CAD protein - Mesocricetus auratus (Golden hamster)

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P08955 (PYR1_MESAU) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 130. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
CAD protein

Including the following 3 domains:

Glutamine-dependent carbamoyl-phosphate synthase
EC=6.3.5.5
Aspartate carbamoyltransferase
EC=2.1.3.2
Dihydroorotase
EC=3.5.2.3

Gene names

Name:

CAD

Organism

Mesocricetus auratus (Golden hamster)

Taxonomic identifier

10036 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Mesocricetus

Protein attributes

Sequence length	2225 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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).
Catalytic activity	2 ATP + L-glutamine + HCO₃^- + H₂O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate. Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate. (S)-dihydroorotate + H₂O = N-carbamoyl-L-aspartate.
Cofactor	Binds 1 zinc ion per subunit (for dihydroorotase activity) Potential.
Enzyme regulation	Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate is an activator while UMP is an inhibitor of the CPSase reaction.
Pathway	Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3. 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.
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.

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Cellular component	Cytoplasm
Domain	Repeat
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase Ligase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Allosteric enzyme Direct protein sequencing Multifunctional enzyme
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 PubMed 19472. Source: BHF-UCL carbamoyl phosphate biosynthetic process Inferred from electronic annotation. Source: InterPro glutamine catabolic process Inferred from electronic annotation. Source: InterPro glutamine metabolic process Inferred from direct assay PubMed 19472. Source: BHF-UCL peptidyl-threonine phosphorylation Inferred from direct assay PubMed 11986331. Source: BHF-UCL protein autophosphorylation Inferred from direct assay PubMed 11986331. Source: BHF-UCL
Cellular_component	cytosol Inferred from direct assay PubMed 15890648. Source: BHF-UCL mitochondrion Inferred from direct assay PubMed 15890648. Source: BHF-UCL nuclear matrix Inferred from direct assay PubMed 15890648. Source: BHF-UCL
Molecular_function	ATP binding Inferred from direct assay PubMed 11986331. Source: BHF-UCL UTP binding Inferred from direct assay PubMed 11986331. Source: MGI aspartate binding Inferred from direct assay PubMed 19472. Source: BHF-UCL aspartate carbamoyltransferase activity Inferred from direct assay PubMed 19472. Source: BHF-UCL carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity Inferred from direct assay PubMed 19472. Source: BHF-UCL dihydroorotase activity Inferred from direct assay PubMed 19472. Source: BHF-UCL metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from direct assay PubMed 11986331. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 2225

2224

CAD protein

PRO_0000199507

Regions

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

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)

Sites

Active site

252

For GATase activity By similarity

Active site

336

For GATase activity By similarity

Active site

338

For GATase activity By similarity

Metal binding

1471

Zinc Potential

Metal binding

1473

Zinc Potential

Amino acid modifications

Modified residue

N-acetylalanine By similarity

Modified residue

747

N6-acetyllysine By similarity

Modified residue

1406

Phosphoserine By similarity

Modified residue

1411

N6-acetyllysine By similarity

Modified residue

1859

Phosphoserine By similarity

Modified residue

1884

Phosphothreonine By similarity

Modified residue

1900

Phosphoserine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

P08955 [UniParc].

Last modified August 1, 1992. Version 4.
Checksum: 9F6EBA9BD4C6EC5A
Show »

FASTA

2,225

243,128

        10         20         30         40         50         60 
MAALVLEDGS VLQGRPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL VLTYPLIGNY 

        70         80         90        100        110        120 
GIPSDEEDEF GLSKWFESSE NHVAGLVVGE CCPTPSHWSA TCTLHEWLQQ HGIPGLQGVD 

       130        140        150        160        170        180 
TRELTKKLRE QGSLLGKLVQ SGTEPSTLPF VDPNARPLAP EVSIKTPRVF NAGGAPRICA 

       190        200        210        220        230        240 
LDCGLKYNQI RCLCQLGAEV TVVPWNHELD SQKYDGLFLS NGPGDPASYP GVVATLNRVL 

       250        260        270        280        290        300 
SEPNPRPVFG ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGTGRCFL TSQNHGFAVD 

       310        320        330        340        350        360 
ADSLPAGWTP LFTNANDCSN EGIVHDSLPF FSVQFHPEHR AGPSDMELLF DVFLETVREA 

       370        380        390        400        410        420 
VAGNPGGQTV KERLVQRLCP PGLLIPGSGL 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 GGLGSGFAST KEELSALVAP AFAHTSQVLI DKSLKGWKEI 

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

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

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

       790        800        810        820        830        840 
RMVDENCVGF DHTVKPVSDV ELETPTDKRI FVVAAALWAG YSVERLYELT RIDCWFLHRM 

       850        860        870        880        890        900 
KRIVTHAQLL EQHRGQPLSQ DLLHQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV 

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

       970        980        990       1000       1010       1020 
QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM DIYELENPDG 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 
ACDGVVSAIA ISEHVENAGV HSGDATLVTP PQDITPKTLE RIKAIVHAVG QELQVTGPFN 

      1210       1220       1230       1240       1250       1260 
LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR IIMGEKVEPI 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 
LDQLAENHFE LVINLSMRGA GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL 

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

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

      1570       1580       1590       1600       1610       1620 
ETFSELRLDS VAQWMEHFET WPSHLPIVAH AERQSVAAVL MVAQLTQRPV HICHVARKEE 

      1630       1640       1650       1660       1670       1680 
ILLIKTAKAQ GLPVTCEVAP HHLFLNREDL ERLGPGRGEV RPELGSREDM EALWENMAVI 

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

      1750       1760       1770       1780       1790       1800 
HLPLQEDTYV EVDLEHEWTI PSHMPFSKAR WTPFEGQKVK GTIRRVVLRG EVAYIDGQVL 

      1810       1820       1830       1840       1850       1860 
VPPGYGQDVR KWPQGAVPQP PPSAPATTEI TTTPERPRRV IPGLPDGRFH LPPRIHRASD 

      1870       1880       1890       1900       1910       1920 
PGLPAEEPKE KPSRKVVEPE LMGTPDGPCY PAPPVPRQAS PQNLGSSGLL HPQTSPLLHS 

      1930       1940       1950       1960       1970       1980 
LVGQHILSVK 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 MPPSVWDFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE RFGSTQEYEA 

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


VLGRF

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References

[1]	"Molecular cloning of a cDNA encoding the amino end of the mammalian multifunctional protein CAD and analysis of the 5'-flanking region of the CAD gene." Bein K., Simmer J.P., Evans D.R. J. Biol. Chem. 266:3791-3799(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-169.
[2]	"Characterization of the 5' end of the growth-regulated Syrian hamster CAD gene." Farnham P.J., Kollmar R. Cell Growth Differ. 1:179-189(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-73.
[3]	"Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD." Simmer J.P., Kelly R.E., Rinker A.G. Jr., Scully J.L., Evans D.R. J. Biol. Chem. 265:10395-10402(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 156-1455.
[4]	"Identification of the junction between the glutamine amidotransferase and carbamyl phosphate synthetase domains of the mammalian CAD protein." Maley J.A., Davidson J.N. Biochem. Biophys. Res. Commun. 154:1047-1053(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 246-513.
[5]	"Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD." Simmer J.P., Kelly R.E., Rinker A.G. Jr., Zimmermann B.H., Scully J.L., Kim H., Evans D.R. Proc. Natl. Acad. Sci. U.S.A. 87:174-178(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1391-1870.
[6]	"Location of the dihydroorotase domain within trifunctional hamster dihydroorotate synthetase." Williams N.K., Simpson R.J., Moritz R.L., Peide Y., Crofts L., Minasian E., Leach S.J., Wake R.G., Christopherson R.I. Gene 94:283-288(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1403-2110.
[7]	"Mammalian aspartate transcarbamylase (ATCase): sequence of the ATCase domain and interdomain linker in the CAD multifunctional polypeptide and properties of the isolated domain." Simmer J.P., Kelly R.E., Scully J.L., Grayson D.R., Rinker A.G. Jr., Bergh S.T., Evans D.R. Proc. Natl. Acad. Sci. U.S.A. 86:4382-4386(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1774-2225.
[8]	"Construction of a cDNA to the hamster CAD gene and its application toward defining the domain for aspartate transcarbamylase." Shigesada K., Stark G.R., Maley J.A., Niswander L.A., Davidson J.N. Mol. Cell. Biol. 5:1735-1742(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2074-2225.
[9]	"The structural organization of the hamster multifunctional protein CAD. Controlled proteolysis, domains, and linkers." Kim H., Kelly R.E., Evans D.R. J. Biol. Chem. 267:7177-7184(1992) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS, PARTIAL PROTEIN SEQUENCE.
[10]	"Comparative modeling of mammalian aspartate transcarbamylase." Scully J.L., Evans D.R. Proteins 9:191-206(1991) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING OF ATCASE DOMAIN.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J05503 mRNA. Translation: AAA37062.1. M28866 mRNA. Translation: AAA37073.1. M60078 mRNA. Translation: AAA63617.1. M11242 mRNA. Translation: AAA37061.1. M23652 mRNA. Translation: AAA37064.1. M21927 mRNA. Translation: AAA37063.1.
PIR	A23443. A38653.
3D structure databases
ProteinModelPortal	P08955.
ModBase	Search...
Protein family/group databases
MEROPS	M38.972.
Proteomic databases
PRIDE	P08955.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG000279.
Enzyme and pathway databases
BRENDA	3.5.2.3. 3239.
SABIO-RK	P08955.
UniPathway	UPA00070; UER00115. UPA00070; UER00116. UPA00070; UER00117.
Family and domain databases
Gene3D	1.10.1030.10. 1 hit. 3.30.1490.20. 1 hit. 3.30.470.20. 2 hits. 3.40.50.1380. 1 hit. 3.40.50.20. 2 hits. 3.50.30.20. 1 hit.
InterPro	IPR006132. 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_1. IPR011059. Metal-dep_hydrolase_composite. IPR011607. MGS-like_dom. IPR016185. PreATP-grasp_dom. [Graphical view]
Pfam	PF00289. 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]
PRINTS	PR00100. AOTCASE. PR00101. ATCASE. PR00098. CPSASE.
SMART	SM01096. CPSase_L_D3. 1 hit. SM01097. CPSase_sm_chain. 1 hit. SM00851. MGS. 1 hit. [Graphical view]
SUPFAM	SSF53671. Asp/Orn_carbamoyltranf. 1 hit. SSF48108. CarbamoylP_synth_lsu_oligo. 1 hit. SSF52021. CP_synthsmall. 1 hit. SSF51338. Metalo_hydrolase. 1 hit. SSF52335. MGS-like_dom. 1 hit. SSF52440. PreATP-grasp-like. 2 hits.
TIGRFAMs	TIGR00670. asp_carb_tr. 1 hit. TIGR01369. CPSaseII_lrg. 1 hit. TIGR01368. CPSaseIIsmall. 1 hit.
PROSITE	PS50975. 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]
ProtoNet	Search...

Entry information

Entry name

PYR1_MESAU

Accession

Primary (citable) accession number: P08955
Secondary accession number(s): P70108

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	August 1, 1992
Last modified:	April 3, 2013
This is version 130 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Including the following 3 domains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

Proteomic databases

Protocols and materials databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents