ID PYR1_SQUAC STANDARD; PRT; 2242 AA. AC Q91437; DT 15-JUL-1998 (Rel. 36, Created) DT 15-JUL-1998 (Rel. 36, Last sequence update) DT 05-JUL-2004 (Rel. 44, Last annotation update) DE CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate DE synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); DE Dihydroorotase (EC 3.5.2.3)]. GN Name=CAD; OS Squalus acanthias (Spiny dogfish). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Chondrichthyes; OC Elasmobranchii; Squalea; Hypnosqualea; Squaliformes; Squaloidei; OC Squalidae; Squalus. OX NCBI_TaxID=7797; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Spleen, and Testis; RX MEDLINE=95294021; 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 + CO(2) + H(2)O = 2 ADP + CC 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: Dihydroorotase: binds 1 zinc ion per subunit CC (Potential). CC -!- ENZYME REGULATION: Allosterically regulated and controlled by CC phosphorylation. PRPP is an activator while UMP is an inhibitor of CC the CPSase reaction (By similarity). CC -!- PATHWAY: Pyrimidine biosynthesis; first step. CC -!- PATHWAY: Pyrimidine biosynthesis; second step. CC -!- PATHWAY: Pyrimidine biosynthesis; third step. CC -!- SUBUNIT: Homohexamer. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. 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 type-1 glutamine amidotransferase 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; -. DR PIR; A57541; A57541. DR HSSP; P77918; 1ML4. DR InterPro; IPR006680; Amidohydro_1. DR InterPro; IPR006220; Anth_synthII. DR InterPro; IPR006131; Asp/Orn-bind. DR InterPro; IPR006130; Asp/Orn_COtranf. DR InterPro; IPR002082; Asp_carbmltransf. DR InterPro; IPR006275; CarA_L_glu. DR InterPro; IPR006274; CarA_synth_small. DR InterPro; IPR001317; CP_synthGATase. DR InterPro; IPR002474; CP_synthsmall. DR InterPro; IPR005483; CPase_L. DR InterPro; IPR005480; CPase_L_D3. DR InterPro; IPR005481; CPase_L_N. DR InterPro; IPR005479; Cphp_synth_L_D2. DR InterPro; IPR005847; DHOase. DR InterPro; IPR004722; DHOmult. DR InterPro; IPR002195; Dihydroorotase. DR InterPro; IPR000991; GATase_1. DR InterPro; IPR004362; MG_synth_like. DR InterPro; IPR006132; OTCace_P. 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; PR00097; ANTSNTHASEII. DR PRINTS; PR00100; AOTCASE. DR PRINTS; PR00101; ATCASE. DR PRINTS; PR00098; CPSASE. DR PRINTS; PR00099; CPSGATASE. DR PRINTS; PR00096; GATASE. DR TIGRFAMs; TIGR00670; asp_carb_tr; 1. DR TIGRFAMs; TIGR01369; CPSaseII_lrg; 1. DR TIGRFAMs; TIGR01368; CPSaseIIsmall; 1. DR TIGRFAMs; TIGR00857; pyrC_multi; 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; PS00442; GATASE_TYPE_I; 1. KW Allosteric enzyme; Hydrolase; Ligase; Multifunctional enzyme; KW Phosphorylation; Pyrimidine biosynthesis; Repeat; Transferase; Zinc. FT DOMAIN 1 365 GATase (Glutamine amidotransferase). FT DOMAIN 366 397 Linker. FT DOMAIN 398 1462 CPSase (Carbamoyl-phosphate synthase). FT DOMAIN 398 937 CPSase A. FT DOMAIN 522 714 ATP-grasp 1. FT DOMAIN 938 1462 CPSase B. FT DOMAIN 1057 1248 ATP-grasp 2. FT DOMAIN 1463 1796 DHOase (dihydroorotase). FT DOMAIN 1797 1934 Linker. FT DOMAIN 1935 2242 ATCase (Aspartate transcarbamylase). FT ACT_SITE 252 252 GATase (By similarity). FT ACT_SITE 336 336 GATase (By similarity). FT ACT_SITE 338 338 GATase (By similarity). FT METAL 1478 1478 Zinc (Potential). FT METAL 1480 1480 Zinc (Potential). SQ SEQUENCE 2242 AA; 249391 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 //