ID E1RG39_METP4 Unreviewed; 1055 AA. AC E1RG39; DT 30-NOV-2010, integrated into UniProtKB/TrEMBL. DT 30-NOV-2010, sequence version 1. DT 04-NOV-2026, entry version 85. 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 OrderedLocusNames=Mpet_1517 {ECO:0000313|EMBL:ADN36274.1}; OS Methanolacinia petrolearia (strain DSM 11571 / OCM 486 / SEBR 4847) OS (Methanoplanus petrolearius). OC Archaea; Methanobacteriati; Methanobacteriota; Stenosarchaea group; OC Methanomicrobia; Methanomicrobiales; Methanomicrobiaceae; Methanolacinia. OX NCBI_TaxID=679926 {ECO:0000313|EMBL:ADN36274.1, ECO:0000313|Proteomes:UP000006565}; RN [1] {ECO:0000313|EMBL:ADN36274.1, ECO:0000313|Proteomes:UP000006565} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=DSM 11571 / OCM 486 / SEBR 4847 RC {ECO:0000313|Proteomes:UP000006565}; RX PubMed=21304750; RA Brambilla E., Djao O.D., Daligault H., Lapidus A., Lucas S., Hammon N., RA Nolan M., Tice H., Cheng J.F., Han C., Tapia R., Goodwin L., Pitluck S., RA Liolios K., Ivanova N., Mavromatis K., Mikhailova N., Pati A., Chen A., RA Palaniappan K., Land M., Hauser L., Chang Y.J., Jeffries C.D., Rohde M., RA Spring S., Sikorski J., Goker M., Woyke T., Bristow J., Eisen J.A., RA Markowitz V., Hugenholtz P., Kyrpides N.C., Klenk H.P.; RT "Complete genome sequence of Methanoplanus petrolearius type strain (SEBR RT 4847)."; RL Stand. Genomic Sci. 3:203-211(2010). 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|ARBA:ARBA00057223, ECO:0000256|HAMAP-Rule:MF_01210}. CC -!- CATALYTIC ACTIVITY: CC Reaction=hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl CC phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+); 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=hydrogencarbonate + NH4(+) + 2 ATP = carbamoyl phosphate + 2 CC ADP + phosphate + 2 H(+); Xref=Rhea:RHEA:18029, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:28938, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58228, ChEBI:CHEBI:456216; CC EC=6.3.4.16; Evidence={ECO:0000256|ARBA:ARBA00047359, CC ECO:0000256|HAMAP-Rule:MF_01210}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01210}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000256|HAMAP- CC Rule:MF_01210}; CC Note=Binds 4 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000256|HAMAP- CC Rule:MF_01210}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|ARBA:ARBA00001936}; 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. CC {ECO:0000256|ARBA:ARBA00004812, ECO:0000256|HAMAP-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|ARBA:ARBA00062056, CC 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 --------------------------------------------------------------------------- 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; CP002117; ADN36274.1; -; Genomic_DNA. DR RefSeq; WP_013329451.1; NC_014507.1. DR AlphaFoldDB; E1RG39; -. DR STRING; 679926.Mpet_1517; -. DR GeneID; 9743987; -. DR KEGG; mpi:Mpet_1517; -. DR eggNOG; arCOG01594; Archaea. DR HOGENOM; CLU_000513_1_0_2; -. DR OMA; AACHAIF; -. DR OrthoDB; 85487at2157; -. DR UniPathway; UPA00068; UER00171. DR UniPathway; UPA00070; UER00115. DR Proteomes; UP000006565; Chromosome. DR GO; GO:0005737; C:cytoplasm; IEA:TreeGrafter. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0004087; F:carbamoyl-phosphate synthase (ammonia) activity; IEA:UniProtKB-EC. DR GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:InterPro. DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0006526; P:L-arginine biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0006541; P:L-glutamine metabolic process; IEA:TreeGrafter. DR CDD; cd01424; MGS_CPS_II; 1. DR FunFam; 1.10.1030.10:FF:000002; Carbamoyl-phosphate synthase large chain; 1. DR FunFam; 3.30.470.20:FF:000001; Carbamoyl-phosphate synthase large chain; 1. DR FunFam; 3.30.470.20:FF:000013; Carbamoyl-phosphate synthase large chain; 1. DR FunFam; 3.40.50.20:FF:000001; Carbamoyl-phosphate synthase large chain; 2. 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; IPR036897; CarbamoylP_synth_lsu_oligo_sf. DR InterPro; IPR005479; CPAse_ATP-bd. DR InterPro; IPR005483; CPSase_dom. DR InterPro; IPR006275; CPSase_lsu. DR InterPro; IPR005480; CPSase_lsu_oligo. DR InterPro; IPR058047; CPSase_preATP-grasp. 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; NF003671; carB; 1. DR NCBIfam; TIGR01369; CPSaseII_lrg; 1. DR NCBIfam; NF009455; PRK12815.1; 1. DR PANTHER; PTHR11405:SF53; CARBAMOYL-PHOSPHATE SYNTHASE [AMMONIA], MITOCHONDRIAL; 1. DR PANTHER; PTHR11405; CARBAMOYLTRANSFERASE FAMILY MEMBER; 1. DR Pfam; PF25596; CPSase_L_D1; 2. 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; 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}; Reference proteome {ECO:0000313|Proteomes:UP000006565}; KW Repeat {ECO:0000256|ARBA:ARBA00022737, ECO:0000256|HAMAP-Rule:MF_01210}. FT DOMAIN 131..323 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 662..853 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 919..1055 FT /note="MGS-like" FT /evidence="ECO:0000259|PROSITE:PS51855" FT REGION 1..397 FT /note="Carboxyphosphate synthetic domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT REGION 921..1055 FT /note="Allosteric domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 127 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 167 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 173 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 174 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 206 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 213 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 239 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 240 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 282 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 282 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 282 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 294 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 294 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 294 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 294 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 294 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 296 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 296 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 698 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 737 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 739 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 744 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 769 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 770 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 771 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 772 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 812 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 812 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 812 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 824 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 824 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 824 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 824 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 824 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 826 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 826 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" SQ SEQUENCE 1055 AA; 116025 MW; EC5F93015CC0E6D1 CRC64; MPRREDIKKV ILIGSGPIQI GQAAEFDFSG SQACRALREE GVEVVLVNSN PATIQTDPDT ADVVYVEPLK AGIIAKIIEK EKPDGILSGM GGQTGLNLTA ELAEMGALED VEILGTPLEA IYKGEDREKF RDLMNDIGEP IPRSMILRSM DQLDNALEIV GLPAIIRPAY TLGGAGGGVA HTPEELRKIV EIGLQRSRIH QVLIEESVMG WKEIEYEVMR DSFDTCLIVC GMENVDAMGI HTGESVVVAP ILTLTDEEFH LLRTAAIKII RALDVQGGCN IQMAFKDGDY RIIEVNPRVS RSSALASKAT GYPIARVAAK IAIGLRLDEI MNSVTGCTPA SFEPSIDYVV VKIPRWPFDK FKNADRTLTT AMKSTGEVMS IGRTLEEAFM KAMRSLDTDI NSHTDKDEIR MLLQNPTDER FGCLFDAFRQ GFTVEEVSAL TFIDVFFLQK IENLVEIEKK LKSGSVSEDD IRNAVHYGFS VTEIGELTGK PEKEIEAIAG LPVYKLVDTC AAEFPAKTPY FYSTRDEGCE IDRDGKQKIL ILGSGPIRIG QGIEFDYCTV HAVMALREEG IEVHIVNNNP ETVSTDFDTS DRLFFEPMKL EDVMNILRKD DYYGVMVQFG GQNSVNLATS IEEKIKEYGL KTKILGTSPA AMDLAEDRDQ FSRLLERLDI PSPANGSAHS ETEAMQVAKK IGYPLLVRPS YVLGGRAMEL VHDDIELRNY IKEAVKVSRK HPVLLDSFLQ NAIEIDVDAV CDGEDVLIGG IMEHIEEAGV HSGDSACVIP SQSLSKNVIA TVKDYTRKLA LGIGVVGLIN IQYAVKDEVV YVLEANPRAS RTVPFVSKAT GIPLAKIAAR VMTDGKLKTY GITEKKLSHV SVKEVLLPFN KLPGVDITLS PEMKSTGEVM GIDYDFGRAY YKACISAENQ LPLEGKVFIS AGSEFKQDFV PIAKKLCSLG LSIVGTKGTV ETLRENGIEA DLVRKVQEGS PNVIDFMRRG EINLIINTPS GKYSRQDHMQ IMRAALDYNT PYITTIQAAK AAAMAIESMK KGDITIEPLS HYHEN //