.5
|
| Curated function | Small subunit of the glutamine-dependent carbamoyl phosphate synthetase (CPSase). CPSase catalyzes the formation of carbamoyl phosphate from the ammonia moiety of glutamine, carbonate, and phosphate donated by ATP, constituting the first step of 2 biosynthetic pathways, one leading to arginine and/or urea and the other to pyrimidine nucleotides. The small subunit (glutamine amidotransferase) binds and cleaves glutamine to supply the large subunit with the substrate ammonia. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | carA |
| eggNOG description | Belongs to the CarA family |
| Orthologous group | COG0505 |
| EC number |
EC 6.3.5.5
|
| KEGG orthology |
K01956
|
| KEGG pathways |
map00240, map00250, map01100
|
| KEGG modules |
M00051
|
| Gene Ontology (45) |
GO:0000050, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005951, GO:0006082, GO:0006520, GO:0006525, GO:0006526, GO:0006807, GO:0008150 +33 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 | 1.046 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
CPSase_sm_chain | PF00988.29 | 5.2e-47 | 6–132 | Carbamoyl-phosphate synthase small chain, CPSase domain |
GATase | PF00117.35 | 5.8e-42 | 188–369 | Glutamine amidotransferase class-I |
Peptidase_C26 | PF07722.20 | 3.2e-07 | 240–352 | Peptidase C26 |
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:422 coexpression:865 database:900 textmining:449 |
Rv1381 pyrC |
dihydroorotase | 999 | 1000 ctx | neighborhood:882 fusion:900 coexpression:958 textmining:905 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:774 coexpression:967 experimental:928 database:900 textmining:453 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 989 | 988 ctx | neighborhood:881 coexpression:864 |
Rv1382 hyp |
hypothetical protein | 977 | 976 ctx | neighborhood:882 coexpression:805 |
Rv1379 pyrR |
bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase | 972 | 968 ctx | neighborhood:882 coexpression:736 |
Rv0808 purF |
amidophosphoribosyltransferase | 969 | 967 | coexpression:594 database:900 |
Rv3859c gltB |
glutamate synthase large subunit | 954 | 953 ctx | neighborhood:544 database:900 |
Rv1656 argF |
ornithine carbamoyltransferase | 957 | 951 ctx | fusion:550 coexpression:453 database:800 |
Rv0788 purQ |
phosphoribosylformylglycinamidine synthase | 949 | 947 | coexpression:463 database:900 |
Rv2222c glnA2 |
glutamine synthetase | 923 | 919 | database:900 |
Rv2220 glnA1 |
glutamine synthetase | 914 | 909 | database:900 |
Rv1878 glnA3 |
glutamine synthetase GlnA | 914 | 909 | database:900 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 929 | 908 | coexpression:849 |
Rv3436c glmS |
glucosamine--fructose-6-phosphate aminotransferase | 913 | 908 | database:900 |
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: carbamoyl-phosphate synthase small subunit
- MTBC0 PGAP product: glutamine-hydrolyzing carbamoyl-phosphate synthase small subunit
- Pfam (hmmscan --cut_ga): CPSase_sm_chain PF00988.29 (E=5e-47), GATase PF00117.35 (E=6e-42), Peptidase_C26 PF07722.20 (E=3e-07)
- (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_215899.1)
- Domains: Pfam-A via hmmscan --cut_ga — CPSase_sm_chain (PF00988.29), 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
COG0505 - Curated reference: UniProt P9WPK5 (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 —
70 functional partner(s); context anchor
pyrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001484|Rv1383|carA MSKAVLVLEDGRVFTGRPFGATGQALGEAVFSTGMSGYQETLTDPSYHRQIVVATAPQIGNTGWNGEDSESRGERIWVAGYAVRDPSPRASNWRATGTLEDELIRQRIVGIAGIDTRAVVRHLRSRGSMKAGVFSDGALAEPADLIARVRAQQSMLGADLAGEVSTAEPYVVEPDGPPGVSRFTVAALDLGIKTNTPRNFARRGIRCHVLPASTTFEQIAELNPHGVFLSNGPGDPATADHVVALTREVLGAGIPLFGICFGNQILGRALGLSTYKMVFGHRGINIPVVDHATGRVAVTAQNHGFALQGEAGQSFATPFGPAVVSHTCANDGVVEGVKLVDGRAFSVQYHPEAAAGPHDAEYLFDQFVELMAGEGR