PYR1_SQUAC
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 03-AUG-2022, entry version 142.
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; Squalomorphii; 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 multifunctional
RT protein carbamoyl-phosphate synthetase-aspartate transcarbamoylase-
RT dihydroorotase (CAD) mRNA in Squalus acanthias.";
RL J. Biol. Chem. 270:14130-14139(1995).
CC -!- FUNCTION: This protein is a 'fusion' protein encoding four enzymatic
CC activities of the pyrimidine pathway (GATase, CPSase, ATCase and
CC DHOase).
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 -!- 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 -!- 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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 3 Zn(2+) ions per subunit (for dihydroorotase activity).
CC {ECO:0000250};
CC -!- ACTIVITY REGULATION: Allosterically regulated and controlled by
CC phosphorylation. 5-phosphoribose 1-diphosphate is an activator while
CC UMP is an inhibitor of the CPSase reaction (By similarity).
CC {ECO:0000250}.
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.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Present in the testis but not in the liver.
CC {ECO:0000269|PubMed:7775474}.
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}.
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 AlphaFoldDB; Q91437; -.
DR SMR; Q91437; -.
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:0006541; P:glutamine metabolic process; IEA:InterPro.
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 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
FT /note="CAD protein"
FT /id="PRO_0000199508"
FT DOMAIN 177..363
FT /note="Glutamine amidotransferase type-1"
FT DOMAIN 522..714
FT /note="ATP-grasp 1"
FT DOMAIN 1057..1248
FT /note="ATP-grasp 2"
FT DOMAIN 1313..1469
FT /note="MGS-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01202"
FT REGION 1..365
FT /note="GATase (Glutamine amidotransferase)"
FT REGION 366..397
FT /note="Linker"
FT REGION 398..1462
FT /note="CPSase (Carbamoyl-phosphate synthase)"
FT REGION 398..937
FT /note="CPSase A"
FT REGION 938..1462
FT /note="CPSase B"
FT REGION 1463..1796
FT /note="DHOase (dihydroorotase)"
FT REGION 1797..1934
FT /note="Linker"
FT REGION 1829..1862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1935..2242
FT /note="ATCase (Aspartate transcarbamylase)"
FT COMPBIAS 1835..1855
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 252
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 336
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 338
FT /note="For GATase activity"
FT /evidence="ECO:0000250"
FT BINDING 1478
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1478
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1480
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1482
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250"
FT BINDING 1512
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250"
FT BINDING 1563
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /note="via carbamate group"
FT /evidence="ECO:0000250"
FT BINDING 1563
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /note="via carbamate group"
FT /evidence="ECO:0000250"
FT BINDING 1597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1620
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1621
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1644
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1668
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250"
FT BINDING 1693
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250"
FT BINDING 1693
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1697
FT /ligand="N-carbamoyl-L-aspartate"
FT /ligand_id="ChEBI:CHEBI:32814"
FT /evidence="ECO:0000250"
FT MOD_RES 1563
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000250"
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
