ID A0A0F2NIS3_9FIRM Unreviewed; 1076 AA. AC A0A0F2NIS3; DT 24-JUN-2015, integrated into UniProtKB/TrEMBL. DT 24-JUN-2015, sequence version 1. DT 29-MAY-2024, entry version 41. DE RecName: Full=Carbamoyl phosphate synthase large chain {ECO:0000256|HAMAP-Rule:MF_01210}; DE EC=6.3.4.16 {ECO:0000256|HAMAP-Rule:MF_01210}; DE EC=6.3.5.5 {ECO:0000256|HAMAP-Rule:MF_01210}; DE AltName: Full=Carbamoyl phosphate synthetase ammonia chain {ECO:0000256|HAMAP-Rule:MF_01210}; GN Name=carB {ECO:0000256|HAMAP-Rule:MF_01210}; GN ORFNames=VR68_05885 {ECO:0000313|EMBL:KJS01020.1}; OS Peptococcaceae bacterium BRH_c4a. OC Bacteria; Bacillota; Clostridia; Eubacteriales; Peptococcaceae. OX NCBI_TaxID=1629716 {ECO:0000313|EMBL:KJS01020.1, ECO:0000313|Proteomes:UP000033439}; RN [1] {ECO:0000313|EMBL:KJS01020.1, ECO:0000313|Proteomes:UP000033439} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=BRH_c4a {ECO:0000313|EMBL:KJS01020.1}; RA Bagnoud A., Chourey K., Hettich R.L., de Bruijn I., Andersson A.F., RA Leupin O.X., Schwyn B., Bernier-Latmani R.; RT "Microbial metabolic network in the subsurface."; RL Submitted (MAR-2015) to the EMBL/GenBank/DDBJ databases. 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:0000256|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:0000256|HAMAP- CC Rule:MF_01210}; CC -!- CATALYTIC ACTIVITY: 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; CC Evidence={ECO:0000256|ARBA:ARBA00043687, ECO:0000256|HAMAP- CC Rule:MF_01210}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000256|HAMAP-Rule:MF_01210}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|HAMAP-Rule:MF_01210}; CC Note=Binds 4 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000256|HAMAP- CC Rule:MF_01210}; CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; carbamoyl CC phosphate from bicarbonate: step 1/1. {ECO:0000256|HAMAP- CC Rule:MF_01210}. CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; CC (S)-dihydroorotate from bicarbonate: step 1/3. {ECO:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_01210}. CC -!- SIMILARITY: Belongs to the CarB family. {ECO:0000256|ARBA:ARBA00009799, CC ECO:0000256|HAMAP-Rule:MF_01210}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_01210}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:KJS01020.1}. 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; LADN01000039; KJS01020.1; -; Genomic_DNA. DR AlphaFoldDB; A0A0F2NIS3; -. DR STRING; 1629716.VR68_05885; -. DR PATRIC; fig|1629716.3.peg.156; -. DR UniPathway; UPA00068; UER00171. DR UniPathway; UPA00070; UER00115. DR Proteomes; UP000033439; Unassembled WGS sequence. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0004070; F:aspartate carbamoyltransferase activity; IEA:TreeGrafter. 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:0004151; F:dihydroorotase activity; IEA:TreeGrafter. DR GO; GO:0046872; F:metal ion binding; IEA:InterPro. DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IEA:TreeGrafter. 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 GO; GO:0019240; P:citrulline biosynthetic process; IEA:TreeGrafter. DR GO; GO:0006541; P:glutamine metabolic process; IEA:TreeGrafter. DR GO; GO:0006228; P:UTP biosynthetic process; IEA:TreeGrafter. DR Gene3D; 3.40.50.20; -; 2. 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; 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; 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; 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 {ECO:0000256|HAMAP-Rule:MF_01210}; KW Arginine biosynthesis {ECO:0000256|ARBA:ARBA00022571, ECO:0000256|HAMAP- KW Rule:MF_01210}; KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|HAMAP- KW Rule:MF_01210}; KW Ligase {ECO:0000256|ARBA:ARBA00022598, ECO:0000256|HAMAP-Rule:MF_01210}; KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|HAMAP- KW Rule:MF_01210}; KW Pyrimidine biosynthesis {ECO:0000256|ARBA:ARBA00022975, ECO:0000256|HAMAP- KW Rule:MF_01210}; KW Repeat {ECO:0000256|ARBA:ARBA00022737, ECO:0000256|HAMAP-Rule:MF_01210}. FT DOMAIN 133..327 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 673..863 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 932..1076 FT /note="MGS-like" FT /evidence="ECO:0000259|PROSITE:PS51855" FT REGION 1..401 FT /note="Carboxyphosphate synthetic domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT REGION 549..931 FT /note="Carbamoyl phosphate synthetic domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT REGION 932..1076 FT /note="Allosteric domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 129 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 169 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 175 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 176 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 208 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 210 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 215 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 241 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 242 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 243 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 284 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 284 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 284 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 298 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 300 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 300 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 709 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 748 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 750 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 754 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 779 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 780 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 781 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 782 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 822 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 822 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 822 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 834 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 836 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 836 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" SQ SEQUENCE 1076 AA; 116730 MW; 93D315D8934A959D CRC64; MPRHKDIKKV LVIGSGPIVI GQAAEFDYAG TQACKALSEE GAEVALINSN PATIMTDPGI AHQVYIEPLT WQSVAGVIKR ERPDGLLPTL GGQTGLNLAV ELADRGVLKK YGVKLLGTSL EAIKKAEDRQ LFKETMLAIG EPVPDSIIAL NLDHAREFVS RVGFPVIVRP AYTLGGTGGG IVGNDAELAD IVTRGLKLSM IGQVLLERSV AGWKEIEYEV MRDGAGNCIT ICNMENIDPI GVHTGDSIVV APSQTLADRE YQMLRTASLK IIRALKVEGG CNVQFALDPY SYNYYVIEVN PRVSRSSALA SKATGYPIAK MAAKIAVGLN LDEIVNPVTG KTTACFEPAL DYVVVKIPRW PFDKFGSADR TLGTQMKATG EVMAIDRSFE GALMKAVRSL EIGVDSLKLK GSASWSEMEL EERLARPNDE RLFVMAEAFR RFWAMREVSQ LTRIDYFFLE KIKNIVVTEG ELKNRRGPVD LETLARAKTL GISDSQVARL TRTTVGEVRA LRKEYGLTPS YKVVDTCSAE FESATPYYYS TYDSQDEVEV SGRKKALVLG SGPIRIGQGI EFDYCSVHSV WGLQAENVES VIVNNNPETV STDFDTSDKL YFEPLTLEDV LNIIDKEKPD GVIVQFGGQT AINLAGELDK QGVGILGTPV ECIDAAEDRE KFGDLLRSLN IPQTEGGTAF NVRGALEIAD KVGYPVLVRP SYVLGGRAME IVHSDQELLK YMETAVQITP KHPVLVDKYV LGKEVEVDAI GDGKDIFIPG IMEHVERAGV HSGDSIAVYP PQTLSDRETA GIVEYTLRIG RALKICGLMN IQYVVGKNGI FVLEVNPRAS RTVPVLSKVT GIPMVQVATR AMLGRSLESM GYGSGLGPTP NLVTVKAPVF SFEKLGLVET SLGPEMKSTG EVMGIDRTFP LALYKAMVSS GLKIVTGGDL LVSLSDRDKE EALPIIRCYV DMGFKLYATG GTASALAGAG LAVEDAANAE TMIRSGRISL VINTPTRGKI PGRPGFMMRR AASEYRVPCL TSLDTAQALA VMLQSIGRGE EPEPVNMRDF TSFTSFTSLA YRRAAI //