ID A0A365P8H2_9ACTN Unreviewed; 1120 AA. AC A0A365P8H2; DT 07-NOV-2018, integrated into UniProtKB/TrEMBL. DT 07-NOV-2018, sequence version 1. DT 29-MAY-2024, entry version 22. 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 ECO:0000313|EMBL:RBA33540.1}; GN ORFNames=DQ226_12505 {ECO:0000313|EMBL:RBA33540.1}; OS Dietzia maris. OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Dietziaceae; OC Dietzia. OX NCBI_TaxID=37915 {ECO:0000313|EMBL:RBA33540.1, ECO:0000313|Proteomes:UP000252187}; RN [1] {ECO:0000313|EMBL:RBA33540.1, ECO:0000313|Proteomes:UP000252187} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=SST1 {ECO:0000313|EMBL:RBA33540.1, RC ECO:0000313|Proteomes:UP000252187}; RA Abdel-Mageed W.M., Lehri B., Jarmusch S.A., Miranda K., Goodfellow M., RA Jaspars M., Karlyshev A.V.; RT "Whole genome sequencing of four bacterial strains from South Shetland RT trench revealing bio-synthetic gene clusters."; RL Submitted (JUN-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:RBA33540.1}. 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; QNTT01000035; RBA33540.1; -; Genomic_DNA. DR RefSeq; WP_067717954.1; NZ_JAUHTB010000001.1. DR AlphaFoldDB; A0A365P8H2; -. DR GeneID; 84686736; -. DR UniPathway; UPA00068; UER00171. DR UniPathway; UPA00070; UER00115. DR Proteomes; UP000252187; 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; 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. DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 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 138..333 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 695..886 FT /note="ATP-grasp" FT /evidence="ECO:0000259|PROSITE:PS50975" FT DOMAIN 968..1120 FT /note="MGS-like" FT /evidence="ECO:0000259|PROSITE:PS51855" FT REGION 1..407 FT /note="Carboxyphosphate synthetic domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT REGION 968..1120 FT /note="Allosteric domain" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 134 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 180 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 181 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 215 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 220 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 246 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 247 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 248 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 290 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 290 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 290 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 304 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 304 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 304 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 304 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 304 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 306 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 306 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 731 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 772 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 777 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 802 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 803 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 804 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 805 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 845 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 845 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 845 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 857 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 857 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 857 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 857 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 857 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 859 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" FT BINDING 859 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210" SQ SEQUENCE 1120 AA; 119260 MW; AAFD841F9C540401 CRC64; MPRRTDINHV LVIGSGPIVI GQACEFDYSG TQACRVLKSE GLRVTLVNSN PATIMTDPEF ADATYVEPIT PEFIDKILTK EAADGHPVDA VLATLGGQTA LNAAMQLDAQ GLLDKHGVEL IGADIPAINR GEDRQTFKDI VASVGGESAR SAVCHTMEEV HATVAELGLP VVVRPSFTMG GLGSGLAYTT EDLERIAGGG LSASPTANVL IEESILGWKE YELELMRDNK DNVVVICSIE NVDALGVHTG DSVTVAPSMT LTDREFQNMR DLGIAIIRAV GVDTGGCNIQ FAINPVDGRL VVIEMNPRVS RSSALASKAT GFPIAKIAAR LAIGYSLDEI TNDITGETPA CFEPTLDYVV VKAPRFAFEK FPGADDTLTT TMKSVGEAMS LGRNYREALG KVMRSLETKA SGFWTLPDET IAPGRSTDVD AVLADLVRPT EGRMYDVELA LRLGATVQQV HEASGIDPWF LEEVAELVDL RREIVDAAVL GADLLRRAKH NGLSDAQIAA LRPEFAGAEG VQRLRHRLGI RPVYKTVDTC AAEFEAKTPY HYSTYELDPA AESEVAPQTE REKVIILGSG PNRIGQGIEF DYSCVHAALT LSEAGYETVM VNCNPETVST DYDTADRLYF EPLTFEDVME VYHAESESGT VAGVLVQLGG QTPLGLAAQL EAAGVPIVGT SPSAIDLAED RREFGEVLVR AGLPAPAFGT AINADEATAI AADIGYPVLV RPSYVLGGRG MEIVYDEGSL RSYIDRATEI SPDRPVLVDR FLDDAVEIDV DVLCDGTEVY LGGVMEHIEE AGIHSGDSAC TLPPITLGQD DIDRVRRSSE ALAMGIGVKG LMNVQYALKD DVLYVLEANP RASRTVPFVS KATGVHLAKA CARIMLGESI ADLRAEGLLP SDRDGGSLPA DAPVAVKEAV LPFNRFRTPE GDTVESLLSP EMKSTGEVMG IGPDFAVAFA KGQLSADGVL PLSGTVFVSV ANRDKRSMVF PAQRLAALGF TVLATEGTAL MLRRYGIACE TVAKLTESGT GPVDEDGRPI RTIVDRINAD EVDLILNIAS STGGTRADGH EIRSAAISRR VPCVTTVQGA TAAVHGIEAM LRGDVSVSPL QELHAGYAAR //