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Protein

CAD protein

Gene

Cad

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

Miscellaneous

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

Catalytic activityi

2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate.By similarity
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate.By similarity
(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate.By similarity

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 3 Zn2+ ions per subunit (for dihydroorotase activity).By similarity
  • Mg2+PROSITE-ProRule annotation, Mn2+PROSITE-ProRule annotationNote: Binds 4 magnesium or manganese ions per subunit.PROSITE-ProRule annotation

Enzyme regulationi

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

Pathwayi: UMP biosynthesis via de novo pathway

This protein is involved in step 1, 2 and 3 of the subpathway that synthesizes (S)-dihydroorotate from bicarbonate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. CAD protein (Cad)
  2. CAD protein (Cad)
  3. CAD protein (Cad)
This subpathway is part of the pathway UMP biosynthesis via de novo pathway, which is itself part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-dihydroorotate from bicarbonate, the pathway UMP biosynthesis via de novo pathway and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei252Nucleophile; for GATase activityPROSITE-ProRule annotation1
Active sitei336For GATase activityPROSITE-ProRule annotation1
Active sitei338For GATase activityPROSITE-ProRule annotation1
Metal bindingi668Magnesium or manganese 1PROSITE-ProRule annotation1
Metal bindingi682Magnesium or manganese 1PROSITE-ProRule annotation1
Metal bindingi682Magnesium or manganese 2PROSITE-ProRule annotation1
Metal bindingi684Magnesium or manganese 2PROSITE-ProRule annotation1
Metal bindingi1202Magnesium or manganese 3PROSITE-ProRule annotation1
Metal bindingi1214Magnesium or manganese 3PROSITE-ProRule annotation1
Metal bindingi1214Magnesium or manganese 4PROSITE-ProRule annotation1
Metal bindingi1216Magnesium or manganese 4PROSITE-ProRule annotation1
Metal bindingi1471Zinc 1; via tele nitrogenBy similarity1
Metal bindingi1471Zinc 2; via pros nitrogenBy similarity1
Metal bindingi1473Zinc 1; via tele nitrogenBy similarity1
Binding sitei1475N-carbamoyl-L-aspartateBy similarity1
Binding sitei1505N-carbamoyl-L-aspartateBy similarity1
Metal bindingi1556Zinc 1; via carbamate groupBy similarity1
Metal bindingi1556Zinc 3; via carbamate groupBy similarity1
Metal bindingi1590Zinc 3; via pros nitrogenBy similarity1
Metal bindingi1613Zinc 2By similarity1
Metal bindingi1614Zinc 3; via tele nitrogenBy similarity1
Metal bindingi1637Zinc 2By similarity1
Binding sitei1661N-carbamoyl-L-aspartate; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi1686Zinc 1By similarity1
Binding sitei1686N-carbamoyl-L-aspartateBy similarity1
Binding sitei1690N-carbamoyl-L-aspartateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi545 – 600ATPPROSITE-ProRule annotationAdd BLAST56
Nucleotide bindingi1078 – 1135ATPPROSITE-ProRule annotationAdd BLAST58

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Hydrolase, Ligase, Multifunctional enzyme, Transferase
Biological processPyrimidine biosynthesis
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-500753 Pyrimidine biosynthesis
UniPathwayiUPA00070; UER00115
UPA00070; UER00116
UPA00070; UER00117

Names & Taxonomyi

Protein namesi
Recommended name:
CAD protein
Including the following 3 domains:
Glutamine-dependent carbamoyl-phosphate synthase (EC:6.3.5.5By similarity)
Aspartate carbamoyltransferase (EC:2.1.3.2By similarity)
Dihydroorotase (EC:3.5.2.3By similarity)
Gene namesi
Name:Cad
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1916969 Cad

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2774

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004259552 – 2225CAD proteinAdd BLAST2224

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei456Phosphothreonine; by MAPK1By similarity1
Modified residuei747N6-acetyllysineBy similarity1
Modified residuei1038PhosphoserineBy similarity1
Modified residuei1406Phosphoserine; by PKABy similarity1
Modified residuei1411N6-acetyllysineBy similarity1
Modified residuei1556N6-carboxylysineBy similarity1
Modified residuei1859PhosphoserineCombined sources1
Modified residuei1884PhosphothreonineBy similarity1
Modified residuei1900PhosphoserineBy similarity1
Modified residuei1938PhosphoserineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiB2RQC6
MaxQBiB2RQC6
PaxDbiB2RQC6
PeptideAtlasiB2RQC6
PRIDEiB2RQC6

PTM databases

iPTMnetiB2RQC6
PhosphoSitePlusiB2RQC6
SwissPalmiB2RQC6

Expressioni

Gene expression databases

BgeeiENSMUSG00000013629
ExpressionAtlasiB2RQC6 baseline and differential
GenevisibleiB2RQC6 MM

Interactioni

Subunit structurei

Homohexamer. Interacts with CIPC.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi213636, 11 interactors
DIPiDIP-61412N
IntActiB2RQC6, 12 interactors
STRINGi10090.ENSMUSP00000013773

Chemistry databases

BindingDBiB2RQC6

Structurei

3D structure databases

ProteinModelPortaliB2RQC6
SMRiB2RQC6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini177 – 363Glutamine amidotransferase type-1PROSITE-ProRule annotationAdd BLAST187
Domaini519 – 711ATP-grasp 1PROSITE-ProRule annotationAdd BLAST193
Domaini1052 – 1243ATP-grasp 2PROSITE-ProRule annotationAdd BLAST192
Domaini1308 – 1462MGS-likePROSITE-ProRule annotationAdd BLAST155

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 365GATase (Glutamine amidotransferase)By similarityAdd BLAST364
Regioni366 – 394LinkerBy similarityAdd BLAST29
Regioni395 – 1455CPSase (Carbamoyl-phosphate synthase)By similarityAdd BLAST1061
Regioni395 – 933CPSase ABy similarityAdd BLAST539
Regioni934 – 1455CPSase BBy similarityAdd BLAST522
Regioni1456 – 1788DHOase (dihydroorotase)By similarityAdd BLAST333
Regioni1789 – 1917LinkerBy similarityAdd BLAST129
Regioni1918 – 2225ATCase (Aspartate transcarbamylase)By similarityAdd BLAST308

Sequence similaritiesi

In the central section; belongs to the metallo-dependent hydrolases superfamily. DHOase family. CAD subfamily.Curated

Keywords - Domaini

Glutamine amidotransferase, Repeat

Phylogenomic databases

eggNOGiKOG0370 Eukaryota
COG0458 LUCA
COG0505 LUCA
COG0540 LUCA
GeneTreeiENSGT00910000144175
HOGENOMiHOG000234584
HOVERGENiHBG000279
InParanoidiB2RQC6
KOiK11540
OMAiNIPCTSM
OrthoDBiEOG091G00DC
PhylomeDBiB2RQC6
TreeFamiTF105604

Family and domain databases

CDDicd01744 GATase1_CPSase, 1 hit
Gene3Di1.10.1030.10, 1 hit
3.30.1490.20, 1 hit
3.40.50.1370, 3 hits
3.40.50.1380, 1 hit
3.40.50.880, 1 hit
3.50.30.20, 1 hit
HAMAPiMF_00001 Asp_carb_tr, 1 hit
MF_01209 CPSase_S_chain, 1 hit
InterProiView protein in InterPro
IPR006680 Amidohydro-rel
IPR006132 Asp/Orn_carbamoyltranf_P-bd
IPR006130 Asp/Orn_carbamoylTrfase
IPR036901 Asp/Orn_carbamoylTrfase_sf
IPR002082 Asp_carbamoyltransf
IPR006131 Asp_carbamoyltransf_Asp/Orn-bd
IPR011761 ATP-grasp
IPR013815 ATP_grasp_subdomain_1
IPR006275 CarbamoylP_synth_lsu
IPR005480 CarbamoylP_synth_lsu_oligo
IPR036897 CarbamoylP_synth_lsu_oligo_sf
IPR006274 CarbamoylP_synth_ssu
IPR002474 CarbamoylP_synth_ssu_N
IPR036480 CarbP_synth_ssu_N_sf
IPR005479 CbamoylP_synth_lsu-like_ATP-bd
IPR005483 CbamoylP_synth_lsu_CPSase_dom
IPR029062 Class_I_gatase-like
IPR035686 CPSase_GATase1
IPR002195 Dihydroorotase_CS
IPR017926 GATASE
IPR011059 Metal-dep_hydrolase_composite
IPR032466 Metal_Hydrolase
IPR011607 MGS-like_dom
IPR036914 MGS-like_dom_sf
IPR016185 PreATP-grasp_dom_sf
PfamiView protein in Pfam
PF01979 Amidohydro_1, 1 hit
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
PRINTSiPR00100 AOTCASE
PR00101 ATCASE
PR00098 CPSASE
SMARTiView protein in SMART
SM01096 CPSase_L_D3, 1 hit
SM01097 CPSase_sm_chain, 1 hit
SM00851 MGS, 1 hit
SUPFAMiSSF48108 SSF48108, 1 hit
SSF51338 SSF51338, 1 hit
SSF51556 SSF51556, 1 hit
SSF52021 SSF52021, 1 hit
SSF52317 SSF52317, 1 hit
SSF52335 SSF52335, 1 hit
SSF52440 SSF52440, 2 hits
SSF53671 SSF53671, 1 hit
TIGRFAMsiTIGR00670 asp_carb_tr, 1 hit
TIGR01369 CPSaseII_lrg, 1 hit
TIGR01368 CPSaseIIsmall, 1 hit
PROSITEiView protein in 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
PS51855 MGS, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: B2RQC6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAALVLEDGS VLQGRPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL
60 70 80 90 100
VLTYPLIGNY GIPSDEEDEF GLSKWFESSE IHVAGLVVGE CCPTPSHWSA
110 120 130 140 150
NCTLHEWLQQ RGIPGLQGVD TRELTKKLRE QGSLLGKLVQ KGTEPSALPF
160 170 180 190 200
VDPNARPLAP EVSIKTPRVF NAGGAPRICA LDCGLKYNQI RCLCQLGAEV
210 220 230 240 250
TVVPWDHELD SQKYDGLFLS NGPGDPASYP GVVSTLSRVL SEPNPRPVFG
260 270 280 290 300
ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGTGRCFL TSQNHGFAVD
310 320 330 340 350
ADSLPAGWAP LFTNANDCSN EGIVHDSLPF FSVQFHPEHR AGPSDMELLF
360 370 380 390 400
DVFLETVREA AAGNIGGQTV RERLAQRLCP PELPIPGSGL PPPRKVLILG
410 420 430 440 450
SGGLSIGQAG EFDYSGSQAI KALKEENIQT LLINPNIATV QTSQGLADKV
460 470 480 490 500
YFLPITLHYV TQVIRNERPD GVLLTFGGQT ALNCGVELTK AGVLARYGVR
510 520 530 540 550
VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ AQAAAERLGY
560 570 580 590 600
PVLVRAAFAL GGLGSGFAST KEELSALVAP AFAHTSQVLI DKSLKGWKEI
610 620 630 640 650
EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRR
660 670 680 690 700
TAIKVTQHLG IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY
710 720 730 740 750
PLAYVAAKLA LGIPLPELRN SVTGGTAAFE PSLDYCVVKI PRWDLSKFLR
760 770 780 790 800
VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL RMVDENCVGF DHTVKPVSDM
810 820 830 840 850
ELETPTDKRI FVVAAALWAG YSVERLYELT RIDCWFLHRM KRIVTHAQLL
860 870 880 890 900
EQHRGQALPQ DLLHQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV
910 920 930 940 950
KQIDTVAAEW PAQTNYLYLT YWGNTHDLDF RAPHVLVLGS GVYRIGSSVE
960 970 980 990 1000
FDWCAVGCIQ QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM
1010 1020 1030 1040 1050
DIYELENPEG VILSMGGQLP NNMAMALHRQ QCRVLGTSPE AIDSAENRFK
1060 1070 1080 1090 1100
FSRLLDTIGI SQPQWRELSD LESARQFCHT VGYPCVVRPS YVLSGAAMNV
1110 1120 1130 1140 1150
AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV ACDGIVSAIA
1160 1170 1180 1190 1200
ISEHVENAGV HSGDATLVTP PQDITPKTLE RIKAIVHAVG QELQVTGPFN
1210 1220 1230 1240 1250
LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR IIMGEKVEPV
1260 1270 1280 1290 1300
GLMTGSGVVG VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL
1310 1320 1330 1340 1350
KAMLSTGFKI PEKNILLTIG SYKNKSELLP TVRLLESLGY SLYASLGTAD
1360 1370 1380 1390 1400
FYTEHGVKVT AVDWHFEEAV DGECPPQRSI LDQLAENHFE LVINLSMRGA
1410 1420 1430 1440 1450
GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL GQIGPAPPLK
1460 1470 1480 1490 1500
VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGVTMV
1510 1520 1530 1540 1550
CAMPNTRPPI IDAPALALAQ KLAEAGARCD FTLFLGASSE NAGTLGAVAG
1560 1570 1580 1590 1600
SAAGLKLYLN ETFSELRLDS VAQWMEHFET WPAHLPIVAH AERQSVAAVL
1610 1620 1630 1640 1650
MVAQLTQRPV HICHVARKEE ILLIKTAKAQ GLPVTCEVAP HHLFLNREDL
1660 1670 1680 1690 1700
ERLGPGKGEV RPELGSREDM EALWENMAVI DCFASDHAPH TLEEKCGPKP
1710 1720 1730 1740 1750
PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF HLPLQEDTYV
1760 1770 1780 1790 1800
EVDLEHEWTV PSHMPFSKAR WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL
1810 1820 1830 1840 1850
VPPGYGQDVR KWPQGVVPQP PPSTPATTEI TTTPERPRRV IPGLPDGRFH
1860 1870 1880 1890 1900
LPPRIHRASD PGLPAEEPKE KPPRKVVEPE LMGTPDGPCY PAPPVPRQAS
1910 1920 1930 1940 1950
PQNLGSSGLL HPQMSPLLHS LVGQHILSVK QFTKDQMSHL FNVAHTLRMM
1960 1970 1980 1990 2000
VQKERSLDIL KGKVMASMFY EVSTRTSSSF AAAMARLGGA VLSFSEATSS
2010 2020 2030 2040 2050
VQKGESLADS VQTMSCYADV IVLRHPQPGA VELAAKHCRR PVINAGDGVG
2060 2070 2080 2090 2100
EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS
2110 2120 2130 2140 2150
LRYVAPPSLR MPPSVRDFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE
2160 2170 2180 2190 2200
RFGSVQEYEA CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR
2210 2220
AAYFRQAENG MYIRMALLAT VLGRF
Length:2,225
Mass (Da):243,238
Last modified:July 1, 2008 - v1
Checksum:iE7E606A0F650ABB4
GO
Isoform 2 (identifier: B2RQC6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1962-2032: Missing.

Show »
Length:2,154
Mass (Da):235,851
Checksum:iA83FA6E22929070C
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0539121962 – 2032Missing in isoform 2. 1 PublicationAdd BLAST71

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC109608 Genomic DNA No translation available.
CH466524 Genomic DNA Translation: EDL37329.1
BC137856 mRNA Translation: AAI37857.1
BC144972 mRNA Translation: AAI44973.1
CCDSiCCDS19171.1 [B2RQC6-1]
CCDS80246.1 [B2RQC6-2]
RefSeqiNP_001276451.1, NM_001289522.1 [B2RQC6-2]
NP_076014.1, NM_023525.2 [B2RQC6-1]
UniGeneiMm.305535

Genome annotation databases

EnsembliENSMUST00000013773; ENSMUSP00000013773; ENSMUSG00000013629 [B2RQC6-1]
ENSMUST00000201182; ENSMUSP00000144684; ENSMUSG00000013629 [B2RQC6-2]
GeneIDi69719
KEGGimmu:69719
UCSCiuc008wwz.2 mouse [B2RQC6-1]
uc012duk.2 mouse [B2RQC6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPYR1_MOUSE
AccessioniPrimary (citable) accession number: B2RQC6
Secondary accession number(s): B7ZN27
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 19, 2014
Last sequence update: July 1, 2008
Last modified: May 23, 2018
This is version 104 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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