CTPS1
CTPS1 (CTP synthase 1; also known as GATD5A and CTPS) is a cytosolic enzyme that catalyses the final, rate-defining step in de novo CTP synthesis, converting UTP to CTP. It also acts as a protein deamidase, linking nucleotide metabolism to innate immunity and DNA repair. Browse Assay Genie's current range of CTPS1 research reagents below, or read on for the biology behind the target.
CTPS1 is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. The enzyme catalyses the ATP-dependent amination of UTP to CTP, using either L-glutamine or ammonia as the nitrogen source. This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. CTPS1 activity is especially important for the proliferation of activated lymphocytes, which need additional CTP to meet the increased demand for DNA, RNA and lipid membrane biosynthesis.
Beyond nucleotide synthesis, the CTPS1 protein has a second activity as a protein deamidase, converting the side chain of specific asparagine residues to aspartate. In this role it acts as a negative regulator of innate immunity by deamidating Asn-85 of IRF3, which prevents IRF3 from binding DNA. It also promotes chromatin relaxation after DNA damage by deamidating Asn-76 and Asn-77 of histone H1. This promotes acetylation of histone H1 at Lys-75 (H1K75ac) and increases chromatin accessibility, which helps recruit DNA repair proteins. The localisation of CTPS1 to the cytosol, nucleus and chromosome is consistent with these functions.
The CTPS1 gene belongs to the CTP synthase family and to the glutamine amidotransferase class 1 domain containing group. Its previous name was simply CTP synthase. Alternative splicing produces multiple transcript variants. Loss of function of the CTPS1 gene has been associated with immunodeficiency, which reflects the dependence of the immune system on this enzyme. The mouse ortholog is Ctps1.
CTPS1 catalyses the de novo conversion of UTP to CTP, supplying a precursor for DNA, RNA and phospholipid synthesis.
CTPS1 activity is crucial for the proliferation of activated lymphocytes, and loss of function has been associated with immunodeficiency.
CTPS1 deamidates IRF3 at Asn-85, preventing DNA binding and acting as a negative regulator of innate immunity.
CTPS1 deamidates histone H1, promoting H1K75 acetylation and chromatin relaxation to facilitate recruitment of DNA repair proteins.
CTPS1 catalyses the ATP-dependent amination of UTP to CTP, using L-glutamine or ammonia as the nitrogen source, in de novo CTP synthesis. It also works as a protein deamidase, acting on IRF3 and histone H1, so it contributes to innate immune regulation and DNA damage responses.
CTPS1 is the approved HGNC symbol for CTP synthase 1. Aliases and previous symbols include GATD5A and CTPS, and the previous name was CTP synthase. UniProt lists it as P17812. Alternative splicing of the gene gives multiple transcript variants.
Loss of function of the CTPS1 gene has been associated with immunodeficiency, in line with its role in lymphocyte proliferation. The mouse has an ortholog, Ctps1. Check the datasheet of any product for its validated reactivity.
Pathway partners and related enzymes in nucleotide metabolism, innate immunity and DNA repair with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P17812; product specifications from Assay Genie datasheets.