ID PYR1_CAEEL Reviewed; 2198 AA. AC Q18990; DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 2. DT 27-MAR-2024, entry version 174. DE RecName: Full=Multifunctional protein pyr-1 {ECO:0000305}; DE Includes: DE RecName: Full=Glutamine-dependent carbamoyl-phosphate synthase {ECO:0000250|UniProtKB:P27708}; DE EC=6.3.5.5 {ECO:0000250|UniProtKB:P27708}; DE Includes: DE RecName: Full=Glutamine amidotransferase; DE Short=GATase; DE Short=GLNase; DE EC=3.5.1.2 {ECO:0000250|UniProtKB:P07259}; DE Includes: DE RecName: Full=Ammonium-dependent carbamoyl phosphate synthase; DE Short=CPS; DE Short=CPSase; DE EC=6.3.4.16 {ECO:0000250|UniProtKB:P07259}; DE Includes: DE RecName: Full=Aspartate carbamoyltransferase {ECO:0000250|UniProtKB:P27708}; DE EC=2.1.3.2 {ECO:0000250|UniProtKB:P27708}; DE Includes: DE RecName: Full=Dihydroorotase {ECO:0000250|UniProtKB:P27708}; DE EC=3.5.2.3 {ECO:0000250|UniProtKB:P27708}; GN Name=pyr-1 {ECO:0000303|PubMed:16828468, GN ECO:0000312|WormBase:D2085.1}; GN ORFNames=D2085.1 {ECO:0000312|WormBase:D2085.1}; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940}; RN [1] {ECO:0000312|Proteomes:UP000001940} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940}; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for investigating RT biology."; RL Science 282:2012-2018(1998). RN [2] {ECO:0000305} RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, RP AND MUTAGENESIS OF HIS-1602. RX PubMed=16828468; DOI=10.1016/j.ydbio.2006.06.008; RA Franks D.M., Izumikawa T., Kitagawa H., Sugahara K., Okkema P.G.; RT "C. elegans pharyngeal morphogenesis requires both de novo synthesis of RT pyrimidines and synthesis of heparan sulfate proteoglycans."; RL Dev. Biol. 296:409-420(2006). RN [3] {ECO:0000305} RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-1602. RX PubMed=20148972; DOI=10.1111/j.1742-4658.2010.07573.x; RA Levitte S., Salesky R., King B., Coe Smith S., Depper M., Cole M., RA Hermann G.J.; RT "A Caenorhabditis elegans model of orotic aciduria reveals enlarged RT lysosome-related organelles in embryos lacking umps-1 function."; RL FEBS J. 277:1420-1439(2010). RN [4] RP MUTAGENESIS OF HIS-1602. RX PubMed=30102152; DOI=10.7554/elife.36588; RA Liu Y., Zou W., Yang P., Wang L., Ma Y., Zhang H., Wang X.; RT "Autophagy-dependent ribosomal RNA degradation is essential for maintaining RT nucleotide homeostasis during C. elegans development."; RL Elife 7:0-0(2018). CC -!- FUNCTION: Multifunctional protein that encodes the first 3 enzymatic CC activities of the de novo pyrimidine pathway: carbamoylphosphate CC synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; CC EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase- CC function is accomplished in 2 steps, by a glutamine-dependent CC amidotransferase activity (GATase) that binds and cleaves glutamine to CC produce ammonia, followed by an ammonium-dependent carbamoyl phosphate CC synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to CC form carbamoyl phosphate. The endogenously produced carbamoyl phosphate CC is sequestered and channeled to the ATCase active site. ATCase then CC catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and CC carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization CC of carbamoyl aspartate to dihydroorotate (By similarity). Involved in CC the elongation of the pharyngeal isthmus during development, probably CC by providing precursors of UDP-sugars required for heparan sulfate CC proteoglycan biosynthesis (PubMed:16828468). Regulates the organization CC of the actin and intermediate filaments cytoskeleton in the pharyngeal CC muscles (PubMed:16828468). {ECO:0000250|UniProtKB:P27708, CC ECO:0000269|PubMed:16828468}. 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:P27708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+); CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; EC=3.5.1.2; CC Evidence={ECO:0000250|UniProtKB:P07259}; 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:P07259}; 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; CC Evidence={ECO:0000250|UniProtKB:P27708}; 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:0000250|UniProtKB:P27708}; 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00409}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00409}; CC Note=Binds 4 magnesium or manganese ions per subunit. CC {ECO:0000255|PROSITE-ProRule:PRU00409}; CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; CC (S)-dihydroorotate from bicarbonate: step 1/3. CC {ECO:0000250|UniProtKB:P27708}. CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; CC (S)-dihydroorotate from bicarbonate: step 2/3. CC {ECO:0000250|UniProtKB:P27708}. CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; CC (S)-dihydroorotate from bicarbonate: step 3/3. CC {ECO:0000250|UniProtKB:P27708}. CC -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:P27708}. CC -!- TISSUE SPECIFICITY: Expressed in the intestine. CC {ECO:0000269|PubMed:16828468}. CC -!- DEVELOPMENTAL STAGE: Expressed predominantly in gut precursor cells CC from the 4E embryonic stage until the bean stage. Expression resumes at CC the L1 larval stage and continues into adulthood. CC {ECO:0000269|PubMed:16828468}. CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes an arrest at the CC embryonic stage or at the L1 larval stage (PubMed:16828468). The few CC surviving animals grow more slowly (PubMed:16828468). L1 larvae have CC incomplete pharyngeal isthmus elongation, 36 percent of which have the CC pharynx detached from the buccal cavity (PubMed:16828468). In an umps-1 CC zu456 mutant background embryo, prevents the formation of abnormally CC enlarged gut granules (PubMed:20148972). {ECO:0000269|PubMed:16828468, CC ECO:0000269|PubMed:20148972}. 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). {ECO:0000250|UniProtKB:P07259}. CC -!- SIMILARITY: In the N-terminal section; belongs to the CarA family. CC {ECO:0000305}. CC -!- SIMILARITY: In the 2nd section; belongs to the CarB family. CC {ECO:0000305}. CC -!- SIMILARITY: In the 3rd section; belongs to the metallo-dependent CC hydrolases superfamily. DHOase family. CAD subfamily. {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC aspartate/ornithine carbamoyltransferase superfamily. ATCase family. CC {ECO:0000305}. 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; BX284602; CAA91059.2; -; Genomic_DNA. DR RefSeq; NP_495838.2; NM_063437.4. DR AlphaFoldDB; Q18990; -. DR SMR; Q18990; -. DR STRING; 6239.D2085.1.1; -. DR EPD; Q18990; -. DR PaxDb; 6239-D2085-1; -. DR PeptideAtlas; Q18990; -. DR EnsemblMetazoa; D2085.1.1; D2085.1.1; WBGene00004259. DR GeneID; 174385; -. DR KEGG; cel:CELE_D2085.1; -. DR UCSC; D2085.1; c. elegans. DR AGR; WB:WBGene00004259; -. DR WormBase; D2085.1; CE41886; WBGene00004259; pyr-1. DR eggNOG; KOG0370; Eukaryota. DR GeneTree; ENSGT00940000157241; -. DR HOGENOM; CLU_000513_2_0_1; -. DR InParanoid; Q18990; -. DR OMA; WSPFNGK; -. DR OrthoDB; 309at2759; -. DR PhylomeDB; Q18990; -. DR Reactome; R-CEL-500753; Pyrimidine biosynthesis. DR UniPathway; UPA00070; UER00115. DR UniPathway; UPA00070; UER00116. DR UniPathway; UPA00070; UER00117. DR PRO; PR:Q18990; -. DR Proteomes; UP000001940; Chromosome II. DR Bgee; WBGene00004259; Expressed in embryo and 4 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0016597; F:amino acid binding; IEA:InterPro. DR GO; GO:0004070; F:aspartate carbamoyltransferase activity; IBA:GO_Central. 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:0004151; F:dihydroorotase activity; IBA:GO_Central. DR GO; GO:0004359; F:glutaminase activity; IEA:RHEA. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IBA:GO_Central. DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0019240; P:citrulline biosynthetic process; IBA:GO_Central. DR GO; GO:0006541; P:glutamine metabolic process; IBA:GO_Central. DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB. DR GO; GO:1905905; P:nematode pharyngeal gland morphogenesis; IMP:UniProtKB. DR GO; GO:0160094; P:nematode pharynx development; IMP:UniProtKB. DR GO; GO:0060465; P:pharynx development; IMP:WormBase. DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IMP:WormBase. DR GO; GO:0006228; P:UTP biosynthetic process; IBA:GO_Central. DR CDD; cd01316; CAD_DHOase; 1. DR CDD; cd01744; GATase1_CPSase; 1. DR CDD; cd01423; MGS_CPS_I_III; 1. DR Gene3D; 3.40.50.20; -; 2. DR Gene3D; 3.40.50.880; -; 1. DR Gene3D; 3.40.50.1370; Aspartate/ornithine carbamoyltransferase; 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; 3.50.30.20; Carbamoyl-phosphate synthase small subunit, N-terminal domain; 1. DR Gene3D; 1.10.1030.10; Carbamoyl-phosphate synthetase, large subunit oligomerisation domain; 1. DR Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1. DR Gene3D; 3.40.50.1380; Methylglyoxal synthase-like domain; 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 NCBIfam; TIGR00670; asp_carb_tr; 1. DR NCBIfam; TIGR01369; CPSaseII_lrg; 1. DR NCBIfam; TIGR01368; CPSaseIIsmall; 1. DR PANTHER; PTHR11405:SF5; CAD PROTEIN; 1. DR PANTHER; PTHR11405; CARBAMOYLTRANSFERASE FAMILY MEMBER; 1. 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; PR00101; ATCASE. DR PRINTS; PR00098; CPSASE. DR PRINTS; PR00099; CPSGATASE. DR SMART; SM01096; CPSase_L_D3; 1. DR SMART; SM01097; CPSase_sm_chain; 1. DR SMART; SM00851; MGS; 1. DR SUPFAM; SSF53671; Aspartate/ornithine carbamoyltransferase; 1. DR SUPFAM; SSF48108; Carbamoyl phosphate synthetase, large subunit connection domain; 1. DR SUPFAM; SSF52021; Carbamoyl phosphate synthetase, small subunit N-terminal domain; 1. DR SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1. DR SUPFAM; SSF51338; Composite domain of metallo-dependent hydrolases; 1. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 2. DR SUPFAM; SSF51556; Metallo-dependent hydrolases; 1. DR SUPFAM; SSF52335; Methylglyoxal synthase-like; 1. DR SUPFAM; SSF52440; PreATP-grasp domain; 2. 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 ATP-binding; Glutamine amidotransferase; Hydrolase; Ligase; Magnesium; KW Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding; KW Pyrimidine biosynthesis; Reference proteome; Repeat; Transferase; Zinc. FT CHAIN 1..2198 FT /note="Multifunctional protein pyr-1" FT /evidence="ECO:0000305" FT /id="PRO_0000438771" FT DOMAIN 180..366 FT /note="Glutamine amidotransferase type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605" FT DOMAIN 516..708 FT /note="ATP-grasp 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT DOMAIN 1054..1245 FT /note="ATP-grasp 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT DOMAIN 1318..1474 FT /note="MGS-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01202" FT REGION 3..368 FT /note="GATase (Glutamine amidotransferase)" FT /evidence="ECO:0000250|UniProtKB:P08955" FT REGION 392..1467 FT /note="CPSase (Carbamoyl-phosphate synthase)" FT /evidence="ECO:0000250|UniProtKB:P08955" FT REGION 392..934 FT /note="CPSase A" FT /evidence="ECO:0000250|UniProtKB:P08955" FT REGION 935..1467 FT /note="CPSase B" FT /evidence="ECO:0000250|UniProtKB:P08955" FT REGION 1468..1799 FT /note="DHOase (dihydroorotase)" FT /evidence="ECO:0000250|UniProtKB:P08955" FT REGION 1800..1870 FT /note="Linker" FT /evidence="ECO:0000250|UniProtKB:P08955" FT REGION 1871..2196 FT /note="ATCase (Aspartate transcarbamylase)" FT /evidence="ECO:0000250|UniProtKB:P08955" FT ACT_SITE 255 FT /note="Nucleophile; for GATase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605" FT ACT_SITE 339 FT /note="For GATase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605" FT ACT_SITE 341 FT /note="For GATase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00605" FT ACT_SITE 1695 FT /note="For DHOase activity" FT /evidence="ECO:0000250|UniProtKB:P05020" FT BINDING 45 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 226 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 228 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 256 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 259 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 297 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 299 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 300 FT /ligand="L-glutamine" FT /ligand_id="ChEBI:CHEBI:58359" FT /evidence="ECO:0000250|UniProtKB:P0A6F1" FT BINDING 512 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 552 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 558 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 559 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 589 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 596 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 622 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 623 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 624 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 665 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 665 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 665 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 679 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 679 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 679 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 679 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 679 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 681 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 681 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1090 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1129 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1131 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1136 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1161 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1162 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1163 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1164 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1204 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1204 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1204 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1216 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P00968" FT BINDING 1216 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="3" 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 1216 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1216 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1218 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1218 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 1483 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1483 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1485 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1487 FT /ligand="(S)-dihydroorotate" FT /ligand_id="ChEBI:CHEBI:30864" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1517 FT /ligand="(S)-dihydroorotate" FT /ligand_id="ChEBI:CHEBI:30864" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1568 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 1568 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 1602 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1626 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1649 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1670 FT /ligand="(S)-dihydroorotate" FT /ligand_id="ChEBI:CHEBI:30864" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1695 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1699 FT /ligand="(S)-dihydroorotate" FT /ligand_id="ChEBI:CHEBI:30864" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1713 FT /ligand="(S)-dihydroorotate" FT /ligand_id="ChEBI:CHEBI:30864" FT /evidence="ECO:0000250|UniProtKB:P27708" FT BINDING 1929 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 1930 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 1957 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 1978 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 2006 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 2009 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 2039 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 2103 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 2156 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT BINDING 2157 FT /ligand="carbamoyl phosphate" FT /ligand_id="ChEBI:CHEBI:58228" FT /evidence="ECO:0000250|UniProtKB:P0A786" FT MOD_RES 1568 FT /note="N6-carboxylysine" FT /evidence="ECO:0000250|UniProtKB:P27708" FT MUTAGEN 1602 FT /note="H->Q: In cu8; probable loss of dihydroorotase FT activity. Severe late stage embryonic lethality in 50% of FT animals. The few surviving mutants have a shorter and FT thicker pharyngeal isthmus, an abnormal knobbed tail, mild FT egg-laying defects, moderate fluid accumulation in the FT coelom and a slower growth. Actin and intermediate FT filaments are disorganized in the pharynx. Moderate FT reduction in heparan sulfate levels and increased levels of FT chondroitin sulfate. In an umps-1 zu456 mutant background, FT prevents the formation of abnormally enlarged gut granules FT in embryos. Complete embryonic lethality in a rnst-2 qx245 FT mutant background." FT /evidence="ECO:0000269|PubMed:16828468, FT ECO:0000269|PubMed:20148972, ECO:0000269|PubMed:30102152" SQ SEQUENCE 2198 AA; 242582 MW; 31CFC62E64D21B1E CRC64; MRATLHLEDG STFVGSIYGA TKSVVGEIVF QTGMVGYVES LTDPSYAKQL LTLTYPLIGN YGVPSAEILD QFKLPAEFES DRIWPAALIV EKICVDGEHS HWQAVQSLSE WLRKADVPCL SGIDVRQLVK KIRETGTMKA KLVIESDNAQ NFDYVDVNAE NLVDFVSRKE PVVYGSGDQT ILAVDCGLKN NQIRCLAKRG FRVKVVPWNH PIDTESDYDG LFLSNGPGDP EICAPLVDRL AKVIARGDKP IFGICLGHQI LSRAIGAKTY KLKYGNRGHN QPCTHYATGR CYITSQNHGY AVDPDSLPAD WKALFTNEND KTNEGIVHSS KPFFSVQFHP EHTAGPTDCE FLFDVFADSV RQAKSGTFMN VDQELTRLMT FTPIYHAKEQ RKVLVLGSGG LTIGQAGEFD YSGAQALKAL REEGIRTVLI NPNIATVQTS KGFADFTYFL PITKEYVTDV IKKERPTGIL CTFGGQTALN CAIDLYKDGI FEQYDVQVLG TQINTIMKTE DRDLFNQEIS AIGEKVAPSK AATTMEGAIE AAEELGYPVL VRAAYALGGL GSGFADNREE LIAIAQQALA HSNQVLVDKS LKGWKEVEYE VVRDAYDNCI TVCNMENVDP LGIHTGESVV VAPSQTLSDR EYNALRTCAI KVIRHLGIIG ECNIQYALDP YSLTYYIIEV NARLSRSSAL ASKATGYPLA YVAAKLALGQ HLPVIRNSVT GTTTACFEPS LDYCVVKIPR WDLGKFARVS TQIGSSMKSV GEVMGIGRCF EEALQKALRM VSDHADGFSP YTFSRPTTAD DLSKPTDKRM FALARGMYYG DFDVEKAHEL TRIDRWFLFR MQNIVDIYHR LEKTDVNTVS AELLLEAKQA GFSDRQIAKK IGSNEYTVRE ARFVKGITPC VKQIDTVAGE WPAQTNYLYT TFNGIENDVS FNMKNAVMVL GSGVYRIGSS VEFDSSCVGC IRELKALGYS TITVNCNPET VSTDYDICDR LYFEEISFET VLDVYHLEKP KGVILAFGGQ APNNIAMSLS RAQVKIFGTS PNDIDNAEDR FKFSRKLESL KISQPQWKKS ENMEDAKNFC AQVGYPCLIR PSYVLSGAAM NVAHNAEDLE VFLKQAAVVA KEHPVVVSKF INEAKELDVD AVALDGKLVV MAVSEHIENA GVHSGDATLV TPAQDMNKLT LDRIKDITFR IAEAFNVNGP FNMQLIAKNN ELKVIECNLR VSRSFPFVSK TLDYDFVALA TRAMMASDSP AIRATIKPTA TLLKGKGRVG VKVPQFSFSR LAGADVMLGV EMASTGEVAC FGTSRCDAYL KALLSTGFVV PKQNIFISIG GYHAKAEMLK SVEALLKLGY ELYGSKGTAD YFQSNKINVK PVDWPFEEGS SDEKTASGTR SVVEFLENKE FHLVINLPIR GSGAYRVSAF RTHGYKTRRM AIDNGIPLIT DIKCAKTFIQ ALEMVGKRPT MNSLVDCVTS KSLKRLPGMV DIHVHVREPG ATHKEDWATC SKAALAGGVT TILAMPNTSP VLVDTDSFYQ TEQLASAKSV VDYALYIGAT PNNSKFAAEF ADKAAGLKMY LNETFSTLKM DNISDWAKHL SAFPANRPIV CHAEKQTLAA ILCMAQMANR AVHIAHVATA DEINLVKEAK QRGWNVTCEV CPHHLFLIEE DLPDGIREVR PRLVKPEDRQ ALWDNMEYID CFATDHAPHT WAEKTGKDGK IPPGFPGVEY MLPLLLTAVH DGKLTMKELT DRMSTNPRRI FNLPPQDDTY IEVDLNEEWT IPENGGQSKA GWTPFAGRKV FGKVHNVIIR GEEAVIDGRI VAIPGFGKNV RLYPHSGTAH RGDSDFDQIL EPIPQQMIES SSDEQSPLHT PPRAHTPIAF PGELLAKNCI SVKHLDKGQI NRIFELADRY KHDVEKGHPL THILNGKVLV NLFYEVSTRT SCSFSAAMQR LGGSVISVDS QSSSVQKGET LEDTVQVLGS YGDILVLRSN ENGAADRAAR VCDQPVINGG DGTGEHPTQA LLDVYTIRQE MGTVNGLTIA LVGDLKNGRT VHSLAKLLCL YKDITLHYVA PSTELEMPQE VLDYVSSKSN FVQKKFTSLA EGINHVDVVY VTRIQKERFS SPDEYNKVKG SYVINAKLLN EAARDVEEPS SLLVPARSLP IVMHPLPRVD EIAVELDHDE RAAYFRQAKN GVFVRMSILS LLLGRGHL //