ID CARB_HELPY Reviewed; 1085 AA. AC O25577; DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 146. 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=HP_0919; OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori). OC Bacteria; Campylobacterota; Epsilonproteobacteria; Campylobacterales; OC Helicobacteraceae; Helicobacter. OX NCBI_TaxID=85962; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700392 / 26695; RX PubMed=9252185; DOI=10.1038/41483; RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G., RA Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A., RA Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N., RA Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A., RA McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E., RA Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D., RA Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S., RA Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.; RT "The complete genome sequence of the gastric pathogen Helicobacter RT pylori."; RL Nature 388:539-547(1997). 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; AE000511; AAD07963.1; -; Genomic_DNA. DR PIR; G64634; G64634. DR RefSeq; NP_207711.1; NC_000915.1. DR RefSeq; WP_001126584.1; NC_018939.1. DR AlphaFoldDB; O25577; -. DR SMR; O25577; -. DR DIP; DIP-3181N; -. DR IntAct; O25577; 6. DR MINT; O25577; -. DR STRING; 85962.HP_0919; -. DR PaxDb; 85962-C694_04730; -. DR EnsemblBacteria; AAD07963; AAD07963; HP_0919. DR KEGG; hpy:HP_0919; -. DR PATRIC; fig|85962.47.peg.984; -. DR eggNOG; COG0458; Bacteria. DR InParanoid; O25577; -. DR OrthoDB; 9804197at2; -. DR PhylomeDB; O25577; -. DR UniPathway; UPA00068; UER00171. DR UniPathway; UPA00070; UER00115. DR Proteomes; UP000000429; Chromosome. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. 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 GO; GO:0006541; P:glutamine metabolic process; IBA:GO_Central. 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; 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; 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..1085 FT /note="Carbamoyl phosphate synthase large chain" FT /id="PRO_0000145010" FT DOMAIN 131..326 FT /note="ATP-grasp 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT DOMAIN 678..871 FT /note="ATP-grasp 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT DOMAIN 952..1085 FT /note="MGS-like" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 1..399 FT /note="Carboxyphosphate synthetic domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 400..552 FT /note="Oligomerization domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 553..951 FT /note="Carbamoyl phosphate synthetic domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT REGION 952..1085 FT /note="Allosteric domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 127 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 167 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 174 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 206 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 213 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 239 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 240 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 283 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 283 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 283 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 297 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 297 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 297 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 297 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 297 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 299 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 299 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 714 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 756 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 758 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 763 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 788 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 789 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 790 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 791 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 830 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 830 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 830 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 842 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 842 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 842 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 842 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 842 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 844 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" FT BINDING 844 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01210" SQ SEQUENCE 1085 AA; 120074 MW; 696E124A50DB34C1 CRC64; MPKRTDISNI LLIGSGPIVI GQACEFDYSG TQSCKTLKSL GYRVILINSN PATVMTDPEF SHQTYIQPIT PENIATIIEK EKIDAILPTM GGQTALNAVM QMHQKGMLEG VELLGAKIEA IKKGEDRQAF KEAMLKIGMD LPKGRYAYTE LEALEAINEI GFPAIIRASF TLAGGGSGVA YNIEEFQELA KNALDASPIN EILIEESLLG WKEYEMEVIR DSKDNCIIVC CIENIDPMGV HTGDSITIAP SLTLTDKEYQ RMRDASFAIL REIGVDTGGS NVQFAIHPET LRMVVIEMNP RVSRSSALAS KATGFPIAKV ATMLAVGFSL DEIQNDITNT PASFEPSLDY IVVKIPRFAF EKFAGVSSTL GTSMKSIGEV MAIGGNFLEA LQKALCSLEN NWLGFESLSK DLEAIKKEIR RPNPKRLLYI ADAFRLGVCV DEVFELCQID RWFLSQIQKL VEVEESINSS VLTDAKKLRG LKNLGFSDAR IAAKIKENEN LEVSPFEVEL ARSNLQIVPN FEEVDTCAAE FLSLTPYLYS TYAPNPLPPI ENKQEKKEKK ILIIGSGPNR IGQGIEFDYC CVHASLALKD LNIKSVMFNC NPETVSTDYD TSDTLYFEPI HFECVKSIIQ RERVDGIIVH FGGQTPLKLA KDLAKMQAPI IGTPFKVIDI AEDREKFSLF LKELDIKQPK NGMAKSVDEA YSIANVIGFP IIVRPSYVLG GQHMQILENI EELRHYLESV THALEISPKN PLLIDKFLEK AVELDVDAIC DKKEVYIAGI LQHIEEAGIH SGDSACFIPS TLSPEILDEI ERVSAKIALH LGVVGLLNIQ FAVHQNSLYL IEVNPRASRT VPFLSKALGV PLAKVATRVM VLEDLKEALK FYDKKNIVGY SKGVYKPKMP HFVALKEAVF PFNKLYGSDL ILGPEMKSTG EVMGIARSLG LAFFKAQTAC FNPIKNKGLI FVSIKDKDKE EACVLMKRLV QLGFELCATE GTHKALEKAG VKSLKVLKIS EGRPNIMDLM MNGEISMAIN TSDHKSQDDA KLIRASVLKN HVSYFTTLST IEVLLLALEE SSKEDELLAL QDYLK //