ID CARB_STRA5 Reviewed; 1060 AA. AC Q8DZQ7; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 120. DE RecName: Full=Carbamoyl phosphate synthase large chain {ECO:0000255|HAMAP-Rule:MF_01210}; DE EC=6.3.4.16 {ECO:0000255|HAMAP-Rule:MF_01210}; DE EC=6.3.5.5 {ECO:0000255|HAMAP-Rule:MF_01210}; DE AltName: Full=Carbamoyl phosphate synthetase ammonia chain {ECO:0000255|HAMAP-Rule:MF_01210}; GN Name=carB {ECO:0000255|HAMAP-Rule:MF_01210}; GN OrderedLocusNames=SAG1042; OS Streptococcus agalactiae serotype V (strain ATCC BAA-611 / 2603 V/R). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Streptococcus. OX NCBI_TaxID=208435; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-611 / 2603 V/R; RX PubMed=12200547; DOI=10.1073/pnas.182380799; RA Tettelin H., Masignani V., Cieslewicz M.J., Eisen J.A., Peterson S.N., RA Wessels M.R., Paulsen I.T., Nelson K.E., Margarit I., Read T.D., RA Madoff L.C., Wolf A.M., Beanan M.J., Brinkac L.M., Daugherty S.C., RA DeBoy R.T., Durkin A.S., Kolonay J.F., Madupu R., Lewis M.R., Radune D., RA Fedorova N.B., Scanlan D., Khouri H.M., Mulligan S., Carty H.A., RA Cline R.T., Van Aken S.E., Gill J., Scarselli M., Mora M., Iacobini E.T., RA Brettoni C., Galli G., Mariani M., Vegni F., Maione D., Rinaudo D., RA Rappuoli R., Telford J.L., Kasper D.L., Grandi G., Fraser C.M.; RT "Complete genome sequence and comparative genomic analysis of an emerging RT human pathogen, serotype V Streptococcus agalactiae."; RL Proc. Natl. Acad. Sci. U.S.A. 99:12391-12396(2002). CC -!- FUNCTION: Large subunit of the glutamine-dependent carbamoyl phosphate CC synthetase (CPSase). CPSase catalyzes the formation of carbamoyl CC phosphate from the ammonia moiety of glutamine, carbonate, and CC phosphate donated by ATP, constituting the first step of 2 biosynthetic CC pathways, one leading to arginine and/or urea and the other to CC pyrimidine nucleotides. The large subunit (synthetase) binds the CC substrates ammonia (free or transferred from glutamine from the small CC subunit), hydrogencarbonate and ATP and carries out an ATP-coupled CC ligase reaction, activating hydrogencarbonate by forming carboxy CC phosphate which reacts with ammonia to form carbamoyl phosphate. CC {ECO:0000255|HAMAP-Rule:MF_01210}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 ATP + H2O + hydrogencarbonate + L-glutamine = 2 ADP + CC carbamoyl phosphate + 2 H(+) + L-glutamate + phosphate; CC Xref=Rhea:RHEA:18633, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58228, ChEBI:CHEBI:58359, CC ChEBI:CHEBI:456216; EC=6.3.5.5; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01210}; CC -!- CATALYTIC ACTIVITY: [Carbamoyl phosphate synthase large chain]: CC Reaction=2 ATP + hydrogencarbonate + NH4(+) = 2 ADP + carbamoyl CC phosphate + 2 H(+) + phosphate; Xref=Rhea:RHEA:18029, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58228, CC ChEBI:CHEBI:456216; EC=6.3.4.16; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01210}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01210}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01210}; CC Note=Binds 4 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000255|HAMAP- CC Rule:MF_01210}; CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; carbamoyl CC phosphate from bicarbonate: step 1/1. {ECO:0000255|HAMAP- CC Rule:MF_01210}. CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; CC (S)-dihydroorotate from bicarbonate: step 1/3. {ECO:0000255|HAMAP- CC Rule:MF_01210}. CC -!- SUBUNIT: Composed of two chains; the small (or glutamine) chain CC promotes the hydrolysis of glutamine to ammonia, which is used by the CC large (or ammonia) chain to synthesize carbamoyl phosphate. Tetramer of CC heterodimers (alpha,beta)4. {ECO:0000255|HAMAP-Rule:MF_01210}. CC -!- DOMAIN: The large subunit is composed of 2 ATP-grasp domains that are CC involved in binding the 2 ATP molecules needed for carbamoyl phosphate CC synthesis. The N-terminal ATP-grasp domain (referred to as the CC carboxyphosphate synthetic component) catalyzes the ATP-dependent CC phosphorylation of hydrogencarbonate to carboxyphosphate and the CC subsequent nucleophilic attack by ammonia to form a carbamate CC intermediate. The C-terminal ATP-grasp domain (referred to as the CC carbamoyl phosphate synthetic component) then catalyzes the CC phosphorylation of carbamate with the second ATP to form the end CC product carbamoyl phosphate. The reactive and unstable enzyme CC intermediates are sequentially channeled from one active site to the CC next through the interior of the protein over a distance of at least 96 CC A. {ECO:0000255|HAMAP-Rule:MF_01210}. CC -!- SIMILARITY: Belongs to the CarB family. {ECO:0000255|HAMAP- CC Rule:MF_01210}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE009948; AAM99924.1; -; Genomic_DNA. DR RefSeq; NP_688052.1; NC_004116.1. DR RefSeq; WP_001126466.1; NC_004116.1. DR AlphaFoldDB; Q8DZQ7; -. DR SMR; Q8DZQ7; -. DR STRING; 208435.SAG1042; -. DR KEGG; sag:SAG1042; -. DR PATRIC; fig|208435.3.peg.1053; -. DR HOGENOM; CLU_000513_1_2_9; -. DR OrthoDB; 9804197at2; -. DR UniPathway; UPA00068; UER00171. DR UniPathway; UPA00070; UER00115. DR Proteomes; UP000000821; Chromosome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0004087; F:carbamoyl-phosphate synthase (ammonia) activity; IEA:RHEA. DR GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006526; P:arginine biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd01424; MGS_CPS_II; 1. DR Gene3D; 3.40.50.20; -; 2. DR Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1. DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 2. DR Gene3D; 1.10.1030.10; Carbamoyl-phosphate synthetase, large subunit oligomerisation domain; 1. DR Gene3D; 3.40.50.1380; Methylglyoxal synthase-like domain; 1. DR HAMAP; MF_01210_A; CPSase_L_chain_A; 1. DR HAMAP; MF_01210_B; CPSase_L_chain_B; 1. DR InterPro; IPR011761; ATP-grasp. DR InterPro; IPR013815; ATP_grasp_subdomain_1. DR InterPro; IPR006275; CarbamoylP_synth_lsu. DR InterPro; IPR005480; CarbamoylP_synth_lsu_oligo. DR InterPro; IPR036897; CarbamoylP_synth_lsu_oligo_sf. DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd. DR InterPro; IPR005483; CbamoylP_synth_lsu_CPSase_dom. DR InterPro; IPR011607; MGS-like_dom. DR InterPro; IPR036914; MGS-like_dom_sf. DR InterPro; IPR033937; MGS_CPS_CarB. DR InterPro; IPR016185; PreATP-grasp_dom_sf. DR NCBIfam; TIGR01369; CPSaseII_lrg; 1. DR PANTHER; PTHR11405:SF5; CAD PROTEIN; 1. DR PANTHER; PTHR11405; CARBAMOYLTRANSFERASE FAMILY MEMBER; 1. DR Pfam; PF02786; CPSase_L_D2; 2. DR Pfam; PF02787; CPSase_L_D3; 1. DR Pfam; PF02142; MGS; 1. DR PRINTS; PR00098; CPSASE. DR SMART; SM01096; CPSase_L_D3; 1. DR SMART; SM01209; GARS_A; 1. DR SMART; SM00851; MGS; 1. DR SUPFAM; SSF48108; Carbamoyl phosphate synthetase, large subunit connection domain; 1. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 2. DR SUPFAM; SSF52335; Methylglyoxal synthase-like; 1. DR SUPFAM; SSF52440; PreATP-grasp domain; 2. DR PROSITE; PS50975; ATP_GRASP; 2. DR PROSITE; PS00866; CPSASE_1; 2. DR PROSITE; PS00867; CPSASE_2; 2. DR PROSITE; PS51855; MGS; 1. PE 3: Inferred from homology; KW Amino-acid biosynthesis; Arginine biosynthesis; ATP-binding; Ligase; KW Magnesium; Manganese; Metal-binding; Nucleotide-binding; KW Pyrimidine biosynthesis; Reference proteome; Repeat. FT CHAIN 1..1060 FT /note="Carbamoyl phosphate synthase large chain" FT /id="PRO_0000145048" FT DOMAIN 133..327 FT /note="ATP-grasp 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT DOMAIN 671..861 FT /note="ATP-grasp 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT DOMAIN 930..1060 FT /note="MGS-like" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 1..401 FT /note="Carboxyphosphate synthetic domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 402..546 FT /note="Oligomerization domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 547..929 FT /note="Carbamoyl phosphate synthetic domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 930..1060 FT /note="Allosteric domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 129 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 169 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 175 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 176 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 208 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 210 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 215 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 241 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 242 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 243 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 284 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 284 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 284 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 300 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 300 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 707 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 746 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 748 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 752 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 777 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 778 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 779 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 780 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 820 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 820 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 820 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 832 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 832 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 832 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 832 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 832 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" SQ SEQUENCE 1060 AA; 117093 MW; 04C6D2B617E08274 CRC64; MPKRTDIRKI MVIGSGPIVI GQAAEFDYSG TQACLSLKEE GYQVVLVNSN PATIMTDKDI ADKVYIEPIT LEFVTRILRK ERPDALLPTL GGQTGLNMAM ALSKNGILEE LNVELLGTKL SAIDKAEDRD LFKQLMEELN QPIPESEIVN SVEEAIQFAE QIGYPLIVRP AFTLGGTGGG MCDNQEQLVD ITTKGLKLSP VTQCLIERSI AGFKEIEYEV MRDAADNALV VCNMENFDPV GIHTGDSIVF APAQTLSDVE NQLLRDASLD IIRALKIEGG CNVQLALDPN SFKYYVIEVN PRVSRSSALA SKATGYPIAK LAAKIAVGLT LDEVINPITK TTYAMFEPAL DYVVAKMPRF PFDKFESGDR KLGTQMKATG EVMAIGRNIE ESLLKACRSL EIGVDHIKIA DLDNVSDDVL LEKIRKAEDD RLFYLAEALR RHYSIEKLAS LTSIDSFFLD KLRVIVELED LLSKNRLDIN ILKKVKNKGF SDKAIASLWQ INEDQVRNMR KEAGILPVYK MVDTCASEFD SATPYFYSTY AVENESLISD KASILVLGSG PIRIGQGVEF DYATVHSVKA IRESGFEAII MNSNPETVST DFSISDKLYF EPLTFEDVMN VIDLEKPEGV ILQFGGQTAI NLAKDLNKAG VKILGTQLED LDRAENRKQF EATLQALNIP QPPGFTATTE EEAVNAAQKI GYPVLVRPSY VLGGRAMKIV ENEEDLRHYM TTAVKASPDH PVLIDAYLIG KECEVDAISD GQNILIPGIM EHIERSGVHS GDSMAVYPPQ TLSETIIETI VDYTKRLAIG LNCIGMMNIQ FVIKDQKVYV IEVNPRASRT LPFLSKVTHI PMAQVATKVI LGDKLCNFTY GYDLYPASDM VHIKAPVFSF TKLAKVDSLL GPEMKSTGEV MGSDINLQKA LYKAFEAAYL HMPDYGNIVF TVDDTDKEEA LELAKVYQSI GYRIYATQGT AIYFDANGLE TVLVGKLGEN DRNHIPDLIK NGKIQAVINT VGQNNIDNHD ALIIRRSAIE QGVPLFTSLD TAHAMFKVLE SRAFTLKVLD //