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UniProtKB/Swiss-Prot entry P27708


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PYR1_HUMAN
Primary accession number P27708
Secondary accession number Q6P0Q0
Integrated into Swiss-Prot on August 1, 1992
Sequence was last modified on July 19, 2004 (Sequence version 3)
Annotations were last modified on    July 22, 2008 (Entry version 101)
Name and origin of the protein
Protein name CAD protein
Synonyms None
Includes Glutamine-dependent carbamoyl-phosphate synthase
     (EC 6.3.5.5)
Aspartate carbamoyltransferase
     (EC 2.1.3.2)
Dihydroorotase
     (EC 3.5.2.3)
Gene name
Name: CAD
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Fetal lung fibroblast;
DOI=10.1006/bbrc.1996.0213; PubMed=8619816 [NCBI, ExPASy, EBI, Israel, Japan]
Iwahana H., Fujimura M., Ii S., Kondo M., Moritani M., Takahashi Y., Yamaoka T., Yoshimoto K., Itakura M.;
"Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis.";
Biochem. Biophys. Res. Commun. 219:249-255(1996).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Eye;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
PROTEIN SEQUENCE OF 2-13; 157-165; 169-177; 359-371; 501-516; 548-555; 599-606; 697-719; 761-778; 843-854; 932-944; 1034-1048; 1067-1075; 1110-1127; 1229-1240; 1263-1270; 1313-1323; 1326-1333; 1658-1667; 1723-1731; 1840-1848; 1976-1986; 2025-2036; 2103-2110; 2179-2187 AND 2215-2225, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
TISSUE=Colon adenocarcinoma, and Hepatoma;
Bienvenut W.V., Dhillon A.S., Matallanas D., Murray L., Brunton V.G., Cooper W.N., Boldt K., von Kriegsheim A.F., Kolch W., Frame M.C.;
Submitted (FEB-2008) to UniProtKB.
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1752-2225.
PubMed=1979741 [NCBI, ExPASy, EBI, Israel, Japan]
Davidson J.N., Rao G.N., Niswander L., Andreano C., Tamer C., Chen K.C.;
"Organization and nucleotide sequence of the 3' end of the human CAD gene.";
DNA Cell Biol. 9:667-676(1990).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1823 AND SER-1859, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1423, AND MASS SPECTROMETRY.
DOI=10.2116/analsci.24.161; PubMed=18187866 [NCBI, ExPASy, EBI, Israel, Japan]
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Anal. Sci. 24:161-166(2008).
[8]
VARIANTS [LARGE SCALE ANALYSIS] GLN-177 AND CYS-735.
DOI=10.1126/science.1133427; PubMed=16959974 [NCBI, ExPASy, EBI, Israel, Japan]
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal cancers.";
Science 314:268-274(2006).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
D78586; BAA11423.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC065510; AAH65510.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M38561; AAA51907.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A36240; A36240.
RefSeq NP_004332.2; -.
UniGene Hs.377010
3D structure databases
HSSP P00479; 3CSU. [HSSP ENTRY / SWISS-3DIMAGE / PDB]
ModBase P27708.
Protein-protein interaction databases
IntAct P27708; -.
Protein family/group databases
MEROPS C26.952; -.
M38.972; -.
PTM databases
PhosphoSite P27708; -.
Enzyme and pathway databases
BioCyc MetaCyc:MON-11353; -.
Reactome REACT_1698; Nucleotide metabolism.
Organism-specific databases
H-InvDB HIX0001913; -.
HGNC HGNC:1424; CAD.
GenAtlas CAD.
HPA CAB007781; -.
MIM 114010; gene. [NCBI / EBI]
PharmGKB PA26023; -.
GeneCards P27708.
Gene expression databases
ArrayExpress P27708; -.
CleanEx HS_CAD; -.
GermOnline ENSG00000084774; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0004088; Molecular function: carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity (traceable author statement from ProtInc).
GO:0004151; Molecular function: dihydroorotase activity (inferred from experiment from Reactome).
QuickGo view.
Family and domain databases
InterPro IPR006680; Amidohydro_1.
IPR006220; Anth_synthII.
IPR006130; Asp/Orn_carbamoyltranf.
IPR006132; Asp/Orn_carbamoyltranf_P_bd.
IPR006131; Asp_carbamoyltransf_Asp/Orn_bd.
IPR002082; Aspartate_carbamoyltransf_euk.
IPR011761; ATP-grasp.
IPR013816; ATP_grasp_subdomain_2.
IPR001317; CarbamoylP_synth_GATase.
IPR005483; CarbamoylP_synth_lsu.
IPR005479; CarbamoylP_synth_lsu_ATP-bd.
IPR006275; CarbamoylP_synth_lsu_Gln-dep.
IPR005481; CarbamoylP_synth_lsu_N.
IPR005480; CarbamoylP_synth_lsu_oligo.
IPR006274; CarbamoylP_synth_ssu.
IPR002474; CarbamoylP_synth_ssu_N.
IPR004722; DHOmult.
IPR002195; Dihydroorotase_CS.
IPR011702; GATASE.
IPR012998; GATase_1_AS.
IPR000991; GATase_class1_C.
IPR011607; MGS.
IPR013817; Pre-ATP_grasp.
Graphical view of domain structure.
Gene3D G3DSA:3.30.470.20; ATP_grasp_subdomain_2; 2.
G3DSA:3.40.50.20; Pre-ATP_grasp; 2.
Pfam PF01979; Amidohydro_1; 1.
PF00289; CPSase_L_chain; 2.
PF02786; CPSase_L_D2; 2.
PF02787; CPSase_L_D3; 1.
PF00988; CPSase_sm_chain; 1.
PF00117; GATase; 1.
PF02142; MGS; 1.
PF00185; OTCace; 1.
PF02729; OTCace_N; 1.
Pfam graphical view of domain structure.
PRINTS PR00097; ANTSNTHASEII.
PR00100; AOTCASE.
PR00101; ATCASE.
PR00098; CPSASE.
PR00099; CPSGATASE.
PR00096; GATASE.
TIGRFAMs TIGR00670; asp_carb_tr; 1.
TIGR01369; CPSaseII_lrg; 1.
TIGR01368; CPSaseIIsmall; 1.
TIGR00857; pyrC_multi; 1.
PROSITE PS50975; ATP_GRASP; 2.
PS00097; CARBAMOYLTRANSFERASE; 1.
PS00866; CPSASE_1; 2.
PS00867; CPSASE_2; 2.
PS00482; DIHYDROOROTASE_1; 1.
PS00483; DIHYDROOROTASE_2; 1.
PS51273; GATASE_TYPE_1; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P27708.
Proteomic databases
PeptideAtlas P27708; -.
Genome annotation databases
Ensembl ENSG00000084774; Homo sapiens. [Contig view]
GeneID 790; -.
KEGG hsa:790; -.
Phylogenomic databases
HOGENOM P27708; -.
HOVERGEN P27708; -.
Other
DrugBank DB00128; L-Aspartic Acid.
DB00130; L-Glutamine.
SOURCE CAD; Homo sapiens.
ProtoNet P27708.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Acetylation; Allosteric enzyme; Cytoplasm; Direct protein sequencing; Hydrolase; Ligase; Metal-binding; Multifunctional enzyme; Phosphoprotein; Polymorphism; Pyrimidine biosynthesis; Repeat; Transferase; Zinc.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
INIT_MET   1      1        Removed. 
CHAIN   2   2225  2224     CAD protein. PRO_0000199506
DOMAIN   177    363  187     Glutamine amidotransferase type-1. 
DOMAIN   519    711  193     ATP-grasp 1. 
DOMAIN   1052   1243  192     ATP-grasp 2. 
REGION   2    365  364     GATase (Glutamine amidotransferase). 
REGION   366    394  29     Linker. 
REGION   395   1455  1061     CPSase (Carbamoyl-phosphate synthase). 
REGION   395    933  539     CPSase A. 
REGION   934   1455  522     CPSase B. 
REGION   1456   1788  333     DHOase (dihydroorotase). 
REGION   1789   1917  129     Linker. 
REGION   1918   2225  308     ATCase (Aspartate transcarbamylase). 
ACT_SITE   252    252        For GATase activity (By similarity). 
ACT_SITE   336    336        For GATase activity (By similarity). 
ACT_SITE   338    338        For GATase activity (By similarity). 
METAL   1471   1471        Zinc (Potential). 
METAL   1473   1473        Zinc (Potential). 
MOD_RES   2      2        N-acetylalanine. 
MOD_RES   1423   1423        Phosphoserine. 
MOD_RES   1823   1823        Phosphoserine. 
MOD_RES   1859   1859        Phosphoserine. 
VARIANT   177    177  1     R -> Q (in a colorectal cancer sample; somatic mutation). VAR_035897 
VARIANT   735    735  1     Y -> C (in a colorectal cancer sample; somatic mutation). VAR_035898 
CONFLICT   505    505        P -> T (in Ref. 1; BAA11423). 
CONFLICT   535    535        A -> G (in Ref. 1; BAA11423). 
CONFLICT   560    560        L -> V (in Ref. 1; BAA11423). 
CONFLICT   1103   1103        T -> A (in Ref. 1; BAA11423). 
CONFLICT   1513   1513        A -> G (in Ref. 1; BAA11423). 
CONFLICT   1676   1676        N -> D (in Ref. 1; BAA11423). 
Sequence information
Length: 2225 AA [This is the length of the unprocessed precursor] Molecular weight: 242984 Da [This is the MW of the unprocessed precursor] CRC64: 2AB8E8413E825A8F [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAALVLEDGS VLRGQPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL VLTYPLIGNY 

        70         80         90        100        110        120 
GIPPDEMDEF GLCKWFESSG IHVAALVVGE CCPTPSHWSA TRTLHEWLQQ HGIPGLQGVD 

       130        140        150        160        170        180 
TRELTKKLRE QGSLLGKLVQ NGTEPSSLPF LDPNARPLVP EVSIKTPRVF NTGGAPRILA 

       190        200        210        220        230        240 
LDCGLKYNQI RCLCQRGAEV TVVPWDHALD SQEYEGLFLS NGPGDPASYP SVVSTLSRVL 

       250        260        270        280        290        300 
SEPNPRPVFG ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGSGRCFL TSQNHGFAVE 

       310        320        330        340        350        360 
TDSLPADWAP LFTNANDGSN EGIVHNSLPF FSVQFHPEHQ AGPSDMELLF DIFLETVKEA 

       370        380        390        400        410        420 
TAGNPGGQTV RERLTERLCP PGIPTPGSGL PPPRKVLILG SGGLSIGQAG EFDYSGSQAI 

       430        440        450        460        470        480 
KALKEENIQT LLINPNIATV QTSQGLADKV YFLPITPHYV TQVIRNERPD GVLLTFGGQT 

       490        500        510        520        530        540 
ALNCGVELTK AGVLARYGVR VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ 

       550        560        570        580        590        600 
AQAAAERLGY PVLVRAAFAL GGLGSGFASN REELSALVAP AFAHTSQVLV DKSLKGWKEI 

       610        620        630        640        650        660 
EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRQ TAIKVTQHLG 

       670        680        690        700        710        720 
IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY PLAYVAAKLA LGIPLPELRN 

       730        740        750        760        770        780 
SVTGGTAAFE PSVDYCVVKI PRWDLSKFLR VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL 

       790        800        810        820        830        840 
RMVDENCVGF DHTVKPVSDM ELETPTDKRI FVVAAALWAG YSVDRLYELT RIDRWFLHRM 

       850        860        870        880        890        900 
KRIIAHAQLL EQHRGQPLPP DLLQQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV 

       910        920        930        940        950        960 
KQIDTVAAEW PAQTNYLYLT YWGTTHDLTF RTPHVLVLGS GVYRIGSSVE FDWCAVGCIQ 

       970        980        990       1000       1010       1020 
QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM DIYELENPEG VILSMGGQLP 

      1030       1040       1050       1060       1070       1080 
NNMAMALHRQ QCRVLGTSPE AIDSAENRFK FSRLLDTIGI SQPQWRELSD LESARQFCQT 

      1090       1100       1110       1120       1130       1140 
VGYPCVVRPS YVLSGAAMNV AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV 

      1150       1160       1170       1180       1190       1200 
ASDGVVAAIA ISEHVENAGV HSGDATLVTP PQDITAKTLE RIKAIVHAVG QELQVTGPFN 

      1210       1220       1230       1240       1250       1260 
LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR VIMGEEVEPV GLMTGSGVVG 

      1270       1280       1290       1300       1310       1320 
VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL KAMLSTGFKI PKKNILLTIG 

      1330       1340       1350       1360       1370       1380 
SYKNKSELLP TVRLLESLGY SLYASLGTAD FYTEHGVKVT AVDWHFEEAV DGECPPQRSI 

      1390       1400       1410       1420       1430       1440 
LEQLAEKNFE LVINLSMRGA GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL 

      1450       1460       1470       1480       1490       1500 
GQIGPAPPLK VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGITMV 

      1510       1520       1530       1540       1550       1560 
CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGTVAG SAAGLKLYLN 

      1570       1580       1590       1600       1610       1620 
ETFSELRLDS VVQWMEHFET WPSHLPIVAH AEQQTVAAVL MVAQLTQRSV HICHVARKEE 

      1630       1640       1650       1660       1670       1680 
ILLIKAAKAR GLPVTCEVAP HHLFLSHDDL ERLGPGKGEV RPELGSRQDV EALWENMAVI 

      1690       1700       1710       1720       1730       1740 
DCFASDHAPH TLEEKCGSRP PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF 

      1750       1760       1770       1780       1790       1800 
HLPPQEDTYV EVDLEHEWTI PSHMPFSKAH WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL 

      1810       1820       1830       1840       1850       1860 
VPPGYGQDVR KWPQGAVPQL PPSAPATSEM TTTPERPRRG IPGLPDGRFH LPPRIHRASD 

      1870       1880       1890       1900       1910       1920 
PGLPAEEPKE KSSRKVAEPE LMGTPDGTCY PPPPVPRQAS PQNLGTPGLL HPQTSPLLHS 

      1930       1940       1950       1960       1970       1980 
LVGQHILSVQ QFTKDQMSHL FNVAHTLRMM VQKERSLDIL KGKVMASMFY EVSTRTSSSF 

      1990       2000       2010       2020       2030       2040 
AAAMARLGGA VLSFSEATSS VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR 

      2050       2060       2070       2080       2090       2100 
PVINAGDGVG EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS 

      2110       2120       2130       2140       2150       2160 
LRYVAPPSLR MPPTVRAFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE RFGSTQEYEA 

      2170       2180       2190       2200       2210       2220 
CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR AAYFRQAENG MYIRMALLAT 


VLGRF 

P27708 in FASTA format

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