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Aliases for CAD Gene

Aliases for CAD Gene

  • Carbamoyl-Phosphate Synthetase 2, Aspartate Transcarbamylase, And Dihydroorotase 2 3
  • EC 63
  • EC 63
  • EC 63
  • EC 6.3.5 63

External Ids for CAD Gene

Previous GeneCards Identifiers for CAD Gene

  • GC02P027361
  • GC02P027532
  • GC02P027414
  • GC02P027351
  • GC02P027440
  • GC02P027181

Summaries for CAD Gene

Entrez Gene Summary for CAD Gene

  • The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. [provided by RefSeq, Jul 2008]

GeneCards Summary for CAD Gene

CAD (Carbamoyl-Phosphate Synthetase 2, Aspartate Transcarbamylase, And Dihydroorotase) is a Protein Coding gene. Among its related pathways are Cell Cycle / Checkpoint Control and Metabolism. GO annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is CPS1.

UniProtKB/Swiss-Prot for CAD Gene

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

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CAD Gene

Genomics for CAD Gene

Regulatory Elements for CAD Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for CAD Gene

27,217,390 bp from pter
27,243,943 bp from pter
26,554 bases
Plus strand

Genomic View for CAD Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for CAD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CAD Gene

Proteins for CAD Gene

  • Protein details for CAD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    CAD protein
    Protein Accession:
    Secondary Accessions:
    • D6W552
    • Q6P0Q0
    • Q96CK3

    Protein attributes for CAD Gene

    2225 amino acids
    Molecular mass:
    242984 Da
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 3 Zn(2+) ions per subunit (for dihydroorotase activity).;
    Quaternary structure:
    • Homohexamer.
    • GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC

    Three dimensional structures from OCA and Proteopedia for CAD Gene

neXtProt entry for CAD Gene

Proteomics data for CAD Gene at MOPED

Post-translational modifications for CAD Gene

  • 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.
  • Ubiquitination at Lys165, Lys186, Lys490, Lys696, Lys739, Lys747, Lys778, Lys1119, Lys1313, and Lys1411
  • Modification sites at PhosphoSitePlus

Other Protein References for CAD Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for CAD (CAD)

Domains for CAD Gene

Suggested Antigen Peptide Sequences for CAD Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Contains 2 ATP-grasp domains.
  • In the central section; belongs to the DHOase family.
  • Contains 2 ATP-grasp domains.
  • Contains 1 glutamine amidotransferase type-1 domain.
  • In the central section; belongs to the DHOase family.
genes like me logo Genes that share domains with CAD: view

No data available for Gene Families for CAD Gene

Function for CAD Gene

Molecular function for CAD Gene

GENATLAS Biochemistry:
pyrimidine de novo biosynthesis,multifunctional polypeptide,200kDa (see CPS2,ASTC,DHO),putative up-regulated c-Myc target gene,DNA metabolism
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=28 uM for dihydroorotate {ECO:0000269 PubMed:24332717}; KM=241 uM for N-carbamoyl-L-aspartate {ECO:0000269 PubMed:24332717};
UniProtKB/Swiss-Prot CatalyticActivity:
2 ATP + L-glutamine + HCO(3)(-) + H(2)O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate.
UniProtKB/Swiss-Prot CatalyticActivity:
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate.
UniProtKB/Swiss-Prot CatalyticActivity:
(S)-dihydroorotate + H(2)O = N-carbamoyl-L-aspartate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction.
UniProtKB/Swiss-Prot Function:
This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
UniProtKB/Swiss-Prot Induction:
Transcriptionally repressed following hypoxia by HIF1A.

Enzyme Numbers (IUBMB) for CAD Gene

Gene Ontology (GO) - Molecular Function for CAD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity --
GO:0004070 aspartate carbamoyltransferase activity TAS --
GO:0004087 carbamoyl-phosphate synthase (ammonia) activity IBA --
GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity TAS --
GO:0004151 dihydroorotase activity TAS --
genes like me logo Genes that share ontologies with CAD: view
genes like me logo Genes that share phenotypes with CAD: view

Animal Model Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for CAD Gene

Localization for CAD Gene

Subcellular locations from UniProtKB/Swiss-Prot for CAD Gene

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

Subcellular locations from

Jensen Localization Image for CAD Gene COMPARTMENTS Subcellular localization image for CAD gene
Compartment Confidence
cytosol 4
nucleus 4
endoplasmic reticulum 1
golgi apparatus 1
mitochondrion 1
peroxisome 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for CAD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA --
GO:0016020 membrane IDA 19946888
genes like me logo Genes that share ontologies with CAD: view

Pathways for CAD Gene

genes like me logo Genes that share pathways with CAD: view

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

UniProtKB/Swiss-Prot P27708-PYR1_HUMAN

  • Pathway: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3
  • Pathway: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3
  • Pathway: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3

Gene Ontology (GO) - Biological Process for CAD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000050 urea cycle IBA --
GO:0001889 liver development IEA --
GO:0006206 pyrimidine nucleobase metabolic process TAS --
GO:0006207 de novo pyrimidine nucleobase biosynthetic process ISS --
GO:0006228 UTP biosynthetic process IEA --
genes like me logo Genes that share ontologies with CAD: view

Drugs for CAD Gene

(3) Drugbank Compounds for CAD Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
  • (2S)-2-amino-4-carbamoylbutanoic acid
56-85-9 Enzyme substrate approved, investigational, nutraceutical
L-Aspartic Acid
  • (S)-2-aminobutanedioic acid
56-84-8 5960 Target approved, nutraceutical
N-(phosphonacetyl)-L-aspartic acid
51321-79-0 46936683 Target experimental

(17) HMDB Compounds for CAD Gene

Compound Synonyms Cas Number PubMed IDs
4,5-Dihydroorotic acid
  • (+)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate
Adenosine triphosphate
  • 5'-(Tetrahydrogen triphosphate) Adenosine
  • Adenosindiphosphorsaeure
  • Ammonia anhydrous
Carbamoyl phosphate
  • Carbamic acid monoanhydride with phosphorate

(21) Novoseek inferred chemical compound relationships for CAD Gene

Compound -log(P) Hits PubMed IDs
carbamoyl phosphate 91.8 21
n-phosphonacetyl-l-aspartate 90.5 10
carbamoyl-aspartate 89.8 4
phosphonoacetamide 89.6 3
dihydroorotate 89.1 9
genes like me logo Genes that share compounds with CAD: view

Transcripts for CAD Gene

Unigene Clusters for CAD Gene

Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for CAD Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18 ^ 19a · 19b ^ 20 ^ 21 ^
SP1: -

ExUns: 22 ^ 23 ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28 ^ 29 ^ 30a · 30b ^ 31 ^ 32 ^ 33a · 33b ^ 34 ^ 35a · 35b · 35c ^ 36 ^ 37 ^ 38 ^ 39a · 39b ^ 40a · 40b ^
SP1: - - - -
SP2: - - - -
SP3: -
SP4: - - - - - - - - - - - -

ExUns: 41a · 41b · 41c · 41d · 41e · 41f ^ 42 ^ 43a · 43b ^ 44 ^ 45 ^ 46a · 46b
SP5: - - - - -

Relevant External Links for CAD Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CAD Gene

mRNA expression in normal human tissues for CAD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues for CAD Gene

This gene is overexpressed in Peripheral blood mononuclear cells (13.4), Breast (7.4), and Lymph node (6.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for CAD Gene

SOURCE GeneReport for Unigene cluster for CAD Gene Hs.377010

genes like me logo Genes that share expressions with CAD: view

Expression partners for CAD Gene

* - Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for CAD Gene

Orthologs for CAD Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CAD Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia CAD 35
  • 90.32 (n)
  • 97.12 (a)
CAD 36
  • 96 (a)
(Canis familiaris)
Mammalia CAD 35
  • 90.79 (n)
  • 97.44 (a)
CAD 36
  • 97 (a)
(Mus musculus)
Mammalia Cad 35
  • 88.7 (n)
  • 95.37 (a)
Cad 16
Cad 36
  • 95 (a)
(Pan troglodytes)
Mammalia CAD 35
  • 99.76 (n)
  • 99.91 (a)
CAD 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Cad 35
  • 88.28 (n)
  • 94.97 (a)
(Monodelphis domestica)
Mammalia CAD 36
  • 93 (a)
(Ornithorhynchus anatinus)
Mammalia CAD 36
  • 77 (a)
(Gallus gallus)
Aves CAD 35
  • 75.3 (n)
  • 81.49 (a)
CAD 36
  • 81 (a)
(Anolis carolinensis)
Reptilia CAD 36
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia cad 35
  • 74.08 (n)
  • 80.94 (a)
Str.435 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.24787 35
(Danio rerio)
Actinopterygii cad 35
  • 70.6 (n)
  • 78.19 (a)
cad 36
  • 77 (a)
fruit fly
(Drosophila melanogaster)
Insecta r 37
  • 52 (a)
r 35
  • 63.52 (n)
  • 65.73 (a)
r 36
  • 63 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000300 35
  • 43.16 (n)
  • 35.05 (a)
(Caenorhabditis elegans)
Secernentea pyr-1 35
  • 56.97 (n)
  • 59.34 (a)
pyr-1 36
  • 57 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR263C 35
  • 54.73 (n)
  • 52.75 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E15357g 35
  • 52.83 (n)
  • 53.48 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes URA2 35
  • 52.72 (n)
  • 53.47 (a)
URA2 36
  • 50 (a)
CPA2 38
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9135 35
bread mold
(Neurospora crassa)
Ascomycetes NCU08287 35
  • 58.79 (n)
  • 58.63 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes ura1 35
  • 52.79 (n)
  • 53.51 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.4454 36
  • 38 (a)
Species with no ortholog for CAD:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CAD Gene

Gene Tree for CAD (if available)
Gene Tree for CAD (if available)

Paralogs for CAD Gene

Paralogs for CAD Gene

(1) SIMAP similar genes for CAD Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with CAD: view

Variants for CAD Gene

Sequence variations from dbSNP and Humsavar for CAD Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs724310 -- 27,218,687(+) TTCCT(A/G)CAGTG intron-variant
rs724311 -- 27,218,777(+) CATAT(A/G)GTAAT intron-variant
rs1056891 -- 27,236,427(+) CTCTC(C/T)TCCTT synonymous-codon, reference
rs1141311 -- 27,237,520(+) TGACG(C/G)CCCTG reference, missense
rs1141312 -- 27,237,542(+) GCCCA(A/G)AAGCT synonymous-codon, reference

Structural Variations from Database of Genomic Variants (DGV) for CAD Gene

Variant ID Type Subtype PubMed ID
nsv833603 CNV Loss 17160897
nsv873754 CNV Loss 21882294
esv275571 CNV Loss 21479260

Relevant External Links for CAD Gene

HapMap Linkage Disequilibrium report

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CAD Gene

Disorders for CAD Gene

(3) Novoseek inferred disease relationships for CAD Gene

Disease -log(P) Hits PubMed IDs
fibrosarcoma 21.2 1
breast cancer 0 3
tumors 0 2

Relevant External Links for CAD

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with CAD: view

No data available for MalaCards , OMIM , UniProtKB/Swiss-Prot , University of Copenhagen DISEASES and Genatlas for CAD Gene

Publications for CAD Gene

  1. Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase- dihydroorotase in de Novo pyrimidine synthesis. (PMID: 8619816) Iwahana H. … Itakura M. (Biochem. Biophys. Res. Commun. 1996) 2 3 4 23
  2. Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha. (PMID: 16155188) Chen K.F. … Tsai S.J. (Nucleic Acids Res. 2005) 3 4 23
  3. Organization and nucleotide sequence of the 3' end of the human CAD gene. (PMID: 1979741) Davidson J.N. … Chen K.C. (DNA Cell Biol. 1990) 3 4 23
  4. Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD. (PMID: 15890648) Sigoillot F.D. … Guy H.I. (J. Biol. Chem. 2005) 3 4 23
  5. Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17beta-estradiol in breast cancer cells. (PMID: 12746293) Khan S. … Safe S. (Endocrinology 2003) 3 23

Products for CAD Gene

Sources for CAD Gene

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