DCTPP1

Official Full Name

dCTP pyrophosphatase 1

Organism

Homo sapiens

GeneID

79077

Background

The protein encoded by this gene is dCTP pyrophosphatase, which converts dCTP to dCMP and inorganic pyrophosphate. The encoded protein also displays weak activity against dTTP and dATP, but none against dGTP. This protein may be responsible for eliminating excess dCTP after DNA synthesis and may prevent overmethylation of CpG islands. Three transcript variants, one protein-coding and the other two non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

Synonyms

CDA03; RS21C6; XTP3TPA;

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Detailed Information

The deoxycytidine triphosphatase pyrophosphatase 1 (Dctpp1) gene is a crucial enzyme involved in various cellular processes, including nucleotide metabolism, DNA replication, and cell signaling. The Dctpp1 enzyme is highly conserved across various species, indicating its essential role in biological processes.

Structure And Function of Dctpp1

The Dctpp1 gene encodes for an enzyme that belongs to the pyrophosphatase family, which is responsible for removing the terminal pyrophosphate group from various nucleotides. In particular, Dctpp1 is known to hydrolyze deoxycytidine triphosphate (dCTP) to deoxycytidine monophosphate (dCMP) and inorganic pyrophosphate. The structure of Dctpp1 enzyme has been identified, which reveals a classic Rossmann-fold domain and a catalytic center containing a highly conserved Asp-Glu-His-Asp (DEHD) motif. This motif is responsible for binding the substrate and facilitating the hydrolysis reaction.

The function of Dctpp1 is to regulate the cellular levels of deoxyribonucleotides, which are essential for DNA replication and repair. The hydrolysis of dCTP to dCMP by Dctpp1 plays a significant role in the control of DNA synthesis, as dCMP is a poor substrate for DNA polymerases. Moreover, Dctpp1 has been shown to regulate the levels of deoxyuridine monophosphate (dUMP), which is an essential precursor for the synthesis of thymidine, a component of DNA.

Regulation And Expression of Dctpp1

The expression of Dctpp1 is regulated at multiple levels, including transcription, translation, and post-translational modification. Transcriptional regulation of Dctpp1 has been reported to be influenced by various transcription factors and chromatin remodeling complexes. For instance, the activity of Dctpp1 is upregulated by the transcription factor Sp1, which binds to the promoter region of the Dctpp1 gene. Additionally, Dctpp1 expression can be regulated by RNA processing and degradation, as well as by microRNAs (miRNAs).

Post-translational modifications such as phosphorylation, ubiquitination, and sumoylation also play a significant role in regulating the activity and stability of Dctpp1. Phosphorylation of Dctpp1 at specific sites can modulate its enzymatic activity and cellular localization. For example, the phosphorylation of Dctpp1 at Serine 521 by cyclin-dependent kinase 2 (CDK2) promotes its nuclear localization and enhances its enzymatic activity.

Dctpp1 in Diseases

Alterations in the expression and function of Dctpp1 have been associated with various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In cancer, Dctpp1 has been reported to be overexpressed, which contributes to the uncontrolled cell growth and proliferation observed in tumors. Inhibition of Dctpp1 has been shown to inhibit cancer cell growth and to sensitize cells to chemotherapy.

In cardiovascular diseases, Dctpp1 has been implicated in the pathogenesis of atherosclerosis and arrhythmias. For instance, Dctpp1 is upregulated in cardiomyocytes following myocardial infarction, which suggests a role in the remodeling of the heart. In neurodegenerative disorders such as Alzheimer's disease (AD), Dctpp1 has been reported to be downregulated, which may contribute to the abnormal deposition of amyloid-beta (Aβ) plaques observed in AD patients.

References:

Llona-Minguez, Sabin et al. "Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP Pyrophosphatase 1 Inhibitors." Journal of medicinal chemistry vol. 60,10 (2017): 4279-4292. doi:10.1021/acs.jmedchem.7b00182
Song, F-F et al. "Human dCTP pyrophosphatase 1 promotes breast cancer cell growth and stemness through the modulation on 5-methyl-dCTP metabolism and global hypomethylation." Oncogenesis vol. 4,6 e159. 15 Jun. 2015, doi:10.1038/oncsis.2015.10

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