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Database: UniProt
Entry: P27708
LinkDB: P27708
Original site: P27708 
ID   PYR1_HUMAN              Reviewed;        2225 AA.
AC   P27708; D6W552; Q6P0Q0; Q96CK3;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 3.
DT   01-OCT-2014, entry version 171.
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   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Fetal lung fibroblast;
RX   PubMed=8619816; DOI=10.1006/bbrc.1996.0213;
RA   Iwahana H., Fujimura M., Ii S., Kondo M., Moritani M., Takahashi Y.,
RA   Yamaoka T., Yoshimoto K., Itakura M.;
RT   "Molecular cloning of a human cDNA encoding a trifunctional enzyme of
RT   carbamoyl-phosphate synthetase-aspartate transcarbamoylase-
RT   dihydroorotase in de Novo pyrimidine synthesis.";
RL   Biochem. Biophys. Res. Commun. 219:249-255(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PROTEIN SEQUENCE OF 2-13; 157-165; 169-177; 359-371; 501-516; 548-555;
RP   599-606; 697-719; 761-778; 843-854; 932-944; 1034-1048; 1067-1075;
RP   1110-1127; 1229-1240; 1263-1270; 1313-1323; 1326-1333; 1658-1667;
RP   1723-1731; 1840-1848; 1976-1986; 2025-2036; 2103-2110; 2179-2187 AND
RP   2215-2225, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Colon adenocarcinoma, and Hepatoma;
RA   Bienvenut W.V., Dhillon A.S., Matallanas D., Murray L., Brunton V.G.,
RA   Cooper W.N., Boldt K., von Kriegsheim A.F., Kolch W., Frame M.C.;
RL   Submitted (FEB-2008) to UniProtKB.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1752-2225.
RX   PubMed=1979741; DOI=10.1089/dna.1990.9.667;
RA   Davidson J.N., Rao G.N., Niswander L., Andreano C., Tamer C.,
RA   Chen K.C.;
RT   "Organization and nucleotide sequence of the 3' end of the human CAD
RT   gene.";
RL   DNA Cell Biol. 9:667-676(1990).
RN   [6]
RP   MUTAGENESIS OF HIS-1471; HIS-1473; ASP-1512; HIS-1590; HIS-1642 AND
RP   HIS-1690, COFACTOR, AND ZINC-BINDING SITES.
RX   PubMed=7766613; DOI=10.1021/bi00021a015;
RA   Zimmermann B.H., Kemling N.M., Evans D.R.;
RT   "Function of conserved histidine residues in mammalian
RT   dihydroorotase.";
RL   Biochemistry 34:7038-7046(1995).
RN   [7]
RP   ENZYME REGULATION.
RX   PubMed=11872754; DOI=10.1074/jbc.M201112200;
RA   Sigoillot F.D., Evans D.R., Guy H.I.;
RT   "Growth-dependent regulation of mammalian pyrimidine biosynthesis by
RT   the protein kinase A and MAPK signaling cascades.";
RL   J. Biol. Chem. 277:15745-15751(2002).
RN   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15890648; DOI=10.1074/jbc.M504581200;
RA   Sigoillot F.D., Kotsis D.H., Serre V., Sigoillot S.M., Evans D.R.,
RA   Guy H.I.;
RT   "Nuclear localization and mitogen-activated protein kinase
RT   phosphorylation of the multifunctional protein CAD.";
RL   J. Biol. Chem. 280:25611-25620(2005).
RN   [9]
RP   INDUCTION.
RX   PubMed=16155188; DOI=10.1093/nar/gki839;
RA   Chen K.F., Lai Y.Y., Sun H.S., Tsai S.J.;
RT   "Transcriptional repression of human cad gene by hypoxia inducible
RT   factor-1alpha.";
RL   Nucleic Acids Res. 33:5190-5198(2005).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein
RT   phosphorylation analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [12]
RP   PHOSPHORYLATION AT THR-456; SER-1406; SER-1859 AND SER-1873, AND
RP   MUTAGENESIS OF SER-1873.
RX   PubMed=17485345; DOI=10.2741/2358;
RA   Sigoillot F.D., Kotsis D.H., Masko E.M., Bame M., Evans D.R.,
RA   Evans H.I.;
RT   "Protein kinase C modulates the up-regulation of the pyrimidine
RT   biosynthetic complex, CAD, by MAP kinase.";
RL   Front. Biosci. 12:3892-3898(2007).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859 AND THR-1884, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT   the kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1884, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [15]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [17]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-747 AND LYS-1411, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859; SER-1900 AND
RP   THR-1906, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [19]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1406 AND SER-1859, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [21]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.M111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C.,
RA   Meinnel T., Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [22]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA   Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA   Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-
RT   terminal acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [23]
RP   PHOSPHORYLATION AT SER-1859.
RX   PubMed=23429704; DOI=10.1126/science.1228771;
RA   Robitaille A.M., Christen S., Shimobayashi M., Cornu M., Fava L.L.,
RA   Moes S., Prescianotto-Baschong C., Sauer U., Jenoe P., Hall M.N.;
RT   "Quantitative phosphoproteomics reveal mTORC1 activates de novo
RT   pyrimidine synthesis.";
RL   Science 339:1320-1323(2013).
RN   [24]
RP   PHOSPHORYLATION AT SER-1859 AND SER-1900.
RX   PubMed=23429703; DOI=10.1126/science.1228792;
RA   Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D.;
RT   "Stimulation of de novo pyrimidine synthesis by growth signaling
RT   through mTOR and S6K1.";
RL   Science 339:1323-1328(2013).
RN   [25]
RP   X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1456-1846 IN COMPLEX WITH
RP   DIHYDROOROTATE; N-CARBAMOYL-L-ASPARTIC ACID AND ZINC, COFACTOR,
RP   CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP   MUTAGENESIS OF HIS-1471; THR-1562; PHE-1563; HIS-1590; CYS-1613;
RP   HIS-1614; GLU-1637 AND ASP-1686, AND CARBAMYLATION AT LYS-1556.
RX   PubMed=24332717; DOI=10.1016/j.str.2013.10.016;
RA   Grande-Garcia A., Lallous N., Diaz-Tejada C., Ramon-Maiques S.;
RT   "Structure, functional characterization, and evolution of the
RT   dihydroorotase domain of human CAD.";
RL   Structure 22:185-198(2014).
RN   [26]
RP   VARIANTS [LARGE SCALE ANALYSIS] GLN-177 AND CYS-735.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: This protein is a "fusion" protein encoding four
CC       enzymatic activities of the pyrimidine pathway (GATase, CPSase,
CC       ATCase and DHOase). {ECO:0000269|PubMed:24332717}.
CC   -!- CATALYTIC ACTIVITY: 2 ATP + L-glutamine + HCO(3)(-) + H(2)O = 2
CC       ADP + phosphate + L-glutamate + carbamoyl phosphate.
CC       {ECO:0000269|PubMed:24332717}.
CC   -!- CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate
CC       + N-carbamoyl-L-aspartate. {ECO:0000269|PubMed:24332717}.
CC   -!- CATALYTIC ACTIVITY: (S)-dihydroorotate + H(2)O = N-carbamoyl-L-
CC       aspartate. {ECO:0000269|PubMed:24332717}.
CC   -!- COFACTOR: Binds 3 zinc ions per subunit (for dihydroorotase
CC       activity). {ECO:0000269|PubMed:24332717,
CC       ECO:0000269|PubMed:7766613}.
CC   -!- ENZYME REGULATION: Allosterically regulated and controlled by
CC       phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an
CC       activator while UMP and UTP are inhibitors of the CPSase reaction.
CC       {ECO:0000269|PubMed:11872754}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=28 uM for dihydroorotate {ECO:0000269|PubMed:24332717};
CC         KM=241 uM for N-carbamoyl-L-aspartate
CC         {ECO:0000269|PubMed:24332717};
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. {ECO:0000269|PubMed:24332717}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15890648}.
CC       Nucleus {ECO:0000269|PubMed:15890648}. Note=Cytosolic and
CC       unphosphorylated in resting cells, translocates to the nucleus in
CC       response to EGF stimulation, nuclear import promotes optimal cell
CC       growth.
CC   -!- INDUCTION: Transcriptionally repressed following hypoxia by HIF1A.
CC       {ECO:0000269|PubMed:16155188}.
CC   -!- PTM: Activated by MAP kinase (Erk1/2) phosphorylation just prior
CC       to the S phase of the cell cycle, when the demand for pyrimidine
CC       nucleotides is greatest, and down-regulated as the cells emerge
CC       from S phase by protein kinase A (PKA) phosphorylation.
CC       Phosphorylation at Ser-1859 by RPS6KB1 downstream of MTOR promotes
CC       oligomerization and stimulates dihydroorotase activity.
CC       Phosphorylation at Ser-1406 reduces sensitivy to feedback
CC       inhibition by UTP. {ECO:0000269|PubMed:16964243,
CC       ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17485345,
CC       ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976,
CC       ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692,
CC       ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704}.
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       {ECO:0000305}.
CC   -!- SIMILARITY: Contains 2 ATP-grasp domains. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Aspartate carbamoyltransferase
CC       entry;
CC       URL="http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase";
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DR   EMBL; D78586; BAA11423.1; -; mRNA.
DR   EMBL; CH471053; EAX00612.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00613.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00614.1; -; Genomic_DNA.
DR   EMBL; BC014178; AAH14178.2; -; mRNA.
DR   EMBL; BC065510; AAH65510.1; -; mRNA.
DR   EMBL; M38561; AAA51907.1; -; Genomic_DNA.
DR   CCDS; CCDS1742.1; -.
DR   PIR; A36240; A36240.
DR   RefSeq; NP_004332.2; NM_004341.3.
DR   UniGene; Hs.377010; -.
DR   PDB; 4BY3; X-ray; 1.73 A; A=1456-1846.
DR   PDB; 4C6B; X-ray; 1.66 A; A=1456-1846.
DR   PDB; 4C6C; X-ray; 1.45 A; A=1456-1846.
DR   PDB; 4C6D; X-ray; 1.30 A; A=1456-1846.
DR   PDB; 4C6E; X-ray; 1.26 A; A=1456-1846.
DR   PDB; 4C6F; X-ray; 1.26 A; A=1456-1846.
DR   PDB; 4C6I; X-ray; 1.35 A; A=1456-1846.
DR   PDB; 4C6J; X-ray; 1.30 A; A=1456-1846.
DR   PDB; 4C6K; X-ray; 1.48 A; A=1456-1846.
DR   PDB; 4C6L; X-ray; 1.55 A; A=1456-1846.
DR   PDB; 4C6M; X-ray; 1.62 A; A=1456-1846.
DR   PDB; 4C6N; X-ray; 1.90 A; A=1456-1846.
DR   PDB; 4C6O; X-ray; 1.65 A; A=1456-1846.
DR   PDB; 4C6P; X-ray; 1.52 A; A=1456-1846.
DR   PDB; 4C6Q; X-ray; 1.66 A; A=1456-1846.
DR   PDBsum; 4BY3; -.
DR   PDBsum; 4C6B; -.
DR   PDBsum; 4C6C; -.
DR   PDBsum; 4C6D; -.
DR   PDBsum; 4C6E; -.
DR   PDBsum; 4C6F; -.
DR   PDBsum; 4C6I; -.
DR   PDBsum; 4C6J; -.
DR   PDBsum; 4C6K; -.
DR   PDBsum; 4C6L; -.
DR   PDBsum; 4C6M; -.
DR   PDBsum; 4C6N; -.
DR   PDBsum; 4C6O; -.
DR   PDBsum; 4C6P; -.
DR   PDBsum; 4C6Q; -.
DR   ProteinModelPortal; P27708; -.
DR   SMR; P27708; 2-359, 394-1823, 1923-2223.
DR   BioGrid; 107243; 41.
DR   DIP; DIP-39484N; -.
DR   IntAct; P27708; 23.
DR   MINT; MINT-5000537; -.
DR   STRING; 9606.ENSP00000264705; -.
DR   BindingDB; P27708; -.
DR   ChEMBL; CHEMBL3093; -.
DR   DrugBank; DB00128; L-Aspartic Acid.
DR   DrugBank; DB00130; L-Glutamine.
DR   MEROPS; C26.952; -.
DR   PhosphoSite; P27708; -.
DR   DMDM; 50403731; -.
DR   MaxQB; P27708; -.
DR   PaxDb; P27708; -.
DR   PeptideAtlas; P27708; -.
DR   PRIDE; P27708; -.
DR   Ensembl; ENST00000264705; ENSP00000264705; ENSG00000084774.
DR   GeneID; 790; -.
DR   KEGG; hsa:790; -.
DR   UCSC; uc002rji.3; human.
DR   CTD; 790; -.
DR   GeneCards; GC02P027440; -.
DR   HGNC; HGNC:1424; CAD.
DR   HPA; CAB007781; -.
DR   MIM; 114010; gene.
DR   neXtProt; NX_P27708; -.
DR   PharmGKB; PA26023; -.
DR   eggNOG; COG0458; -.
DR   HOGENOM; HOG000234584; -.
DR   HOVERGEN; HBG000279; -.
DR   InParanoid; P27708; -.
DR   KO; K11540; -.
DR   OMA; ACLQCWI; -.
DR   OrthoDB; EOG7M6D6F; -.
DR   PhylomeDB; P27708; -.
DR   TreeFam; TF105604; -.
DR   BioCyc; MetaCyc:ENSG00000084774-MONOMER; -.
DR   BRENDA; 3.5.2.3; 2681.
DR   Reactome; REACT_21376; Pyrimidine biosynthesis.
DR   UniPathway; UPA00070; UER00115.
DR   UniPathway; UPA00070; UER00116.
DR   UniPathway; UPA00070; UER00117.
DR   ChiTaRS; cad; human.
DR   GenomeRNAi; 790; -.
DR   NextBio; 3214; -.
DR   PMAP-CutDB; P27708; -.
DR   PRO; PR:P27708; -.
DR   ArrayExpress; P27708; -.
DR   Bgee; P27708; -.
DR   CleanEx; HS_CAD; -.
DR   Genevestigator; P27708; -.
DR   GO; GO:0042995; C:cell projection; ISS:BHF-UCL.
DR   GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR   GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProt.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISS:BHF-UCL.
DR   GO; GO:0016363; C:nuclear matrix; IDA:BHF-UCL.
DR   GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR   GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR   GO; GO:0043195; C:terminal bouton; ISS:BHF-UCL.
DR   GO; GO:0070335; F:aspartate binding; ISS:BHF-UCL.
DR   GO; GO:0004070; F:aspartate carbamoyltransferase activity; ISS:BHF-UCL.
DR   GO; GO:0005524; F:ATP binding; ISS:BHF-UCL.
DR   GO; GO:0004088; F:carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity; ISS:BHF-UCL.
DR   GO; GO:0004151; F:dihydroorotase activity; IDA:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL.
DR   GO; GO:0004672; F:protein kinase activity; ISS:BHF-UCL.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IDA: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:0035690; P:cellular response to drug; IEA:Ensembl.
DR   GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0017144; P:drug metabolic process; ISS:BHF-UCL.
DR   GO; GO:0009790; P:embryo development; IEA:Ensembl.
DR   GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR   GO; GO:0006543; P:glutamine catabolic process; IEA:InterPro.
DR   GO; GO:0006541; P:glutamine metabolic process; ISS:BHF-UCL.
DR   GO; GO:0007595; P:lactation; IEA:Ensembl.
DR   GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0031100; P:organ regeneration; IEA:Ensembl.
DR   GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:BHF-UCL.
DR   GO; GO:0046777; P:protein autophosphorylation; ISS:BHF-UCL.
DR   GO; GO:0006206; P:pyrimidine nucleobase metabolic process; TAS:Reactome.
DR   GO; GO:0046134; P:pyrimidine nucleoside biosynthetic process; TAS:Reactome.
DR   GO; GO:0014075; P:response to amine; IEA:Ensembl.
DR   GO; GO:0031000; P:response to caffeine; IEA:Ensembl.
DR   GO; GO:0051414; P:response to cortisol; IEA:Ensembl.
DR   GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0006228; P:UTP biosynthetic process; IEA:Ensembl.
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; -; 2.
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; 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; 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; 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.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Allosteric enzyme; ATP-binding;
KW   Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW   Ligase; Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Polymorphism; Pyrimidine biosynthesis;
KW   Reference proteome; Repeat; Transferase; Zinc.
FT   INIT_MET      1      1       Removed. {ECO:0000269|PubMed:19413330,
FT                                ECO:0000269|PubMed:22223895,
FT                                ECO:0000269|PubMed:22814378,
FT                                ECO:0000269|Ref.4}.
FT   CHAIN         2   2225       CAD protein.
FT                                /FTId=PRO_0000199506.
FT   DOMAIN      177    363       Glutamine amidotransferase type-1.
FT   DOMAIN      519    711       ATP-grasp 1.
FT   DOMAIN     1052   1243       ATP-grasp 2.
FT   REGION        2    365       GATase (Glutamine amidotransferase).
FT   REGION      366    394       Linker.
FT   REGION      395   1455       CPSase (Carbamoyl-phosphate synthase).
FT   REGION      395    933       CPSase A.
FT   REGION      934   1455       CPSase B.
FT   REGION     1456   1788       DHOase (dihydroorotase).
FT   REGION     1789   1917       Linker.
FT   REGION     1918   2225       ATCase (Aspartate transcarbamylase).
FT   ACT_SITE    252    252       For GATase activity. {ECO:0000250}.
FT   ACT_SITE    336    336       For GATase activity. {ECO:0000250}.
FT   ACT_SITE    338    338       For GATase activity. {ECO:0000250}.
FT   METAL      1471   1471       Zinc 1; via tele nitrogen.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1471   1471       Zinc 2; via pros nitrogen.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1473   1473       Zinc 1; via tele nitrogen.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1556   1556       Zinc 1; via carbamate group.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1556   1556       Zinc 3; via carbamate group.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1590   1590       Zinc 3; via pros nitrogen.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1613   1613       Zinc 2. {ECO:0000269|PubMed:24332717}.
FT   METAL      1614   1614       Zinc 3; via tele nitrogen.
FT                                {ECO:0000269|PubMed:24332717}.
FT   METAL      1637   1637       Zinc 2. {ECO:0000269|PubMed:24332717}.
FT   METAL      1686   1686       Zinc 1. {ECO:0000269|PubMed:24332717}.
FT   BINDING    1475   1475       N-carbamoyl-L-aspartate.
FT   BINDING    1505   1505       N-carbamoyl-L-aspartate.
FT   BINDING    1661   1661       N-carbamoyl-L-aspartate; via amide
FT                                nitrogen and carbonyl oxygen.
FT   BINDING    1686   1686       N-carbamoyl-L-aspartate.
FT   BINDING    1690   1690       N-carbamoyl-L-aspartate.
FT   MOD_RES       2      2       N-acetylalanine.
FT                                {ECO:0000269|PubMed:19413330,
FT                                ECO:0000269|PubMed:22223895,
FT                                ECO:0000269|PubMed:22814378,
FT                                ECO:0000269|Ref.4}.
FT   MOD_RES     456    456       Phosphothreonine; by MAPK1.
FT                                {ECO:0000269|PubMed:17485345}.
FT   MOD_RES     747    747       N6-acetyllysine.
FT                                {ECO:0000269|PubMed:19608861}.
FT   MOD_RES    1406   1406       Phosphoserine; by PKA.
FT                                {ECO:0000269|PubMed:17485345,
FT                                ECO:0000269|PubMed:21406692}.
FT   MOD_RES    1411   1411       N6-acetyllysine.
FT                                {ECO:0000269|PubMed:19608861}.
FT   MOD_RES    1556   1556       N6-carboxylysine.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MOD_RES    1859   1859       Phosphoserine; by RPS6KB1 and PKA.
FT                                {ECO:0000269|PubMed:16964243,
FT                                ECO:0000269|PubMed:17081983,
FT                                ECO:0000269|PubMed:17485345,
FT                                ECO:0000269|PubMed:18691976,
FT                                ECO:0000269|PubMed:20068231,
FT                                ECO:0000269|PubMed:21406692,
FT                                ECO:0000269|PubMed:23429703,
FT                                ECO:0000269|PubMed:23429704}.
FT   MOD_RES    1873   1873       Phosphoserine; by PKC; in vitro.
FT                                {ECO:0000269|PubMed:17485345}.
FT   MOD_RES    1884   1884       Phosphothreonine.
FT                                {ECO:0000269|PubMed:18669648,
FT                                ECO:0000269|PubMed:18691976}.
FT   MOD_RES    1900   1900       Phosphoserine.
FT                                {ECO:0000269|PubMed:20068231,
FT                                ECO:0000269|PubMed:23429703}.
FT   MOD_RES    1906   1906       Phosphothreonine.
FT                                {ECO:0000269|PubMed:20068231}.
FT   VARIANT     177    177       R -> Q (in a colorectal cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035897.
FT   VARIANT     735    735       Y -> C (in a colorectal cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035898.
FT   MUTAGEN    1471   1471       H->A: No zinc-binding and no catalytic
FT                                activity. {ECO:0000269|PubMed:24332717,
FT                                ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1471   1471       H->N: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717,
FT                                ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1473   1473       H->A: No zinc-binding and no catalytic
FT                                activity. {ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1512   1512       D->N: No change in catalytic activity.
FT                                {ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1562   1562       T->A: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MUTAGEN    1563   1563       F->A: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MUTAGEN    1590   1590       H->A: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717,
FT                                ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1590   1590       H->N: No catalytic activity.
FT                                {ECO:0000269|PubMed:24332717,
FT                                ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1613   1613       C->S: Reduces dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MUTAGEN    1614   1614       H->A: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MUTAGEN    1637   1637       E->T: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MUTAGEN    1642   1642       H->N: 11.5% of wild-type catalytic
FT                                activity. {ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1686   1686       D->N: Abolishes dihydroorotase activity.
FT                                {ECO:0000269|PubMed:24332717}.
FT   MUTAGEN    1690   1690       H->N: 3% of wild-type catalytic activity.
FT                                {ECO:0000269|PubMed:7766613}.
FT   MUTAGEN    1873   1873       S->A: Abolishes PMA-induced Thr-456
FT                                phosphorylation.
FT                                {ECO:0000269|PubMed:17485345}.
FT   CONFLICT    505    505       P -> T (in Ref. 1; BAA11423).
FT                                {ECO:0000305}.
FT   CONFLICT    535    535       A -> G (in Ref. 1; BAA11423).
FT                                {ECO:0000305}.
FT   CONFLICT    560    560       L -> V (in Ref. 1; BAA11423).
FT                                {ECO:0000305}.
FT   CONFLICT   1103   1103       T -> A (in Ref. 1; BAA11423).
FT                                {ECO:0000305}.
FT   CONFLICT   1513   1513       A -> G (in Ref. 1; BAA11423).
FT                                {ECO:0000305}.
FT   CONFLICT   1676   1676       N -> D (in Ref. 1; BAA11423).
FT                                {ECO:0000305}.
FT   STRAND     1462   1465
FT   STRAND     1467   1472
FT   TURN       1476   1478
FT   TURN       1480   1482
FT   HELIX      1485   1494
FT   STRAND     1497   1502
FT   STRAND     1506   1508
FT   HELIX      1513   1526
FT   STRAND     1528   1533
FT   TURN       1546   1548
FT   HELIX      1549   1551
FT   STRAND     1555   1558
FT   STRAND     1560   1563
FT   TURN       1564   1566
FT   HELIX      1571   1580
FT   STRAND     1587   1590
FT   HELIX      1594   1605
FT   STRAND     1610   1612
FT   HELIX      1618   1629
FT   STRAND     1634   1638
FT   HELIX      1640   1644
FT   HELIX      1647   1649
FT   HELIX      1650   1657
FT   HELIX      1667   1675
FT   HELIX      1677   1679
FT   HELIX      1692   1695
FT   STRAND     1697   1699
FT   HELIX      1707   1719
FT   HELIX      1725   1732
FT   HELIX      1734   1740
FT   STRAND     1749   1759
FT   TURN       1773   1776
FT   STRAND     1778   1788
FT   STRAND     1791   1795
FT   HELIX      1809   1811
FT   HELIX      1813   1815
SQ   SEQUENCE   2225 AA;  242984 MW;  2AB8E8413E825A8F CRC64;
     MAALVLEDGS VLRGQPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL VLTYPLIGNY
     GIPPDEMDEF GLCKWFESSG IHVAALVVGE CCPTPSHWSA TRTLHEWLQQ HGIPGLQGVD
     TRELTKKLRE QGSLLGKLVQ NGTEPSSLPF LDPNARPLVP EVSIKTPRVF NTGGAPRILA
     LDCGLKYNQI RCLCQRGAEV TVVPWDHALD SQEYEGLFLS NGPGDPASYP SVVSTLSRVL
     SEPNPRPVFG ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGSGRCFL TSQNHGFAVE
     TDSLPADWAP LFTNANDGSN EGIVHNSLPF FSVQFHPEHQ AGPSDMELLF DIFLETVKEA
     TAGNPGGQTV RERLTERLCP PGIPTPGSGL PPPRKVLILG SGGLSIGQAG EFDYSGSQAI
     KALKEENIQT LLINPNIATV QTSQGLADKV YFLPITPHYV TQVIRNERPD GVLLTFGGQT
     ALNCGVELTK AGVLARYGVR VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ
     AQAAAERLGY PVLVRAAFAL GGLGSGFASN REELSALVAP AFAHTSQVLV DKSLKGWKEI
     EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRQ TAIKVTQHLG
     IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY PLAYVAAKLA LGIPLPELRN
     SVTGGTAAFE PSVDYCVVKI PRWDLSKFLR VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL
     RMVDENCVGF DHTVKPVSDM ELETPTDKRI FVVAAALWAG YSVDRLYELT RIDRWFLHRM
     KRIIAHAQLL EQHRGQPLPP DLLQQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV
     KQIDTVAAEW PAQTNYLYLT YWGTTHDLTF RTPHVLVLGS GVYRIGSSVE FDWCAVGCIQ
     QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM DIYELENPEG VILSMGGQLP
     NNMAMALHRQ QCRVLGTSPE AIDSAENRFK FSRLLDTIGI SQPQWRELSD LESARQFCQT
     VGYPCVVRPS YVLSGAAMNV AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV
     ASDGVVAAIA ISEHVENAGV HSGDATLVTP PQDITAKTLE RIKAIVHAVG QELQVTGPFN
     LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR VIMGEEVEPV GLMTGSGVVG
     VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL KAMLSTGFKI PKKNILLTIG
     SYKNKSELLP TVRLLESLGY SLYASLGTAD FYTEHGVKVT AVDWHFEEAV DGECPPQRSI
     LEQLAEKNFE LVINLSMRGA GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL
     GQIGPAPPLK VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGITMV
     CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGTVAG SAAGLKLYLN
     ETFSELRLDS VVQWMEHFET WPSHLPIVAH AEQQTVAAVL MVAQLTQRSV HICHVARKEE
     ILLIKAAKAR GLPVTCEVAP HHLFLSHDDL ERLGPGKGEV RPELGSRQDV EALWENMAVI
     DCFASDHAPH TLEEKCGSRP PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF
     HLPPQEDTYV EVDLEHEWTI PSHMPFSKAH WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL
     VPPGYGQDVR KWPQGAVPQL PPSAPATSEM TTTPERPRRG IPGLPDGRFH LPPRIHRASD
     PGLPAEEPKE KSSRKVAEPE LMGTPDGTCY PPPPVPRQAS PQNLGTPGLL HPQTSPLLHS
     LVGQHILSVQ QFTKDQMSHL FNVAHTLRMM VQKERSLDIL KGKVMASMFY EVSTRTSSSF
     AAAMARLGGA VLSFSEATSS VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR
     PVINAGDGVG EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS
     LRYVAPPSLR MPPTVRAFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE RFGSTQEYEA
     CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR AAYFRQAENG MYIRMALLAT
     VLGRF
//
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