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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]
CAD (Carbamoyl-Phosphate Synthetase 2, Aspartate Transcarbamylase, And Dihydroorotase) is a Protein Coding gene. Diseases associated with CAD include Epileptic Encephalopathy, Early Infantile, 50 and Cervical Polyp. Among its related pathways are superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis and MAPK Signaling: Mitogens. Gene Ontology (GO) annotations related to this gene include identical protein binding and enzyme binding. An important paralog of this gene is CPS1.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0003824 | catalytic activity | IEA | -- |
GO:0004070 | aspartate carbamoyltransferase activity | IEA,ISS | -- |
GO:0004088 | carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity | IEA,ISS | -- |
GO:0004151 | dihydroorotase activity | IBA,ISS | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA,IDA | 15890648 |
GO:0005654 | nucleoplasm | IDA | -- |
GO:0005737 | cytoplasm | IBA | 21873635 |
GO:0005829 | cytosol | IEA,TAS | -- |
GO:0016020 | membrane | HDA | 19946888 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Metabolism of nucleotides |
.01
|
|
2 | Metabolism |
.40
|
|
3 | superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis | ||
4 | DNA Damage | ||
5 | Glucose / Energy Metabolism |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001889 | liver development | IEA | -- |
GO:0006207 | 'de novo' pyrimidine nucleobase biosynthetic process | IEA,ISS | -- |
GO:0006221 | pyrimidine nucleotide biosynthetic process | IEA | -- |
GO:0006228 | UTP biosynthetic process | IBA | 21873635 |
GO:0006520 | cellular amino acid metabolic process | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Aspartic acid | Approved | Nutra | Enzyme, substrate | 182 | ||
L-Glutamine | Approved, Investigational | Nutra | Agonist, Full agonist, Enzyme, substrate | 0 | ||
Ammonia | Approved | Pharma | 0 | |||
Famotidine | Approved | Pharma | Histamine H2-receptor antagonist | 82 | ||
Phosphoric acid | Approved | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
Carbamoyl phosphate |
|
590-55-6 | ||||
4,5-Dihydroorotic acid |
|
155-54-4 |
|
|||
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
Carbonic acid |
|
71-52-3, 463-79-6 |
|
|||
L-Dihydroorotic acid |
|
5988-19-2 |
|
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: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CAD 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CAD 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CAD 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CAD 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Cad 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Cad 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | CAD 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | CAD 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | CAD 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | cad 30 |
|
||
Str.435 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.24787 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | cad 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | r 30 31 32 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP000300 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | pyr-1 30 31 |
|
OneToOne | |
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_ACR263C 30 |
|
||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0E15357g 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | URA2 30 31 33 |
|
OneToMany | |
Bread mold (Neurospora crassa) |
Ascomycetes | NCU08287 30 |
|
||
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | ura1 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.4454 31 |
|
OneToOne | |
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.9135 30 |
|
SNP ID | Clinical significance and condition | Chr 02 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
203466 | Pathogenic: Epileptic encephalopathy, early infantile, 50 | 27,242,098(+) | G/A | MISSENSE_VARIANT | |
654451 | Uncertain Significance: not provided | 27,238,177(+) | G/A | MISSENSE_VARIANT | |
708760 | Likely Benign: not provided | 27,239,136(+) | C/T | SYNONYMOUS_VARIANT | |
710412 | Benign: not provided | 27,233,482(+) | C/T | SYNONYMOUS_VARIANT | |
710841 | Likely Benign: not provided | 27,232,646(+) | C/T | SYNONYMOUS_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
epileptic encephalopathy, early infantile, 50 |
|
|
cervical polyp |
|
|