ID PYR1_SQUAC Reviewed; 2242 AA. AC Q91437; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 11-JUN-2014, entry version 114. DE RecName: Full=CAD protein; DE Includes: DE RecName: Full=Glutamine-dependent carbamoyl-phosphate synthase; DE EC=6.3.5.5; DE Includes: DE RecName: Full=Aspartate carbamoyltransferase; DE EC=2.1.3.2; DE Includes: DE RecName: Full=Dihydroorotase; DE EC=3.5.2.3; GN Name=CAD; OS Squalus acanthias (Spiny dogfish). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Chondrichthyes; OC Elasmobranchii; Squalimorphii; Squaliformes; Squalidae; Squalus. OX NCBI_TaxID=7797; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Spleen, and Testis; RX PubMed=7775474; DOI=10.1074/jbc.270.23.14130; RA Hong J., Salo W.L., Anderson P.M.; RT "Nucleotide sequence and tissue-specific expression of the RT multifunctional protein carbamoyl-phosphate synthetase-aspartate RT transcarbamoylase-dihydroorotase (CAD) mRNA in Squalus acanthias."; RL J. Biol. Chem. 270:14130-14139(1995). CC -!- FUNCTION: This protein is a "fusion" protein encoding four CC enzymatic activities of the pyrimidine pathway (GATase, CPSase, CC ATCase and DHOase). CC -!- CATALYTIC ACTIVITY: 2 ATP + L-glutamine + HCO(3)(-) + H(2)O = 2 CC ADP + phosphate + L-glutamate + carbamoyl phosphate. CC -!- CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate CC + N-carbamoyl-L-aspartate. CC -!- CATALYTIC ACTIVITY: (S)-dihydroorotate + H(2)O = N-carbamoyl-L- CC aspartate. CC -!- COFACTOR: Binds 3 zinc ions per subunit (for dihydroorotase CC activity) (By similarity). CC -!- ENZYME REGULATION: Allosterically regulated and controlled by CC phosphorylation. 5-phosphoribose 1-diphosphate is an activator CC while UMP is an inhibitor of the CPSase reaction (By similarity). CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo CC pathway; (S)-dihydroorotate from bicarbonate: step 1/3. CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo CC pathway; (S)-dihydroorotate from bicarbonate: step 2/3. CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo CC pathway; (S)-dihydroorotate from bicarbonate: step 3/3. CC -!- SUBUNIT: Homohexamer. CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By CC similarity). CC -!- TISSUE SPECIFICITY: Present in the testis but not in the liver. CC -!- MISCELLANEOUS: GATase (glutamine amidotransferase) and CPSase CC (carbamoyl phosphate synthase) form together the glutamine- CC dependent CPSase (GD-CPSase) (EC 6.3.5.5). CC -!- SIMILARITY: In the central section; belongs to the DHOase family. CC -!- SIMILARITY: Contains 2 ATP-grasp domains. CC -!- SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain. 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; U18868; AAA74569.1; -; mRNA. DR PIR; A57541; A57541. DR ProteinModelPortal; Q91437; -. DR PRIDE; Q91437; -. DR HOVERGEN; HBG000279; -. DR UniPathway; UPA00070; UER00115. DR UniPathway; UPA00070; UER00116. DR UniPathway; UPA00070; UER00117. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0016597; F:amino acid binding; IEA:InterPro. DR GO; GO:0004070; F:aspartate carbamoyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; IEA:UniProtKB-EC. DR GO; GO:0004151; F:dihydroorotase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; ISS:UniProtKB. DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0070409; P:carbamoyl phosphate biosynthetic process; IEA:InterPro. DR GO; GO:0006543; P:glutamine catabolic process; IEA:InterPro. DR Gene3D; 1.10.1030.10; -; 1. DR Gene3D; 3.30.1490.20; -; 1. DR Gene3D; 3.30.470.20; -; 2. DR Gene3D; 3.40.50.1370; -; 2. DR Gene3D; 3.40.50.1380; -; 1. DR Gene3D; 3.40.50.20; -; 3. 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_1. DR InterPro; IPR006132; Asp/Orn_carbamoyltranf_P-bd. DR InterPro; IPR006130; Asp/Orn_carbamoylTrfase. 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; IPR013816; ATP_grasp_subdomain_2. DR InterPro; IPR006275; CarbamoylP_synth_lsu. DR InterPro; IPR005481; CarbamoylP_synth_lsu_N. DR InterPro; IPR005480; CarbamoylP_synth_lsu_oligo. DR InterPro; IPR006274; CarbamoylP_synth_ssu. DR InterPro; IPR002474; CarbamoylP_synth_ssu_N. 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; IPR002195; Dihydroorotase_CS. DR InterPro; IPR017926; GATASE. DR InterPro; IPR011059; Metal-dep_hydrolase_composite. DR InterPro; IPR011607; MGS-like_dom. DR InterPro; IPR016185; PreATP-grasp_dom. DR Pfam; PF01979; Amidohydro_1; 1. DR Pfam; PF00289; CPSase_L_chain; 2. 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 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; 2. 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. PE 2: Evidence at transcript level; KW Allosteric enzyme; ATP-binding; Cytoplasm; Hydrolase; Ligase; KW Metal-binding; Multifunctional enzyme; Nucleotide-binding; Nucleus; KW Phosphoprotein; Pyrimidine biosynthesis; Repeat; Transferase; Zinc. FT CHAIN 1 2242 CAD protein. FT /FTId=PRO_0000199508. FT DOMAIN 177 363 Glutamine amidotransferase type-1. FT DOMAIN 522 714 ATP-grasp 1. FT DOMAIN 1057 1248 ATP-grasp 2. FT REGION 1 365 GATase (Glutamine amidotransferase). FT REGION 366 397 Linker. FT REGION 398 1462 CPSase (Carbamoyl-phosphate synthase). FT REGION 398 937 CPSase A. FT REGION 938 1462 CPSase B. FT REGION 1463 1796 DHOase (dihydroorotase). FT REGION 1797 1934 Linker. FT REGION 1935 2242 ATCase (Aspartate transcarbamylase). FT ACT_SITE 252 252 For GATase activity (By similarity). FT ACT_SITE 336 336 For GATase activity (By similarity). FT ACT_SITE 338 338 For GATase activity (By similarity). FT METAL 1478 1478 Zinc 1; via tele nitrogen (By FT similarity). FT METAL 1478 1478 Zinc 2; via pros nitrogen (By FT similarity). FT METAL 1480 1480 Zinc 1; via tele nitrogen (By FT similarity). FT METAL 1563 1563 Zinc 1; via carbamate group (By FT similarity). FT METAL 1563 1563 Zinc 3; via carbamate group (By FT similarity). FT METAL 1597 1597 Zinc 3; via pros nitrogen (By FT similarity). FT METAL 1620 1620 Zinc 2 (By similarity). FT METAL 1621 1621 Zinc 3; via tele nitrogen (By FT similarity). FT METAL 1644 1644 Zinc 2 (By similarity). FT METAL 1693 1693 Zinc 1 (By similarity). FT BINDING 1482 1482 N-carbamoyl-L-aspartate (By similarity). FT BINDING 1512 1512 N-carbamoyl-L-aspartate (By similarity). FT BINDING 1668 1668 N-carbamoyl-L-aspartate; via amide FT nitrogen and carbonyl oxygen (By FT similarity). FT BINDING 1693 1693 N-carbamoyl-L-aspartate (By similarity). FT BINDING 1697 1697 N-carbamoyl-L-aspartate (By similarity). FT MOD_RES 1563 1563 N6-carboxylysine (By similarity). SQ SEQUENCE 2242 AA; 249393 MW; 99F1986BA41244EA CRC64; MATLFLDDGS SFKGRLFGAS STVSGEVVFQ TGMVGYPEAL TDPSYLSQIL VLTYPLIGNY GIPKDEEDEH GLSKWFESAK IHAAALVIGE NSQNPSHWSS VRSLDQRLKE HGIPALEGID TRSLTKKIRE KGTLLGKLVI DGTDENSLPY DDPNKRHLVK EVSIKEPKVY HPSGNVKIMA VDCGMKYNQI RSLCKRGAAV TVVPWDYLFD SNEFDGLFIS NGPGDPEYCQ QTINNVKKAI SEEKPKPLFG ICLGHQILSL AIGAKTYKMK YGNRGHNQPC IHEGTQRCFY TSQNHGFAVE PCSLPRDWSV LFTNANDQSN EGIIHNSKPL FSVQFHPEHK AGPTDLVDLF DIFLECARDV KLGVNLDKTV KGRVISHYSF KNGTENSKTP PGRIQPHKVL ILGSGGLSIG QAGEFDYSGS QAIKALKEEN VQSVLINPNI ATVQTSKGLA DKVYFLPITP EYVTQVIMNE RPDGILLTFG GQTALNCGVE LQKRGVLEKY HVRVLGTPVS SIEMTEDRKI FVEKMAEINE YVVPSEAAFT LEQAQGAAER LGYPVLVRAA FALGGLGSGF AQNKEELVTL VTQAFAHTSQ ILVDKSLKGW KEIEYEVVRD AYDNCITVCN MENVDPLGIH TGESIVVAPS QTLNDKEYNL LRTTAIKVIR HLGVVGECNI QYALSPESEQ YFIIEVNARL SRSSALASKA TGYPLAYVAA KLALGIPLPV LRNSVTNSTT ANYEPSLDYC VVKVPRWDLS KFLRLSTKIG SSMKSVGEVM AIGRNFEEAF QKALRMVDEN CVGFDHTLKP ASDEELETPT DKRIFVLAAA LRAGYEIDRL YELTKIDKWF LHKMKNIVEY SLKLSELYMK DEVPRHDLLK VKRLGFSDKQ IAMAIQSTEL AVRRLRQEWK ILPVVKQIDT VAAEWPAQTN YLYLTYNGEG HDLDFTKPHV MVIGSGVYRI GSSVEFDWCA VRCIQQLRKM GYKTRMVNYN PETVSTDYDM CDRLYFDEIS FEVVMDIYEL ENPEGIILSM GGQLPNNIAM DLHRQQCRIL GTSPESIDTA ENRFKFSRML DTIGISQPRW KELSDTESSK QFCTKVGYPC LIRPSYVLSG VAMNVAYSDN DLEKFLSSAV AVSKEHPVVI SKFIQEAKEI DVDAVACDGV VIAVAISEHV ENAGVHSGDA TLVTPPQDLN QKTTERIKAI VHAIGQELQA TGPFNLQLIA KDDQLKVIEC NVRVSRSFPF VSKTLGVDMI ALATKVIMGE EVEPVGLMTG TGVVGVKVPQ FSFSRLAGAD VVLGVEMTST GEVACFGENR YEAYLKAMLS TGFKIPKKNI LLSIGSYKNK SELLSTVQSL EQLGYNLYAS LGTADFYTEH GVKIKAVDWP FEDTDNGCPL KERHRNIMDY LEENHFDLVI NLSMRNSGGR RLSSFVTKGY RTRRLAVDYS VPLIIDIKCT KLFVEALRLV GDTPPVKTHI DSMSSHKLIR LPGLIDVHVH LREPGGTHKE DFASGTAAAL AGGVTMVCAM PNTNPAITDQ TSFALVQKLA TAGARCDFAL FLGASSDNAD VLPLISNSAA GLKMYLNDTF STLKMDNVSL WMEHFEKWPK HLPIVVHAER QTVAAILMVA QLYQRPVHIC HVARKEEIQI IRAAKQKGVQ VTCEVAPHHL FLNEEDLESI GHGKGQVRPM LSTKEDVNAL WENLDVIDCF ATDHAPHSVE EKNSDSPPPG YPGLETMLPL LLTAVSEGRL TIDDLVKRLY ENPRKIFSLP VQENTYVEVD LEQEWIIPSY MQFTKSKWTP FEGKKVKGRV RRVVLRGEVA YIDGQVLVPP GYGQDVRAWP LGVPLPPPPT TVKTPEHSKP TQTETVRTRT ASPRRLASSG PAVDARFHLP PRIHRCSDPG LPNAEGEYKE KPVKKFIEQD TVSQDGYIYP PPVSRLLSPQ NLAAQAVPHP YSLLLHPFVG QHILSVKRFT KDQLSHLFNV AHNLRLTVQK DRSLDILKGK VMASMFYEVS TRTSSSFRAA MHRLGGSVIH FSEATSSVQK GESLLDSVQT MSCYVDVVVL RHPEPGAVEL AAKHSRKPII NAGDGVGEHP TQALLDIFTI REELGTVNGM TITMVGDLKH GRTVHSLAYL LTLYRVNLRY VTPRNLRMPP NIIRFLASRG IKQEEFDSLE EALPDTDVLY MTRIQKERFA SEEEYEACFG QFILTPHIMT KGKKKMVVMH PLPRVNEVSV EVDSDPRAAY FRQAENGMYV RMALLATVLG KF //