ID F7KSP0_9FIRM Unreviewed; 1065 AA.
AC F7KSP0;
DT 21-SEP-2011, integrated into UniProtKB/TrEMBL.
DT 21-SEP-2011, sequence version 1.
DT 27-MAR-2024, entry version 70.
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=HMPREF0993_02022 {ECO:0000313|EMBL:EGN38445.1};
OS Lachnospiraceae bacterium 5_1_57FAA.
OC Bacteria; Bacillota; Clostridia; Eubacteriales; Lachnospiraceae.
OX NCBI_TaxID=658085 {ECO:0000313|EMBL:EGN38445.1, ECO:0000313|Proteomes:UP000005617};
RN [1] {ECO:0000313|EMBL:EGN38445.1, ECO:0000313|Proteomes:UP000005617}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=5_1_57FAA {ECO:0000313|EMBL:EGN38445.1,
RC ECO:0000313|Proteomes:UP000005617};
RG The Broad Institute Genome Sequencing Platform;
RA Earl A., Ward D., Feldgarden M., Gevers D., Daigneault M., Strauss J.,
RA Allen-Vercoe E., Young S.K., Zeng Q., Gargeya S., Fitzgerald M., Haas B.,
RA Abouelleil A., Alvarado L., Arachchi H.M., Berlin A., Brown A.,
RA Chapman S.B., Chen Z., Dunbar C., Freedman E., Gearin G., Gellesch M.,
RA Goldberg J., Griggs A., Gujja S., Heiman D., Howarth C., Larson L., Lui A.,
RA MacDonald P.J.P., Mehta T., Montmayeur A., Murphy C., Neiman D.,
RA Pearson M., Priest M., Roberts A., Saif S., Shea T., Shenoy N., Sisk P.,
RA Stolte C., Sykes S., Wortman J., Nusbaum C., Birren B.;
RT "The Genome Sequence of Lachnospiraceae bacterium 5_1_57FAA.";
RL Submitted (MAY-2011) 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:EGN38445.1}.
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DR EMBL; ACTR01000021; EGN38445.1; -; Genomic_DNA.
DR RefSeq; WP_009249002.1; NZ_AP024846.1.
DR AlphaFoldDB; F7KSP0; -.
DR GeneID; 69693712; -.
DR PATRIC; fig|658085.3.peg.2110; -.
DR HOGENOM; CLU_000513_1_0_9; -.
DR UniPathway; UPA00068; UER00171.
DR UniPathway; UPA00070; UER00115.
DR Proteomes; UP000005617; Unassembled WGS sequence.
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; 3.30.1490.20; 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; SM01209; GARS_A; 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; 2.
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:UP000005617};
KW Repeat {ECO:0000256|ARBA:ARBA00022737, ECO:0000256|HAMAP-Rule:MF_01210}.
FT DOMAIN 133..327
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 672..862
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 931..1065
FT /note="MGS-like"
FT /evidence="ECO:0000259|PROSITE:PS51855"
FT REGION 1..401
FT /note="Carboxyphosphate synthetic domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT REGION 931..1065
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 210
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 284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 284
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 298
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 298
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 298
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 298
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 298
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 300
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 708
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 747
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 749
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 778
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 779
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 780
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 781
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 821
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 821
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 821
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 833
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 833
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 833
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 833
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 833
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 835
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
FT BINDING 835
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01210"
SQ SEQUENCE 1065 AA; 117647 MW; E16288E64CE5C0F9 CRC64;
MPRNKEIKKV LVIGSGPIII GQAAEFDYAG TQACRSLKEE GLEVVLLNSN PATIMTDKDI
ADRVYIEPLT VEVVEQLVLK EKPDSVLPTL GGQAALNLAM ELEENGFLRR NNVRLIGTTS
ETIKKAEDRL EFKTTMEKIG EPCAASLVVE SVEEGIEFAE KIGYPVVLRP AYTLGGSGGG
IAGDRVQLVE ILENGLRLSR VGQVLVERCI AGWKEIEYEV MRDGNGNCIT VCNMENLDPV
GVHTGDSIVV APSQTLGDKE YQMLRTSALN IISELNITGG CNVQYALHPE TFEYCVIEVN
PRVSRSSALA SKATGYPIAK VAAKIALGYT LDEIRNAVTR KTYASFEPML DYCVVKIPRL
PFDKFISAKR TLSTQMKATG EVMSICDNFE GALMKAIRSL EQHVDSLMSY DFTQLTDEEL
QEELAVVDDR RIWKIAEAIR RGMGYEEIHY ITKIDKWFID KIAILVEMEQ KLQNSSLNAE
TLREAKRLEF PDSVIARLTG NTERQIHDMR LEYGITASYK MVDTCAAEFA AETPYYYSVF
GSENEAVQTS GRKKVLVLGS GPIRIGQGIE FDFCSVHCTW AFAKEGYETI IVNNNPETVS
TDFDIADKLY FEPLTPEDVE SIVDLEQPDG AVVQFGGQTA IKLTEALMKM GVPILGTSAE
NVDAAEDREL FDEILEQCQI PRPTGGTVFT AEEAKEVAGR LGYPVLVRPS YVLGGQGMQI
AINDHDIDEF IGIINRIAQD HPILVDKYLQ GKEIEVDAVC DGEDILIPGI MEHIERAGIH
SGDSISVYPA QSITEKTKRT IEDYTEKLAR SLHVIGLINI QFIVCGEDVY VIEVNPRSSR
TVPYISKVTG IPIVPLATKV IIGHKIRELG YEPGLQPEAD YFAVKMPVFS FEKIRGADIS
LGPEMKSTGE CLGIARTFDE ALYKAFLGAG IKLPKHKNMI LTVRDEDKEE AVEIGRRFER
IGYRIFATRG TAEALKSGGV KANAVNKIEQ ESPNLMDLIL GHKIDLVIDT PPQGADRSRD
GFVIRRNAIE TGVNVLTAID TAKALITSLE NTDIKKLTLI DIARI
//
