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Aliases for CAD Gene

Aliases for CAD Gene

  • Carbamoyl-Phosphate Synthetase 2, Aspartate Transcarbamylase, And Dihydroorotase 2 3 5
  • Multifunctional Protein CAD 3
  • CAD Trifunctional Protein 3
  • EC 6.3.5.5 63
  • EC 2.1.3.2 63
  • EC 3.5.2.3 63
  • EC 6.3.5 63
  • CDG1Z 3

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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

GeneCards Summary for CAD Gene

CAD (Carbamoyl-Phosphate Synthetase 2, Aspartate Transcarbamylase, And Dihydroorotase) is a Protein Coding gene. Diseases associated with CAD include Congenital Disorder Of Glycosylation, Type Iz. Among its related pathways are Purine metabolism and Glucose / Energy Metabolism. GO annotations related to this gene include identical protein binding and enzyme binding. 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

Enhancers for CAD Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around CAD on UCSC Golden Path with GeneCards custom track

Promoters for CAD Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around CAD on UCSC Golden Path with GeneCards custom track

Genomic Location for CAD Gene

Chromosome:
2
Start:
27,217,390 bp from pter
End:
27,243,943 bp from pter
Size:
26,554 bases
Orientation:
Plus strand

Genomic View for CAD Gene

Genes around CAD on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CAD Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    P27708-PYR1_HUMAN
    Recommended name:
    CAD protein
    Protein Accession:
    P27708
    Secondary Accessions:
    • D6W552
    • Q6P0Q0
    • Q96CK3

    Protein attributes for CAD Gene

    Size:
    2225 amino acids
    Molecular mass:
    242984 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homohexamer.
    Miscellaneous:
    • GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC 6.3.5.5).

    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 Lys 165, Lys 186, Lys 490, Lys 696, Lys 739, Lys 747, Lys 778, Lys 1119, and Lys 1313
  • Modification sites at PhosphoSitePlus

Other Protein References for CAD Gene

Domains & Families for CAD Gene

Suggested Antigen Peptide Sequences for CAD Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P27708

UniProtKB/Swiss-Prot:

PYR1_HUMAN :
  • Contains 2 ATP-grasp domains.
  • In the central section; belongs to the DHOase family.
Domain:
  • Contains 2 ATP-grasp domains.
  • Contains 1 glutamine amidotransferase type-1 domain.
Family:
  • 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:0016812 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CAD: view
genes like me logo Genes that share phenotypes with CAD: view

Human Phenotype Ontology for CAD Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

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

COMPARTMENTS
Jensen Localization Image for CAD Gene COMPARTMENTS Subcellular localization image for CAD gene
Compartment Confidence
cytosol 5
extracellular 5
nucleus 5
plasma membrane 2
endoplasmic reticulum 1
golgi apparatus 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for CAD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0070062 extracellular exosome IDA 20458337
genes like me logo Genes that share ontologies with CAD: view

Pathways & Interactions for CAD Gene

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

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.

SIGNOR curated interactions for CAD Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CAD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006206 pyrimidine nucleobase metabolic process TAS --
GO:0006207 de novo pyrimidine nucleobase biosynthetic process IEA,ISS --
GO:0006520 cellular amino acid metabolic process IEA --
GO:0006541 glutamine metabolic process IEA,ISS --
GO:0007507 heart development IEA --
genes like me logo Genes that share ontologies with CAD: view

Drugs & Compounds for CAD Gene

(17) Drugs for CAD Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
L-Aspartic acid Approved Nutra Target NMDA agonist 0
L-Glutamine Approved, Investigational Nutra Full agonist, Agonist, Enzyme, substrate 0
Famotidine Approved Pharma Histamine H2-receptor antagonist 57
Adenosine triphosphate Approved Nutra 0
N-(phosphonacetyl)-L-aspartic acid Experimental Pharma Target 0

(21) Additional Compounds for CAD Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Carbamoyl phosphate
  • Carbamic acid monoanhydride with phosphorate
  • Carbamic acid monoanhydride with phosphoric acid
  • Carbamoyl-P
  • Carbamoyl-phosphate
  • Carbamoylphosphate
590-55-6
4,5-Dihydroorotic acid
  • (+)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate
  • (+)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylic acid
  • (R)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate
  • (R)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylic acid
  • (S)-2,6-dioxo-hexahydro-pyrimidine-4-carboxylate
155-54-4
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Ammonia
  • Ammonia anhydrous
  • Ammonia inhalant
  • Ammonia solution strong [usan]
  • Ammonia water
  • Ammoniak
7664-41-7
Carbonic acid
  • Acid of air
  • Aerial acid
  • Bisodium carbonate
  • Calcined
  • Carbonic acid sodium salt
463-79-6
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: -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:

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: - - - - - - - - - - - -
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:

ExUns: 41a · 41b · 41c · 41d · 41e · 41f ^ 42 ^ 43a · 43b ^ 44 ^ 45 ^ 46a · 46b
SP1:
SP2:
SP3:
SP4:
SP5: - - - - -
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:

Relevant External Links for CAD Gene

GeneLoc Exon Structure for
CAD
ECgene alternative splicing isoforms for
CAD

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 from HIPED 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 in normal tissues and cell lines 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 expression patterns with CAD: view

Protein tissue co-expression partners for CAD Gene

- Elite partner

Primer 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
cow
(Bos Taurus)
Mammalia CAD 35
  • 90.32 (n)
  • 97.12 (a)
CAD 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CAD 35
  • 90.79 (n)
  • 97.44 (a)
CAD 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cad 35
  • 88.7 (n)
  • 95.37 (a)
Cad 16
Cad 36
  • 95 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia CAD 35
  • 99.76 (n)
  • 99.91 (a)
CAD 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cad 35
  • 88.28 (n)
  • 94.97 (a)
oppossum
(Monodelphis domestica)
Mammalia CAD 36
  • 93 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CAD 36
  • 77 (a)
OneToOne
chicken
(Gallus gallus)
Aves CAD 35
  • 75.3 (n)
  • 81.49 (a)
CAD 36
  • 81 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CAD 36
  • 80 (a)
OneToOne
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
zebrafish
(Danio rerio)
Actinopterygii cad 35
  • 70.6 (n)
  • 78.19 (a)
cad 36
  • 77 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta r 37
  • 52 (a)
r 35
  • 63.52 (n)
  • 65.73 (a)
r 36
  • 63 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000300 35
  • 43.16 (n)
  • 35.05 (a)
worm
(Caenorhabditis elegans)
Secernentea pyr-1 35
  • 56.97 (n)
  • 59.34 (a)
pyr-1 36
  • 57 (a)
OneToOne
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)
OneToMany
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)
OneToOne
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

ENSEMBL:
Gene Tree for CAD (if available)
TreeFam:
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
VAR_035897 A colorectal cancer sample
VAR_035898 A colorectal cancer sample
VAR_073955 Congenital disorder of glycosylation 1Z (CDG1Z)
rs724310 -- 27,218,687(+) TTCCT(A/G)CAGTG intron-variant
rs724311 -- 27,218,777(+) CATAT(A/G)GTAAT intron-variant

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

Variation tolerance for CAD Gene

Residual Variation Intolerance Score: 0.0663% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.14; 51.51% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CAD Gene

Human Gene Mutation Database (HGMD)
CAD

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

Disorders for CAD Gene

MalaCards: The human disease database

(1) MalaCards diseases for CAD Gene - From: OMIM, ClinVar, and Swiss-Prot

Disorder Aliases PubMed IDs
congenital disorder of glycosylation, type iz
  • cdg1z
- elite association - COSMIC cancer census association via MalaCards
Search CAD in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PYR1_HUMAN
  • Congenital disorder of glycosylation 1Z (CDG1Z) [MIM:616457]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1Z patients show abnormal glycosylation of red blood cell proteins, but glycosylation of serum transferrin is normal. {ECO:0000269 PubMed:25678555}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CAD

Genetic Association Database (GAD)
CAD
Human Genome Epidemiology (HuGE) Navigator
CAD
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CAD
genes like me logo Genes that share disorders with CAD: view

No data available for 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 67
  2. Drugs, their targets and the nature and number of drug targets. (PMID: 17016423) Imming P. … Meyer A. (Nat Rev Drug Discov 2006) 25 26
  3. How many drug targets are there? (PMID: 17139284) Overington J.P. … Hopkins A.L. (Nat Rev Drug Discov 2006) 25 26
  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 23
  5. Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha. (PMID: 16155188) Chen K.F. … Tsai S.J. (Nucleic Acids Res. 2005) 3 23

Products for CAD Gene

Sources for CAD Gene

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