The human Rad9 checkpoint protein is a subunit of the heterotrimeric Rad9-Rad1-Hus1 (9-1-1) complex that plays a role as a damage sensor in the DNA damage checkpoint response. Rad9 has been found to interact with several other proteins outside the context of the 9-1-1 complex with no obvious checkpoint functions. During our studies on the 9-1-1 complex, we found that Rad9 immunoprecipitates contained a 240 kDa protein that was identified as carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD), a multienzymatic protein required for the de novo synthesis of pyrimidine nucleotides and cell growth. Further investigations revealed that only free Rad9, but not Rad9 within the 9-1-1 complex, bound to CAD. The rate-limiting step in de novo pyrimidine nucleotide synthesis is catalyzed by the carbamoyl phosphate synthetase II (CPSase) domain of CAD. We find that Rad9 binds to the CPSase domain, and, moreover, this binding results in a 2-fold stimulation of the CPSase activity of CAD. Similar results were also obtained with an N-terminal Rad9 fragment. These findings suggest that Rad9 may play a role in ribonucleotide biosynthesis.
The chemical reactions and pathways resulting in the formation of pyrimidine nucleobases, 1,3-diazine, organic nitrogenous bases, beginning with the synthesis of a pyrimidine ring from simpler precursors.
The chemical reactions and pathways resulting in the formation of UMP, uridine monophosphate, starting with the synthesis of (S)-dihydroorotate from bicarbonate; UMP biosynthesis may either occur via reduction by quinone, NAD(+) or oxygen.
The chemical reactions and pathways resulting in the formation of carbamoyl phosphate, an intermediate in the urea cycle and other nitrogen compound metabolic pathways.
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a drug stimulus. A drug is a substance used in the diagnosis, treatment or prevention of a disease.
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus.
The chemical reactions and pathways involving a drug, a substance used in the diagnosis, treatment or prevention of a disease; as used here antibiotic substances (see antibiotic metabolism) are considered to be drugs, even if not used in medical or veterinary practice.
The process whose specific outcome is the progression of an embryo from its formation until the end of its embryonic life stage. The end of the embryonic stage is organism-specific. For example, for mammals, the process would begin with zygote formation and end with birth. For insects, the process would begin at zygote formation and end with larval hatching. For plant zygotic embryos, this would be from zygote formation to the end of seed dormancy. For plant vegetative embryos, this would be from the initial determination of the cell or group of cells to form an embryo until the point when the embryo becomes independent of the parent plant.
The set of physiological processes that allow an embryo or foetus to develop within the body of a female animal. It covers the time from fertilization of a female ovum by a male spermatozoon until birth.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amine stimulus. An amine is a compound formally derived from ammonia by replacing one, two or three hydrogen atoms by hydrocarbyl groups.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a caffeine stimulus. Caffeine is an alkaloid found in numerous plant species, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cortisol stimulus. Cortisol is the major natural glucocorticoid synthesized in the zona fasciculata of the adrenal cortex; it affects the metabolism of glucose, protein, and fats and has appreciable mineralocorticoid activity. It also regulates the immune system and affects many other functions.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a testosterone stimulus.
Binds 1 zinc ion per subunit (for dihydroorotase activity) (Potential).
CuratedUniProtKB
It is regulated in the following manner
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate is an activator while UMP is an inhibitor of the CPSase reaction.
Protein involved in the biosynthesis of pyrimidine, a nitrogenous heterocyclic base, e.g. uracil, thymine, cytosine and orotic acid. Pyrimidines are synthesized from carbamoyl phosphate and aspartate. Ribose-5-phosphate is then attached to yield pyrimidine ribonucleotides. Cytosine is found in both DNA and RNA. Uracil is found only in RNA. Thymine is normally found in DNA. Sometimes tRNA contains some thymine as well as uracil.
Enzyme which catalyzes hydrolysis reaction, i.e. the addition of the hydrogen and hydroxyl ions of water to a molecule with its consequent splitting into two or more simpler molecules.
Enzyme that catalyzes the joining of two molecules coupled with the breakdown of a pyrophosphate bond in ATP or a similar triphosphate. Sometimes the terms "synthase", "synthetase" or "carboxylase" are also used for this class of enzymes.
Enzyme whose activity is modified by the noncovalent binding of an allosteric effector at a site other than the active site. This binding mediates conformational changes, altering its catalytic or binding properties.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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