ID A0A1Z4VRH6_9GAMM Unreviewed; 1075 AA.
AC A0A1Z4VRH6;
DT 27-SEP-2017, integrated into UniProtKB/TrEMBL.
DT 27-SEP-2017, sequence version 1.
DT 27-MAR-2024, entry version 27.
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=FOKN1_1697 {ECO:0000313|EMBL:BAZ94085.1};
OS Thiohalobacter thiocyanaticus.
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Thiohalobacterales;
OC Thiohalobacteraceae; Thiohalobacter.
OX NCBI_TaxID=585455 {ECO:0000313|EMBL:BAZ94085.1, ECO:0000313|Proteomes:UP000218765};
RN [1] {ECO:0000313|EMBL:BAZ94085.1, ECO:0000313|Proteomes:UP000218765}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FOKN1 {ECO:0000313|EMBL:BAZ94085.1,
RC ECO:0000313|Proteomes:UP000218765};
RA Oshiki M., Fukushima T., Kawano S., Nakagawa J.;
RT "Thiocyanate degradation by Thiohalobacter thiocyanaticus FOKN1.";
RL Submitted (MAY-2017) 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 ---------------------------------------------------------------------------
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; AP018052; BAZ94085.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1Z4VRH6; -.
DR KEGG; ttc:FOKN1_1697; -.
DR OrthoDB; 9804197at2; -.
DR UniPathway; UPA00068; UER00171.
DR UniPathway; UPA00070; UER00115.
DR Proteomes; UP000218765; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
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 CDD; cd01424; MGS_CPS_II; 1.
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; 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}; Reference proteome {ECO:0000313|Proteomes:UP000218765};
KW Repeat {ECO:0000256|ARBA:ARBA00022737, ECO:0000256|HAMAP-Rule:MF_01210}.
FT DOMAIN 133..328
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 678..869
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 936..1074
FT /note="MGS-like"
FT /evidence="ECO:0000259|PROSITE:PS51855"
FT REGION 1..403
FT /note="Carboxyphosphate synthetic domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT REGION 404..553
FT /note="Oligomerization domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT REGION 936..1075
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 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 285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 285
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 285
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 299
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 299
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 299
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 299
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 301
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 301
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 714
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 753
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 755
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 760
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 785
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 786
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 787
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 788
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="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="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 840
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 840
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 840
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 840
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 840
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 842
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 842
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
SQ SEQUENCE 1075 AA; 118651 MW; 440970D94A87C6B9 CRC64;
MPKRTDIESI LILGAGPIVI GQACEFDYSG AQACKALREE GYRVILVNSN PATIMTDPEM
SGATYIEAVD WRTVEKIIEK ERPDALLPTM GGQTALNCAL DLDREGILEK YGVEMIGASK
DAIDKAEDRD RFRQAMRRIG LDFPTSEMAH SMEEAMQVQE KIGFPTIIRP SFTLGGSGGG
IAYNKEEFIE ICERGLDLSP TNELLIEESA LGWKEYEMEV VRDRKDNCII VCSIENLDPM
GIHTGDSITV APAQTLTDKE YQIMRDASLA VLREIGVETG GSNVQFAINP DNGRMIIIEM
NPRVSRSSAL ASKATGFPIA KVAAKLAVGY TLDELQNEIT GGATPASFEP SIDYVVTKIP
RFTFEKFSQA QAYLTTQMKS VGEVMAIGRN FQESFQKALR GLETGIDGLS EKLDLAHEDT
KDRLRSELKQ PGPERILYLG DAFRFGMSLD EVHEYTAIDP WFLEQIEEII QLEAMVQDKG
IDGLDRDTLW RLKRKGFADS RLAHLARVKE SAVRELRHQH GLRPAFKRVD TCAAEFATGT
AYMYSTYEEE CEAEPTDRKK IMVLGGGPNR IGQGIEFDYC CVHAAFAMRE DGYETIMVNC
NPETVSTDYD TSDRLYFEPL TLEDVLEIIE KEQPEGVIVQ YGGQTPLKLA RDLEAAGAPI
IGTSPDSIDL AEDRERFQDM INRLGLKQPP NRTARTEEEA LRLAAEIGYP LVVRPSYVLG
GRAMEIVYQE EDLARYMNDA VKVSNDSPVL LDRFLDDAVE VDVDAICDGK DVLIGGIMEH
IEQAGVHSGD SACSLPPYTL SLEAQERMRE QVAAMARELK VIGLMNTQFA IKGEEIYIIE
VNPRASRTVP YVSKVTGRPL AKIAARCMAG RSLADQDALV ETVPTYFSVK EAVFPFIKFP
GVDPILGPEM KSTGEVMGVG RTFGAAFGRA QLGAGVVLPR SGKIFISVRD TDKPDVVALA
RGFADKGFSL VATRGTAREI TAAGINCEIV NKVIEGRPHI VDMIKNDQIS YVVNTTEGKQ
AIADSFTIRR TALHHKVHVS TTMAHAEAIV MALDAIDNAE VNRLQDLHRE LGMIE
//
