CAD
CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase; alias GATD4) is a multifunctional protein that carries the first three enzymatic activities of the de novo pyrimidine pathway. Its activity is regulated by the MAPK cascade, linking mitogenic signalling to nucleotide synthesis. Browse Assay Genie's current range of CAD research reagents below, or read on for the biology behind the target.
CAD is a single polypeptide that encodes the first three enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase function proceeds in two steps. A glutamine-dependent amidotransferase (GATase) activity binds and cleaves glutamine to produce ammonia, and an ammonium-dependent carbamoyl phosphate synthetase then reacts that ammonia with hydrogencarbonate and ATP to form carbamoyl phosphate.
The carbamoyl phosphate made by CAD is sequestered and channelled to the ATCase active site, where ATCase catalyses the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the final step performed by this protein, DHOase catalyses the cyclisation of carbamoyl aspartate to dihydroorotate. Together these reactions cover the first three enzymes of the six-step pyrimidine biosynthesis pathway. The C-terminal section of the CAD protein belongs to the aspartate/ornithine carbamoyltransferase superfamily, ATCase family. HGNC places the CAD gene in the glutamine amidotransferase class 1 domain containing, ATP-grasp fold containing and carbamoyl-phosphate synthetases gene groups. UniProt reports the protein in the cytoplasm and the nucleus, and the mouse ortholog is named Cad.
De novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. NCBI Gene notes that CAD is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of MAPK signalling and de novo pyrimidine nucleotide biosynthesis. The gene undergoes alternative splicing, producing multiple transcript variants that encode different isoforms. GATD4 is a recognised alternative symbol for the gene.
CAD performs the first three steps of de novo pyrimidine biosynthesis, making it a central subject in studies of how cells build pyrimidine nucleotides.
Mammalian cells need de novo pyrimidine synthesis to proliferate, so CAD is relevant to work on how nucleotide supply supports cell growth.
Regulation of CAD by the MAPK cascade provides a direct link between mitogenic signalling and nucleotide biosynthesis.
Glutamine cleavage, carbamoyl phosphate formation and substrate channelling to the ATCase site make CAD a model for coordinated multi-step catalysis.
CAD is a trifunctional protein that catalyses the first three reactions of de novo pyrimidine biosynthesis. It forms carbamoyl phosphate from glutamine, hydrogencarbonate and ATP, converts it with L-aspartate to carbamoyl-L-aspartate, and then cyclises that product to dihydroorotate.
The HGNC full name is carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, and UniProt lists the protein as Multifunctional protein CAD. GATD4 is an alias. Alternative splicing of the CAD gene gives multiple transcript variants that encode different isoforms.
The mouse ortholog is called Cad, so the gene can be studied in mouse models; check the datasheet of any product for its validated reactivity. In mammalian cells the protein is regulated by the MAPK cascade, connecting growth signalling to pyrimidine synthesis.
Other pyrimidine and nucleotide-metabolism enzymes and MAPK pathway proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P27708; product specifications from Assay Genie datasheets.