ID CARB2_AQUAE Reviewed; 537 AA.
AC O67233;
DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 27-MAR-2024, entry version 147.
DE RecName: Full=Carbamoyl phosphate synthase large chain, C-terminal section {ECO:0000305};
DE EC=6.3.4.16 {ECO:0000250|UniProtKB:P00968};
DE EC=6.3.5.5 {ECO:0000250|UniProtKB:P00968};
DE AltName: Full=Carbamoyl phosphate synthetase ammonia chain;
GN Name=carB2; OrderedLocusNames=aq_1172;
OS Aquifex aeolicus (strain VF5).
OC Bacteria; Aquificota; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX NCBI_TaxID=224324;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VF5;
RX PubMed=9537320; DOI=10.1038/32831;
RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL Nature 392:353-358(1998).
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:0000250|UniProtKB:P00968}.
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;
CC Evidence={ECO:0000250|UniProtKB:P00968};
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:0000250|UniProtKB:P00968};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P00968};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P00968};
CC Note=Binds 2 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000305};
CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; carbamoyl
CC phosphate from bicarbonate: step 1/1. {ECO:0000250|UniProtKB:P00968}.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 1/3.
CC {ECO:0000250|UniProtKB:P00968}.
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:0000250|UniProtKB:P00968}.
CC -!- DOMAIN: Corresponds to the C-terminal section. {ECO:0000305}.
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:0000250|UniProtKB:P00968}.
CC -!- SIMILARITY: Belongs to the CarB family. {ECO:0000305}.
CC -!- CAUTION: CarB is split into two genes in A.aeolicus (AQ_1172 and
CC AQ_2101). {ECO:0000305}.
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DR EMBL; AE000657; AAC07203.1; -; Genomic_DNA.
DR PIR; F70400; F70400.
DR RefSeq; NP_213797.1; NC_000918.1.
DR RefSeq; WP_010880735.1; NC_000918.1.
DR AlphaFoldDB; O67233; -.
DR SMR; O67233; -.
DR STRING; 224324.aq_1172; -.
DR EnsemblBacteria; AAC07203; AAC07203; aq_1172.
DR KEGG; aae:aq_1172; -.
DR PATRIC; fig|224324.8.peg.911; -.
DR eggNOG; COG0458; Bacteria.
DR HOGENOM; CLU_000513_3_4_0; -.
DR InParanoid; O67233; -.
DR OrthoDB; 9804197at2; -.
DR UniPathway; UPA00068; UER00171.
DR UniPathway; UPA00070; UER00115.
DR Proteomes; UP000000798; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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-EC.
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-UniPathway.
DR CDD; cd01424; MGS_CPS_II; 1.
DR Gene3D; 3.40.50.20; -; 1.
DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR Gene3D; 3.40.50.1380; Methylglyoxal synthase-like domain; 1.
DR InterPro; IPR011761; ATP-grasp.
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 PANTHER; PTHR11405:SF5; CAD PROTEIN; 1.
DR PANTHER; PTHR11405; CARBAMOYLTRANSFERASE FAMILY MEMBER; 1.
DR Pfam; PF02786; CPSase_L_D2; 1.
DR Pfam; PF02142; MGS; 1.
DR PRINTS; PR00098; CPSASE.
DR SMART; SM00851; MGS; 1.
DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR SUPFAM; SSF52335; Methylglyoxal synthase-like; 1.
DR SUPFAM; SSF52440; PreATP-grasp domain; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS00866; CPSASE_1; 1.
DR PROSITE; PS00867; CPSASE_2; 1.
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.
FT CHAIN 1..537
FT /note="Carbamoyl phosphate synthase large chain, C-terminal
FT section"
FT /id="PRO_0000144985"
FT DOMAIN 122..313
FT /note="ATP-grasp"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT DOMAIN 396..537
FT /note="MGS-like"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT REGION 1..395
FT /note="Carbamoyl phosphate synthetic domain"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT REGION 396..537
FT /note="Allosteric domain"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 197
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 272
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 272
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 272
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00968"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 284
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 284
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 286
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 286
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
SQ SEQUENCE 537 AA; 60037 MW; 9C777FD2ED8085F6 CRC64;
MSKKVVILGS GPNRIGQGIE FDYACVHAVF SLQEEGYYAV MVNCNPETVS TDYDTADKLY
FEPIVFEHVM DIIEREKPEG VILQFGGQTP LKLALPLQKN GVKILGTKPE SIDKAEDREL
FRELIIELGL KQPPSGTART KEEALKIAKE IGFPVLVRPS YVLGGRAMRI VYDEEELKEY
LEEAVSVSHE RPVLIDKFLD NSIELDVDAV SDGKDVLIGA VMEHIEEAGV HSGDSATSIP
PYSLSKEIVE EVKEQTRKLA VALEVKGLIN VQYAVQNNEV YVLEVNPRAS RTVPFVSKSI
GYPLAKIATK VAIGKSLREI LPEVFERLEK GEAHFASDFL PKEKKIFSVK EVVFPWKRFP
EVDPILGPEM KSTGEVMGID KEFGLAYYKA QLSAGYRLPE KGNLFISVAD RDKPKILELA
KEFEKLGFGI YATSGTYKFL KEHGVNAKRV LKVSEGRPNV VDMIINGEIH LVINTPSGKR
EKSDAYYIRR ACVQFNVPYY TTMRAGYAVL EAIKSIKKLK EEGKGLSVHS LQEIYNI
//
