PYR1_MESAU
ID PYR1_MESAU Reviewed; 2225 AA.
AC P08955; P70108;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 4.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=CAD protein;
DE Includes:
DE RecName: Full=Glutamine-dependent carbamoyl-phosphate synthase;
DE EC=6.3.5.5 {ECO:0000269|PubMed:9218000};
DE Includes:
DE RecName: Full=Aspartate carbamoyltransferase;
DE EC=2.1.3.2 {ECO:0000269|PubMed:9218000};
DE Includes:
DE RecName: Full=Dihydroorotase;
DE EC=3.5.2.3 {ECO:0000269|PubMed:9218000};
GN Name=CAD;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-169.
RX PubMed=1671675; DOI=10.1016/s0021-9258(19)67864-6;
RA Bein K., Simmer J.P., Evans D.R.;
RT "Molecular cloning of a cDNA encoding the amino end of the mammalian
RT multifunctional protein CAD and analysis of the 5'-flanking region of the
RT CAD gene.";
RL J. Biol. Chem. 266:3791-3799(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-73.
RX PubMed=1982061;
RA Farnham P.J., Kollmar R.;
RT "Characterization of the 5' end of the growth-regulated Syrian hamster CAD
RT gene.";
RL Cell Growth Differ. 1:179-189(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 156-1455.
RX PubMed=1972379; DOI=10.1016/s0021-9258(18)86959-9;
RA Simmer J.P., Kelly R.E., Rinker A.G. Jr., Scully J.L., Evans D.R.;
RT "Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution
RT of the CPS domain of the Syrian hamster multifunctional protein CAD.";
RL J. Biol. Chem. 265:10395-10402(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 246-513.
RX PubMed=2900634; DOI=10.1016/0006-291x(88)90246-x;
RA Maley J.A., Davidson J.N.;
RT "Identification of the junction between the glutamine amidotransferase and
RT carbamyl phosphate synthetase domains of the mammalian CAD protein.";
RL Biochem. Biophys. Res. Commun. 154:1047-1053(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1391-1870.
RX PubMed=1967494; DOI=10.1073/pnas.87.1.174;
RA Simmer J.P., Kelly R.E., Rinker A.G. Jr., Zimmermann B.H., Scully J.L.,
RA Kim H., Evans D.R.;
RT "Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and
RT evolution of the dihydroorotase domain of the multifunctional protein
RT CAD.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:174-178(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1403-2110.
RX PubMed=1979549; DOI=10.1016/0378-1119(90)90399-c;
RA Williams N.K., Simpson R.J., Moritz R.L., Peide Y., Crofts L., Minasian E.,
RA Leach S.J., Wake R.G., Christopherson R.I.;
RT "Location of the dihydroorotase domain within trifunctional hamster
RT dihydroorotate synthetase.";
RL Gene 94:283-288(1990).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1774-2225.
RX PubMed=2543974; DOI=10.1073/pnas.86.12.4382;
RA Simmer J.P., Kelly R.E., Scully J.L., Grayson D.R., Rinker A.G. Jr.,
RA Bergh S.T., Evans D.R.;
RT "Mammalian aspartate transcarbamylase (ATCase): sequence of the ATCase
RT domain and interdomain linker in the CAD multifunctional polypeptide and
RT properties of the isolated domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4382-4386(1989).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2074-2225.
RX PubMed=2862577; DOI=10.1128/mcb.5.7.1735-1742.1985;
RA Shigesada K., Stark G.R., Maley J.A., Niswander L.A., Davidson J.N.;
RT "Construction of a cDNA to the hamster CAD gene and its application toward
RT defining the domain for aspartate transcarbamylase.";
RL Mol. Cell. Biol. 5:1735-1742(1985).
RN [9]
RP SUBUNIT.
RX PubMed=2995985; DOI=10.1073/pnas.82.20.6802;
RA Lee L., Kelly R.E., Pastra-Landis S.C., Evans D.R.;
RT "Oligomeric structure of the multifunctional protein CAD that initiates
RT pyrimidine biosynthesis in mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6802-6806(1985).
RN [10]
RP DOMAINS, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1348059; DOI=10.1016/s0021-9258(19)50554-3;
RA Kim H., Kelly R.E., Evans D.R.;
RT "The structural organization of the hamster multifunctional protein CAD.
RT Controlled proteolysis, domains, and linkers.";
RL J. Biol. Chem. 267:7177-7184(1992).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-1406, AND MUTAGENESIS
RP OF SER-1406.
RX PubMed=9218000; DOI=10.1007/bf02679954;
RA Banerjei L.C., Davidson J.N.;
RT "Site-directed substitution of Ser1406 of hamster CAD with glutamic acid
RT alters allosteric regulation of carbamyl phosphate synthetase II.";
RL Somat. Cell Mol. Genet. 23:37-49(1997).
RN [12]
RP 3D-STRUCTURE MODELING OF ATCASE DOMAIN.
RX PubMed=2006137; DOI=10.1002/prot.340090305;
RA Scully J.L., Evans D.R.;
RT "Comparative modeling of mammalian aspartate transcarbamylase.";
RL Proteins 9:191-206(1991).
CC -!- FUNCTION: This protein is a 'fusion' protein encoding four enzymatic
CC activities of the pyrimidine pathway (GATase, CPSase, ATCase and
CC DHOase). {ECO:0000269|PubMed:9218000}.
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:0000269|PubMed:9218000};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl phosphate + L-aspartate = H(+) + N-carbamoyl-L-
CC aspartate + phosphate; Xref=Rhea:RHEA:20013, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29991, ChEBI:CHEBI:32814, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58228; EC=2.1.3.2; Evidence={ECO:0000269|PubMed:9218000};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-dihydroorotate + H2O = H(+) + N-carbamoyl-L-aspartate;
CC Xref=Rhea:RHEA:24296, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30864, ChEBI:CHEBI:32814; EC=3.5.2.3;
CC Evidence={ECO:0000269|PubMed:9218000};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P27708};
CC Note=Binds 3 Zn(2+) ions per subunit (for dihydroorotase activity).
CC {ECO:0000250|UniProtKB:P27708};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Note=Binds 4 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409};
CC -!- ACTIVITY REGULATION: Allosterically regulated and controlled by
CC phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator
CC while UMP and UTP are inhibitors of the CPSase reaction.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 1/3.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 2/3.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC (S)-dihydroorotate from bicarbonate: step 3/3.
CC -!- SUBUNIT: Homohexamer (PubMed:2995985). Interacts with CIPC (By
CC similarity). {ECO:0000250|UniProtKB:P27708,
CC ECO:0000269|PubMed:2995985}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Note=Cytosolic
CC and unphosphorylated in resting cells, translocates to the nucleus in
CC response to EGF stimulation, nuclear import promotes optimal cell
CC growth. {ECO:0000250}.
CC -!- PTM: Activated by MAP kinase (Erk1/2) phosphorylation just prior to the
CC S phase of the cell cycle, when the demand for pyrimidine nucleotides
CC is greatest, and down-regulated as the cells emerge from S phase by
CC protein kinase A (PKA) phosphorylation. Phosphorylation at Ser-1859 by
CC RPS6KB1 downstream of MTOR promotes oligomerization and stimulates
CC dihydroorotase activity (By similarity). Phosphorylation at Ser-1406
CC reduces sensitivity to feedback inhibition by UTP. {ECO:0000250,
CC ECO:0000269|PubMed:9218000}.
CC -!- MISCELLANEOUS: GATase (glutamine amidotransferase) and CPSase
CC (carbamoyl phosphate synthase) form together the glutamine-dependent
CC CPSase (GD-CPSase) (EC 6.3.5.5).
CC -!- SIMILARITY: In the central section; belongs to the metallo-dependent
CC hydrolases superfamily. DHOase family. CAD subfamily. {ECO:0000305}.
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DR EMBL; J05503; AAA37062.1; -; mRNA.
DR EMBL; M28866; AAA37073.1; -; mRNA.
DR EMBL; M60078; AAA63617.1; -; mRNA.
DR EMBL; M11242; AAA37061.1; -; mRNA.
DR EMBL; M23652; AAA37064.1; -; mRNA.
DR EMBL; M21927; AAA37063.1; -; mRNA.
DR PIR; A38653; A23443.
DR AlphaFoldDB; P08955; -.
DR SMR; P08955; -.
DR STRING; 10036.XP_005073594.1; -.
DR MEROPS; M38.972; -.
DR iPTMnet; P08955; -.
DR eggNOG; KOG0370; Eukaryota.
DR BRENDA; 3.5.2.3; 3239.
DR SABIO-RK; P08955; -.
DR UniPathway; UPA00070; UER00115.
DR UniPathway; UPA00070; UER00116.
DR UniPathway; UPA00070; UER00117.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0016363; C:nuclear matrix; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0070335; F:aspartate binding; IDA:BHF-UCL.
DR GO; GO:0004070; F:aspartate carbamoyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; IDA:BHF-UCL.
DR GO; GO:0004151; F:dihydroorotase activity; IDA:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0002134; F:UTP binding; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006541; P:glutamine metabolic process; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
DR CDD; cd01744; GATase1_CPSase; 1.
DR Gene3D; 1.10.1030.10; -; 1.
DR Gene3D; 3.30.1490.20; -; 1.
DR Gene3D; 3.40.50.1370; -; 2.
DR Gene3D; 3.40.50.1380; -; 1.
DR Gene3D; 3.40.50.880; -; 1.
DR Gene3D; 3.50.30.20; -; 1.
DR HAMAP; MF_00001; Asp_carb_tr; 1.
DR HAMAP; MF_01209; CPSase_S_chain; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR006132; Asp/Orn_carbamoyltranf_P-bd.
DR InterPro; IPR006130; Asp/Orn_carbamoylTrfase.
DR InterPro; IPR036901; Asp/Orn_carbamoylTrfase_sf.
DR InterPro; IPR002082; Asp_carbamoyltransf.
DR InterPro; IPR006131; Asp_carbamoyltransf_Asp/Orn-bd.
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; IPR006274; CarbamoylP_synth_ssu.
DR InterPro; IPR002474; CarbamoylP_synth_ssu_N.
DR InterPro; IPR036480; CarbP_synth_ssu_N_sf.
DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR InterPro; IPR005483; CbamoylP_synth_lsu_CPSase_dom.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR035686; CPSase_GATase1.
DR InterPro; IPR002195; Dihydroorotase_CS.
DR InterPro; IPR017926; GATASE.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR InterPro; IPR011607; MGS-like_dom.
DR InterPro; IPR036914; MGS-like_dom_sf.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR Pfam; PF01979; Amidohydro_1; 1.
DR Pfam; PF02786; CPSase_L_D2; 2.
DR Pfam; PF02787; CPSase_L_D3; 1.
DR Pfam; PF00988; CPSase_sm_chain; 1.
DR Pfam; PF00117; GATase; 1.
DR Pfam; PF02142; MGS; 1.
DR Pfam; PF00185; OTCace; 1.
DR Pfam; PF02729; OTCace_N; 1.
DR PRINTS; PR00100; AOTCASE.
DR PRINTS; PR00098; CPSASE.
DR SMART; SM01096; CPSase_L_D3; 1.
DR SMART; SM01097; CPSase_sm_chain; 1.
DR SMART; SM00851; MGS; 1.
DR SUPFAM; SSF48108; SSF48108; 1.
DR SUPFAM; SSF51338; SSF51338; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
DR SUPFAM; SSF52021; SSF52021; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR SUPFAM; SSF52335; SSF52335; 1.
DR SUPFAM; SSF52440; SSF52440; 2.
DR SUPFAM; SSF53671; SSF53671; 1.
DR TIGRFAMs; TIGR00670; asp_carb_tr; 1.
DR TIGRFAMs; TIGR01369; CPSaseII_lrg; 1.
DR TIGRFAMs; TIGR01368; CPSaseIIsmall; 1.
DR PROSITE; PS50975; ATP_GRASP; 2.
DR PROSITE; PS00097; CARBAMOYLTRANSFERASE; 1.
DR PROSITE; PS00866; CPSASE_1; 2.
DR PROSITE; PS00867; CPSASE_2; 2.
DR PROSITE; PS00482; DIHYDROOROTASE_1; 1.
DR PROSITE; PS00483; DIHYDROOROTASE_2; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
DR PROSITE; PS51855; MGS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Glutamine amidotransferase; Hydrolase; Ligase;
KW Magnesium; Manganese; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Pyrimidine biosynthesis;
KW Reference proteome; Repeat; Transferase; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT CHAIN 2..2225
FT /note="CAD protein"
FT /id="PRO_0000199507"
FT DOMAIN 177..363
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT DOMAIN 519..711
FT /note="ATP-grasp 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 1052..1243
FT /note="ATP-grasp 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 1308..1462
FT /note="MGS-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01202"
FT REGION 2..365
FT /note="GATase (Glutamine amidotransferase)"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 366..394
FT /note="Linker"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 395..1455
FT /note="CPSase (Carbamoyl-phosphate synthase)"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 395..933
FT /note="CPSase A"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 934..1455
FT /note="CPSase B"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 1456..1788
FT /note="DHOase (dihydroorotase)"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 1789..1917
FT /note="Linker"
FT /evidence="ECO:0000303|PubMed:1348059"
FT REGION 1813..1911
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1918..2225
FT /note="ATCase (Aspartate transcarbamylase)"
FT /evidence="ECO:0000303|PubMed:1348059"
FT COMPBIAS 1850..1877
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 252
FT /note="Nucleophile; for GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 336
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT ACT_SITE 338
FT /note="For GATase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605"
FT BINDING 545..600
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 668
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 682
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 682
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 684
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 1078..1135
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 1202
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 1214
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 1214
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 1216
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 1471
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1471
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1473
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1475
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1505
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1556
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /note="via carbamate group"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1556
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /note="via carbamate group"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1590
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1613
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1614
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1637
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1661
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1686
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1686
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT BINDING 1690
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 456
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 747
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1038
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1406
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9218000"
FT MOD_RES 1411
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1556
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1859
FT /note="Phosphoserine; by RPS6KB1 and PKA"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1873
FT /note="Phosphoserine; by PKC; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1884
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1900
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MOD_RES 1938
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27708"
FT MUTAGEN 1406
FT /note="S->A: No effect on enzyme kinetics."
FT /evidence="ECO:0000269|PubMed:9218000"
FT MUTAGEN 1406
FT /note="S->D: Increases CPSase activity and reduces
FT sensitivity to feedback inhibition by UTP."
FT /evidence="ECO:0000269|PubMed:9218000"
SQ SEQUENCE 2225 AA; 243128 MW; 9F6EBA9BD4C6EC5A CRC64;
MAALVLEDGS VLQGRPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL VLTYPLIGNY
GIPSDEEDEF GLSKWFESSE NHVAGLVVGE CCPTPSHWSA TCTLHEWLQQ HGIPGLQGVD
TRELTKKLRE QGSLLGKLVQ SGTEPSTLPF VDPNARPLAP EVSIKTPRVF NAGGAPRICA
LDCGLKYNQI RCLCQLGAEV TVVPWNHELD SQKYDGLFLS NGPGDPASYP GVVATLNRVL
SEPNPRPVFG ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGTGRCFL TSQNHGFAVD
ADSLPAGWTP LFTNANDCSN EGIVHDSLPF FSVQFHPEHR AGPSDMELLF DVFLETVREA
VAGNPGGQTV KERLVQRLCP PGLLIPGSGL PPPRKVLILG SGGLSIGQAG EFDYSGSQAI
KALKEENIQT LLINPNIATV QTSQGLADKV YFLPITPHYV TQVIRNERPD GVLLTFGGQT
ALNCGVELTK AGVLARYGVR VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ
AQAAAERLGY PVLVRAAFAL GGLGSGFAST KEELSALVAP AFAHTSQVLI DKSLKGWKEI
EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRR TAIKVTQHLG
IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY PLAYVAAKLA LGIPLPELRN
SVTGGTAAFE PSLDYCVVKI PRWDLSKFLR VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL
RMVDENCVGF DHTVKPVSDV ELETPTDKRI FVVAAALWAG YSVERLYELT RIDCWFLHRM
KRIVTHAQLL EQHRGQPLSQ DLLHQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV
KQIDTVAAEW PAQTNYLYLT YWGNTHDLDF RTPHVLVLGS GVYRIGSSVE FDWCAVGCIQ
QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM DIYELENPDG VILSMGGQLP
NNMAMALHRQ QCRVLGTSPE AIDSAENRFK FSRLLDTIGI SQPQWRELSD LESARQFCQT
VGYPCVVRPS YVLSGAAMNV AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV
ACDGVVSAIA ISEHVENAGV HSGDATLVTP PQDITPKTLE RIKAIVHAVG QELQVTGPFN
LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR IIMGEKVEPI GLMTGSGVVG
VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL KAMLSTGFKI PKKNILLTIG
SYKNKSELLP TVRLLESLGY SLYASLGTAD FYTEHGVKVT AVDWHFEEAV DGECPPQRSI
LDQLAENHFE LVINLSMRGA GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL
GQIGPAPPLK VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGVTMV
CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGAVAG SAAGLKLYLN
ETFSELRLDS VAQWMEHFET WPSHLPIVAH AERQSVAAVL MVAQLTQRPV HICHVARKEE
ILLIKTAKAQ GLPVTCEVAP HHLFLNREDL ERLGPGRGEV RPELGSREDM EALWENMAVI
DCFASDHAPH TLEEKCGPKP PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF
HLPLQEDTYV EVDLEHEWTI PSHMPFSKAR WTPFEGQKVK GTIRRVVLRG EVAYIDGQVL
VPPGYGQDVR KWPQGAVPQP PPSAPATTEI TTTPERPRRV IPGLPDGRFH LPPRIHRASD
PGLPAEEPKE KPSRKVVEPE LMGTPDGPCY PAPPVPRQAS PQNLGSSGLL HPQTSPLLHS
LVGQHILSVK QFTKDQMSHL FNVAHTLRMM VQKERSLDIL KGKVMASMFY EVSTRTSSSF
AAAMARLGGA VLSFSEATSS VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR
PVINAGDGVG EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS
LRYVAPPSLR MPPSVWDFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE RFGSTQEYEA
CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR AAYFRQAENG MYIRMALLAT
VLGRF
