ID A0A417HRR3_9FIRM Unreviewed; 1061 AA. AC A0A417HRR3; DT 08-MAY-2019, integrated into UniProtKB/TrEMBL. DT 08-MAY-2019, sequence version 1. DT 29-MAY-2024, entry version 18. 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=DW742_09955 {ECO:0000313|EMBL:RHT75240.1}; OS Butyricicoccus sp. AM28-25. OC Bacteria; Bacillota; Clostridia; Eubacteriales; Butyricicoccaceae; OC Butyricicoccus. OX NCBI_TaxID=2292294 {ECO:0000313|EMBL:RHT75240.1, ECO:0000313|Proteomes:UP000283242}; RN [1] {ECO:0000313|EMBL:RHT75240.1, ECO:0000313|Proteomes:UP000283242} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=AM28-25 {ECO:0000313|EMBL:RHT75240.1, RC ECO:0000313|Proteomes:UP000283242}; RA Zou Y., Xue W., Luo G.; RT "A genome reference for cultivated species of the human gut microbiota."; RL Submitted (AUG-2018) 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|ARBA:ARBA00005077, CC ECO:0000256|HAMAP-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:RHT75240.1}. 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; QUJL01000010; RHT75240.1; -; Genomic_DNA. DR AlphaFoldDB; A0A417HRR3; -. DR OrthoDB; 9804197at2; -. DR UniPathway; UPA00068; UER00171. DR UniPathway; UPA00070; UER00115. DR Proteomes; UP000283242; 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:UniProtKB-KW. 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 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_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; 1. DR PROSITE; PS00867; CPSASE_2; 2. DR PROSITE; PS51855; MGS; 1. PE 3: Inferred from homology; KW Amino-acid biosynthesis {ECO:0000256|ARBA:ARBA00022605, ECO:0000256|HAMAP- KW 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 Magnesium {ECO:0000256|ARBA:ARBA00022842}; KW Manganese {ECO:0000256|ARBA:ARBA00023211}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723}; 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 667..857 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 926..1061 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 926..1061 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 703 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 742 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 773 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 774 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 775 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 776 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 816 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 816 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 816 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 828 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 828 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 828 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 828 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 828 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 830 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 830 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" SQ SEQUENCE 1061 AA; 116800 MW; F732B82FB60A71F4 CRC64; MPLRKDIHKV MVLGSGPIVI GQAAEFDYAG TQACRALREE GLEVVLVNSN PATIMTDKAM ADKVYIEPMT VEAVQEIIKK EHPDSLLPNL GGQTGLNLAM ELCENGFLDK MGVKLLGANP TTIAKAEDRQ MFKDTMEKIG EPIIASKVVH SVEDAVDFTR EIGLPVIIRP AYTLGGTGGG IAYTWEQLRE IAASGIMYSR VDEILVEKCI AGWKEIEYEV MRDHKGNAIT ICNMENVDPV GVHTGDSVVV APSQTLCDKE YQMLRTSALN IITELGIEGG CNVQYALNPE SFEYAVIEVN PRVSRSSALA SKATGYPIAK VTAKIAVGYG LDEISNAVTG KTKACFEPTL DYCVVKFPRW PFDKFVYADN TLGTQMKATG EVMAIDNTFE GALMKAVRGC EIKLDSMIAP HIQKQSDAEI KKGVARTDDQ RLFHICEALR RGIMTIEEIH DITTMDVFFL HKFQNIIDME KELAAADKID SDLYIRAKKM GFLDKTIEQL SGKDISDVKR LPVYKMVDTC AAEFEAETPY YYSTYDDETE VAPPSGKKKI LVLGSGPIRI GQGIEFDYCS VHAVWALQKL GCETVIINNN PETVSTDFDT ADRLYFEPLT PEDVTGVVEA EKPDYAIVQF GGQTAINLAA HLEKLGVPIL GTPAWSIDAA EDREKFDVIL EKCGIPRPAG HTVMTEEEAV KAADELGYPV LVRPSYVLGG QGMEIAYKEA DVREFMQVIT RNKVENPVLV DKYMMGREIE VDAICDGDDI LIPGIMEHFE RAGVHSGDSI SIYPSINIEQ KHKDTLVKYT EALAKNLAVL GLVNIQFVLY NDQIYVIEVN PRSSRTVPYI SKVTGVPMVD LATRCMFGEK LKDMGCGTGL HPESDHYAVK VPVFSFQKLR DLDTQLGPEM KSTGEVLGVA KTFREALLKG LTGAGFQMKK KGAVLISVRD SDKQEAIRIG ERFEALGFDI YATSGTANVL NRHMVATNSI RNVDEPSPNI IDLIESGKID YVVATSVKGR HPELGSVHIR RTAVERAIPC LTSMDTVSAL LRCLEGDVKI ENCEMVDINT I //