carB Family assigned · medium auto-curated
H37Rv Rv1384 · MTBC0 - ·
1115 aa · 1557101–1560448 (+) ·
RefSeq YP_177804.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | carbamoyl-phosphate synthase large subunit |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Carbamoyl-phosphate synthase large subunit. Pfam: CPSase_L_D2 (PF02786.23), CPSase_L_D3 (PF02787.26), CPSase_L_D1 (PF25596.2), Dala_Dala_lig_C (PF07478.19), ATP-grasp (PF02222.28), MGS (PF02142.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WPK3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Carbamoyl phosphate synthase large chain |
| EC (curated) |
EC 6.3.4.16, EC 6.3.5.5
|
| Curated function | Large 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 large subunit (synthetase) binds the substrates ammonia (free or transferred from glutamine from the small subunit), hydrogencarbonate and ATP and carries out an ATP-coupled ligase reaction, activating hydrogencarbonate by forming carboxy phosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | carB |
| eggNOG description | Carbamoyl-phosphate synthetase ammonia chain |
| Orthologous group | COG0458 |
| EC number |
EC 6.3.5.5
|
| KEGG orthology |
K01955
|
| KEGG pathways |
map00240, map00250, map01100
|
| KEGG modules |
M00051
|
| Gene Ontology (50) |
GO:0000050, GO:0003674, GO:0003824, GO:0004087, GO:0004088, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006520 +38 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 | 0.4 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 13 synonymous, 15 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_L_D2 | PF02786.23 | 2.4e-65 | 133–339 | Carbamoyl-phosphate synthase L chain, ATP binding domain |
CPSase_L_D3 | PF02787.26 | 3.3e-21 | 429–505 | Carbamoyl-phosphate synthetase large chain, oligomerisation domain |
CPSase_L_D1 | PF25596.2 | 6.4e-44 | 565–684 | Carbamoyl phosphate synthase preATP-grasp domain |
Dala_Dala_lig_C | PF07478.19 | 1.6e-05 | 695–856 | D-ala D-ala ligase C-terminus |
ATP-grasp | PF02222.28 | 5.2e-08 | 696–860 | ATP-grasp domain |
MGS | PF02142.28 | 8.7e-23 | 986–1078 | MGS-like 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:774 coexpression:967 experimental:928 database:900 textmining:453 |
Rv1380 pyrB |
aspartate carbamoyltransferase | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:508 coexpression:861 database:900 textmining:860 |
Rv1381 pyrC |
dihydroorotase | 999 | 999 ctx | neighborhood:882 fusion:900 coexpression:868 textmining:753 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 998 | 997 ctx | neighborhood:881 fusion:653 coexpression:918 textmining:419 |
Rv1382 hyp |
hypothetical protein | 996 | 995 ctx | neighborhood:882 coexpression:793 experimental:829 |
Rv1658 argG |
argininosuccinate synthase | 995 | 988 ctx | fusion:720 coexpression:794 database:800 textmining:651 |
Rv1656 argF |
ornithine carbamoyltransferase | 992 | 979 ctx | fusion:818 coexpression:431 database:800 textmining:657 |
Rv1379 pyrR |
bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase | 982 | 976 ctx | neighborhood:882 coexpression:809 |
Rv0808 purF |
amidophosphoribosyltransferase | 981 | 975 | coexpression:665 database:900 |
Rv3859c gltB |
glutamate synthase large subunit | 991 | 971 ctx | neighborhood:544 coexpression:407 database:900 textmining:730 |
Rv3436c glmS |
glucosamine--fructose-6-phosphate aminotransferase | 937 | 919 | database:900 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 949 | 917 | coexpression:858 textmining:412 |
Rv2222c glnA2 |
glutamine synthetase | 923 | 917 | database:900 |
Rv0788 purQ |
phosphoribosylformylglycinamidine synthase | 933 | 910 | database:900 |
Rv3858c gltD |
glutamate synthase small subunit | 930 | 907 | 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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): carbamoyl-phosphate synthase large subunit
- Pfam (hmmscan --cut_ga): CPSase_L_D2 PF02786.23 (E=2e-65), CPSase_L_D3 PF02787.26 (E=3e-21), CPSase_L_D1 PF25596.2 (E=6e-44), Dala_Dala_lig_C PF07478.19 (E=2e-05), ATP-grasp PF02222.28 (E=5e-08), MGS PF02142.28 (E=9e-23)
- (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 YP_177804.1)
- Domains: Pfam-A via hmmscan --cut_ga — CPSase_L_D2 (PF02786.23), CPSase_L_D3 (PF02787.26), CPSase_L_D1 (PF25596.2), Dala_Dala_lig_C (PF07478.19), ATP-grasp (PF02222.28), MGS (PF02142.28)
- 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
COG0458 - Curated reference: UniProt P9WPK3 (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 —
94 functional partner(s); context anchor
carA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1384|carB MPRRTDLHHVLVIGSGPIVIGQACEFDYSGTQACRVLRAEGLQVSLVNSNPATIMTDPEFADHTYVEPITPAFVERVIAQQAERGNKIDALLATLGGQTALNTAVALYESGVLEKYGVELIGADFDAIQRGEDRQRFKDIVAKAGGESARSRVCFTMAEVRETVAELGLPVVVRPSFTMGGLGSGIAYSTDEVDRMAGAGLAASPSANVLIEESIYGWKEFELELMRDGHDNVVVVCSIENVDPMGVHTGDSVTVAPAMTLTDREYQRMRDLGIAILREVGVDTGGCNIQFAVNPRDGRLIVIEMNPRVSRSSALASKATGFPIAKIAAKLAIGYTLDEIVNDITGETPACFEPTLDYVVVKAPRFAFEKFPGADPTLTTTMKSVGEAMSLGRNFVEALGKVMRSLETTRAGFWTAPDPDGGIEEALTRLRTPAEGRLYDIELALRLGATVERVAEASGVDPWFIAQINELVNLRNELVAAPVLNAELLRRAKHSGLSDHQIASLRPELAGEAGVRSLRVRLGIHPVYKTVDTCAAEFEAQTPYHYSSYELDPAAETEVAPQTERPKVLILGSGPNRIGQGIEFDYSCVHAATTLSQAGFETVMVNCNPETVSTDYDTADRLYFEPLTFEDVLEVYHAEMESGSGGPGVAGVIVQLGGQTPLGLAHRLADAGVPIVGTPPEAIDLAEDRGAFGDLLSAAGLPAPKYGTATTFAQARRIAEEIGYPVLVRPSYVLGGRGMEIVYDEETLQGYITRATQLSPEHPVLVDRFLEDAVEIDVDALCDGAEVYIGGIMEHIEEAGIHSGDSACALPPVTLGRSDIAKVRKATEAIAHGIGVVGLLNVQYALKDDVLYVLEANPRASRTVPFVSKATAVPLAKACARIMLGATIAQLRAEGLLAVTGDGAHAARNAPIAVKEAVLPFHRFRRADGAAIDSLLGPEMKSTGEVMGIDRDFGSAFAKSQTAAYGSLPAQGTVFVSVANRDKRSLVFPVKRLADLGFRVLATEGTAEMLRRNGIPCDDVRKHFEPAQPGRPTMSAVDAIRAGEVNMVINTPYGNSGPRIDGYEIRSAAVAGNIPCITTVQGASAAVQGIEAGIRGDIGVRSLQELHRVIGGVER