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P27708 (PYR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
CAD protein

Including the following 3 domains:

  1. Glutamine-dependent carbamoyl-phosphate synthase
    EC=6.3.5.5
  2. Aspartate carbamoyltransferase
    EC=2.1.3.2
  3. Dihydroorotase
    EC=3.5.2.3
Gene names
Name:CAD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2225 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). Ref.25

Catalytic activity

2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate. Ref.25

Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate. Ref.25

(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate. Ref.25

Cofactor

Binds 3 zinc ions per subunit (for dihydroorotase activity). Ref.6 Ref.25

Enzyme regulation

Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction. Ref.7

Pathway

Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3. HAMAP-Rule MF_00001

Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3.

Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3.

Subunit structure

Homohexamer.

Subcellular location

Cytoplasm. Nucleus. Note: Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth. Ref.8

Induction

Transcriptionally repressed following hypoxia by HIF1A. Ref.7 Ref.9

Post-translational modification

Activated by MAP kinase (Erk1/2) phosphorylation just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. Phosphorylation at Ser-1859 by RPS6KB1 downstream of MTOR promotes oligomerization and stimulates dihydroorotase activity. Phosphorylation at Ser-1406 reduces sensitivy to feedback inhibition by UTP. HAMAP-Rule MF_00001

Miscellaneous

GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC 6.3.5.5).

Sequence similarities

In the central section; belongs to the DHOase family.

Contains 2 ATP-grasp domains.

Contains 1 glutamine amidotransferase type-1 domain.

Biophysicochemical properties

Kinetic parameters:

KM=28 µM for dihydroorotate Ref.25

KM=241 µM for N-carbamoyl-L-aspartate

Ontologies

Keywords
   Biological processPyrimidine biosynthesis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionHydrolase
Ligase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_process'de novo' UMP biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

'de novo' pyrimidine nucleobase biosynthetic process

Inferred from direct assay Ref.25. Source: UniProtKB

UTP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

carbamoyl phosphate biosynthetic process

Inferred from electronic annotation. Source: InterPro

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

cellular response to epidermal growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

drug metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

embryo development

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

glutamine catabolic process

Inferred from electronic annotation. Source: InterPro

glutamine metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

lactation

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

organ regeneration

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

protein autophosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

pyrimidine nucleobase metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside biosynthetic process

Traceable author statement. Source: Reactome

response to amine

Inferred from electronic annotation. Source: Ensembl

response to caffeine

Inferred from electronic annotation. Source: Ensembl

response to cortisol

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcell projection

Inferred from sequence or structural similarity. Source: BHF-UCL

cytosol

Inferred from direct assay Ref.8. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

neuronal cell body

Inferred from sequence or structural similarity. Source: BHF-UCL

nuclear matrix

Inferred from direct assay PubMed 9525610. Source: BHF-UCL

nucleus

Inferred from direct assay Ref.8. Source: BHF-UCL

protein complex

Inferred from electronic annotation. Source: Ensembl

terminal bouton

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: BHF-UCL

aspartate binding

Inferred from sequence or structural similarity. Source: BHF-UCL

aspartate carbamoyltransferase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

Inferred from sequence or structural similarity. Source: BHF-UCL

dihydroorotase activity

Inferred from direct assay Ref.25. Source: UniProtKB

enzyme binding

Inferred from physical interaction PubMed 15326225. Source: UniProtKB

identical protein binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

zinc ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4
Chain2 – 22252224CAD protein HAMAP-Rule MF_00001
PRO_0000199506

Regions

Domain177 – 363187Glutamine amidotransferase type-1
Domain519 – 711193ATP-grasp 1
Domain1052 – 1243192ATP-grasp 2
Region2 – 365364GATase (Glutamine amidotransferase) HAMAP-Rule MF_00001
Region366 – 39429Linker HAMAP-Rule MF_00001
Region395 – 14551061CPSase (Carbamoyl-phosphate synthase) HAMAP-Rule MF_00001
Region395 – 933539CPSase A HAMAP-Rule MF_00001
Region934 – 1455522CPSase B HAMAP-Rule MF_00001
Region1456 – 1788333DHOase (dihydroorotase) HAMAP-Rule MF_00001
Region1789 – 1917129Linker HAMAP-Rule MF_00001
Region1918 – 2225308ATCase (Aspartate transcarbamylase) HAMAP-Rule MF_00001

Sites

Active site2521For GATase activity By similarity
Active site3361For GATase activity By similarity
Active site3381For GATase activity By similarity
Metal binding14711Zinc 1; via tele nitrogen
Metal binding14711Zinc 2; via pros nitrogen
Metal binding14731Zinc 1; via tele nitrogen
Metal binding15561Zinc 1; via carbamate group
Metal binding15561Zinc 3; via carbamate group
Metal binding15901Zinc 3; via pros nitrogen
Metal binding16131Zinc 2
Metal binding16141Zinc 3; via tele nitrogen
Metal binding16371Zinc 2
Metal binding16861Zinc 1
Binding site14751N-carbamoyl-L-aspartate
Binding site15051N-carbamoyl-L-aspartate
Binding site16611N-carbamoyl-L-aspartate; via amide nitrogen and carbonyl oxygen
Binding site16861N-carbamoyl-L-aspartate
Binding site16901N-carbamoyl-L-aspartate

Amino acid modifications

Modified residue21N-acetylalanine Ref.4 Ref.15 Ref.21 Ref.22
Modified residue4561Phosphothreonine; by MAPK1 Ref.12
Modified residue7471N6-acetyllysine Ref.17
Modified residue14061Phosphoserine; by PKA Ref.12 Ref.20
Modified residue14111N6-acetyllysine Ref.17
Modified residue15561N6-carboxylysine HAMAP-Rule MF_00001
Modified residue18591Phosphoserine; by RPS6KB1 and PKA Ref.10 Ref.11 Ref.12 Ref.13 Ref.18 Ref.20 Ref.23 Ref.24
Modified residue18731Phosphoserine; by PKC; in vitro Ref.12
Modified residue18841Phosphothreonine Ref.13 Ref.14
Modified residue19001Phosphoserine Ref.18 Ref.24
Modified residue19061Phosphothreonine Ref.18

Natural variations

Natural variant1771R → Q in a colorectal cancer sample; somatic mutation. Ref.26
VAR_035897
Natural variant7351Y → C in a colorectal cancer sample; somatic mutation. Ref.26
VAR_035898

Experimental info

Mutagenesis14711H → A: No zinc-binding and no catalytic activity. Ref.6 Ref.25
Mutagenesis14711H → N: Abolishes dihydroorotase activity. Ref.6 Ref.25
Mutagenesis14731H → A: No zinc-binding and no catalytic activity. Ref.6
Mutagenesis15121D → N: No change in catalytic activity. Ref.6
Mutagenesis15621T → A: Abolishes dihydroorotase activity. Ref.25
Mutagenesis15631F → A: Abolishes dihydroorotase activity. Ref.25
Mutagenesis15901H → A: Abolishes dihydroorotase activity. Ref.6 Ref.25
Mutagenesis15901H → N: No catalytic activity. Ref.6 Ref.25
Mutagenesis16131C → S: Reduces dihydroorotase activity. Ref.25
Mutagenesis16141H → A: Abolishes dihydroorotase activity. Ref.25
Mutagenesis16371E → T: Abolishes dihydroorotase activity. Ref.25
Mutagenesis16421H → N: 11.5% of wild-type catalytic activity. Ref.6
Mutagenesis16861D → N: Abolishes dihydroorotase activity. Ref.25
Mutagenesis16901H → N: 3% of wild-type catalytic activity. Ref.6
Mutagenesis18731S → A: Abolishes PMA-induced Thr-456 phosphorylation. Ref.12
Sequence conflict5051P → T in BAA11423. Ref.1
Sequence conflict5351A → G in BAA11423. Ref.1
Sequence conflict5601L → V in BAA11423. Ref.1
Sequence conflict11031T → A in BAA11423. Ref.1
Sequence conflict15131A → G in BAA11423. Ref.1
Sequence conflict16761N → D in BAA11423. Ref.1

Secondary structure

..................................................................... 2225
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P27708 [UniParc].

Last modified July 19, 2004. Version 3.
Checksum: 2AB8E8413E825A8F

FASTA2,225242,984
        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 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis."
Iwahana H., Fujimura M., Ii S., Kondo M., Moritani M., Takahashi Y., Yamaoka T., Yoshimoto K., Itakura M.
Biochem. Biophys. Res. Commun. 219:249-255(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal lung fibroblast.
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[4]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
Cited for: 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, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Colon adenocarcinoma and Hepatoma.
[5]"Organization and nucleotide sequence of the 3' end of the human CAD gene."
Davidson J.N., Rao G.N., Niswander L., Andreano C., Tamer C., Chen K.C.
DNA Cell Biol. 9:667-676(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1752-2225.
[6]"Function of conserved histidine residues in mammalian dihydroorotase."
Zimmermann B.H., Kemling N.M., Evans D.R.
Biochemistry 34:7038-7046(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HIS-1471; HIS-1473; ASP-1512; HIS-1590; HIS-1642 AND HIS-1690, COFACTOR, ZINC-BINDING SITES.
[7]"Growth-dependent regulation of mammalian pyrimidine biosynthesis by the protein kinase A and MAPK signaling cascades."
Sigoillot F.D., Evans D.R., Guy H.I.
J. Biol. Chem. 277:15745-15751(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[8]"Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD."
Sigoillot F.D., Kotsis D.H., Serre V., Sigoillot S.M., Evans D.R., Guy H.I.
J. Biol. Chem. 280:25611-25620(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha."
Chen K.F., Lai Y.Y., Sun H.S., Tsai S.J.
Nucleic Acids Res. 33:5190-5198(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[10]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Protein kinase C modulates the up-regulation of the pyrimidine biosynthetic complex, CAD, by MAP kinase."
Sigoillot F.D., Kotsis D.H., Masko E.M., Bame M., Evans D.R., Evans H.I.
Front. Biosci. 12:3892-3898(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-456; SER-1406; SER-1859 AND SER-1873, MUTAGENESIS OF SER-1873.
[13]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859 AND THR-1884, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1884, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-747 AND LYS-1411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1859; SER-1900 AND THR-1906, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1406 AND SER-1859, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis."
Robitaille A.M., Christen S., Shimobayashi M., Cornu M., Fava L.L., Moes S., Prescianotto-Baschong C., Sauer U., Jenoe P., Hall M.N.
Science 339:1320-1323(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1859.
[24]"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1."
Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D.
Science 339:1323-1328(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1859 AND SER-1900.
[25]"Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD."
Grande-Garcia A., Lallous N., Diaz-Tejada C., Ramon-Maiques S.
Structure 22:185-198(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1456-1846 IN COMPLEX WITH DIHYDROOROTATE; N-CARBAMOYL-L-ASPARTIC ACID AND ZINC, COFACTOR, CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-1471; THR-1562; PHE-1563; HIS-1590; CYS-1613; HIS-1614; GLU-1637 AND ASP-1686, CARBOXYLATION AT LYS-1556.
[26]"The consensus coding sequences of human breast and colorectal cancers."
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. expand/collapse author list , 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.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-177 AND CYS-735.
+Additional computationally mapped references.

Web resources

Wikipedia

Aspartate carbamoyltransferase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D78586 mRNA. Translation: BAA11423.1.
CH471053 Genomic DNA. Translation: EAX00612.1.
CH471053 Genomic DNA. Translation: EAX00613.1.
CH471053 Genomic DNA. Translation: EAX00614.1.
BC014178 mRNA. Translation: AAH14178.2.
BC065510 mRNA. Translation: AAH65510.1.
M38561 Genomic DNA. Translation: AAA51907.1.
PIRA36240.
RefSeqNP_004332.2. NM_004341.3.
UniGeneHs.377010.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4C6BX-ray1.66A1456-1846[»]
4C6CX-ray1.45A1456-1846[»]
4C6DX-ray1.30A1456-1846[»]
4C6EX-ray1.26A1456-1846[»]
4C6FX-ray1.26A1456-1846[»]
4C6IX-ray1.35A1456-1846[»]
4C6JX-ray1.30A1456-1846[»]
4C6KX-ray1.48A1456-1846[»]
4C6LX-ray1.55A1456-1846[»]
4C6MX-ray1.62A1456-1846[»]
4C6NX-ray1.90A1456-1846[»]
4C6OX-ray1.65A1456-1846[»]
4C6PX-ray1.52A1456-1846[»]
4C6QX-ray1.66A1456-1846[»]
ProteinModelPortalP27708.
SMRP27708. Positions 2-359, 394-1843, 1923-2223.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107243. 54 interactions.
DIPDIP-39484N.
IntActP27708. 23 interactions.
MINTMINT-5000537.
STRING9606.ENSP00000264705.

Chemistry

BindingDBP27708.
ChEMBLCHEMBL3093.
DrugBankDB00128. L-Aspartic Acid.
DB00130. L-Glutamine.

Protein family/group databases

MEROPSC26.952.

PTM databases

PhosphoSiteP27708.

Polymorphism databases

DMDM50403731.

Proteomic databases

PaxDbP27708.
PeptideAtlasP27708.
PRIDEP27708.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264705; ENSP00000264705; ENSG00000084774.
GeneID790.
KEGGhsa:790.
UCSCuc002rji.3. human.

Organism-specific databases

CTD790.
GeneCardsGC02P027440.
HGNCHGNC:1424. CAD.
HPACAB007781.
MIM114010. gene.
neXtProtNX_P27708.
PharmGKBPA26023.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0458.
HOGENOMHOG000234584.
HOVERGENHBG000279.
InParanoidP27708.
KOK11540.
OrthoDBEOG7M6D6F.
PhylomeDBP27708.
TreeFamTF105604.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000084774-MONOMER.
BRENDA3.5.2.3. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00070; UER00115.
UPA00070; UER00116.
UPA00070; UER00117.

Gene expression databases

ArrayExpressP27708.
BgeeP27708.
CleanExHS_CAD.
GenevestigatorP27708.

Family and domain databases

Gene3D1.10.1030.10. 1 hit.
3.30.1490.20. 1 hit.
3.30.470.20. 2 hits.
3.40.50.1370. 2 hits.
3.40.50.1380. 1 hit.
3.40.50.20. 2 hits.
3.50.30.20. 1 hit.
HAMAPMF_00001. Asp_carb_tr.
MF_01209. CPSase_S_chain.
InterProIPR006132. Asp/Orn_carbamoyltranf_P-bd.
IPR006130. Asp/Orn_carbamoylTrfase.
IPR002082. Asp_carbamoyltransf.
IPR006131. Asp_carbamoyltransf_Asp/Orn-bd.
IPR011761. ATP-grasp.
IPR013815. ATP_grasp_subdomain_1.
IPR013816. ATP_grasp_subdomain_2.
IPR006275. CarbamoylP_synth_lsu.
IPR005481. CarbamoylP_synth_lsu_N.
IPR005480. CarbamoylP_synth_lsu_oligo.
IPR006274. CarbamoylP_synth_ssu.
IPR002474. CarbamoylP_synth_ssu_N.
IPR005479. CbamoylP_synth_lsu-like_ATP-bd.
IPR005483. CbamoylP_synth_lsu_CPSase_dom.
IPR002195. Dihydroorotase_CS.
IPR017926. GATASE.
IPR011059. Metal-dep_hydrolase_composite.
IPR011607. MGS-like_dom.
IPR016185. PreATP-grasp_dom.
[Graphical view]
PfamPF00289. CPSase_L_chain. 2 hits.
PF02786. CPSase_L_D2. 2 hits.
PF02787. CPSase_L_D3. 1 hit.
PF00988. CPSase_sm_chain. 1 hit.
PF00117. GATase. 1 hit.
PF02142. MGS. 1 hit.
PF00185. OTCace. 1 hit.
PF02729. OTCace_N. 1 hit.
[Graphical view]
PRINTSPR00100. AOTCASE.
PR00101. ATCASE.
PR00098. CPSASE.
SMARTSM01096. CPSase_L_D3. 1 hit.
SM01097. CPSase_sm_chain. 1 hit.
SM00851. MGS. 1 hit.
[Graphical view]
SUPFAMSSF48108. SSF48108. 1 hit.
SSF51338. SSF51338. 1 hit.
SSF52021. SSF52021. 1 hit.
SSF52335. SSF52335. 1 hit.
SSF52440. SSF52440. 2 hits.
SSF53671. SSF53671. 1 hit.
TIGRFAMsTIGR00670. asp_carb_tr. 1 hit.
TIGR01369. CPSaseII_lrg. 1 hit.
TIGR01368. CPSaseIIsmall. 1 hit.
PROSITEPS50975. ATP_GRASP. 2 hits.
PS00097. CARBAMOYLTRANSFERASE. 1 hit.
PS00866. CPSASE_1. 2 hits.
PS00867. CPSASE_2. 2 hits.
PS00482. DIHYDROOROTASE_1. 1 hit.
PS00483. DIHYDROOROTASE_2. 1 hit.
PS51273. GATASE_TYPE_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRScad. human.
GenomeRNAi790.
NextBio3214.
PMAP-CutDBP27708.
PROP27708.
SOURCESearch...

Entry information

Entry namePYR1_HUMAN
AccessionPrimary (citable) accession number: P27708
Secondary accession number(s): D6W552, Q6P0Q0, Q96CK3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: July 19, 2004
Last modified: April 16, 2014
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM