CTP synthase 1 (CTPS1)
The protein contains 591 amino acids for an estimated molecular weight of 66690 Da.
This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs17856308 |
Biological Process
'de novo' CTP biosynthetic process
B cell proliferation
CTP biosynthetic process
Glutamine metabolic process
Nucleobase-containing compound metabolic process
Nucleobase-containing small molecule interconversion
Nucleobase-containing small molecule metabolic process
Pyrimidine nucleobase biosynthetic process
Response to drug
Small molecule metabolic process
T cell proliferation
The reference OMIM entry for this protein is 123860
Cytidine 5-prime triphosphate synthetase 1; ctps1
Ctps
Ctp synthetase
Ctp synthase
DESCRIPTION
The catalytic conversion of UTP to CTP is accomplished by the enzyme cytidine-5-prime-triphosphate synthetase (UTP:L-glutamine amido ligase; EC 6.3.4.2). The enzyme, encoded by the CTPS1 gene, is important in the biosynthesis of phospholipids and nucleic acids, and plays a key role in cell growth, development, and tumorigenesis (summary by Thomas et al., 1989).CLONING
Thomas et al. (1989) isolated a cDNA clone of the CTP synthetase gene from a rat liver cDNA library. It is a key regulatory enzyme in pyrimidine biosynthesis. These authors isolated both cDNA and genomic gene sequences from the rat and Chinese hamster. Yamauchi et al. (1990) cloned the CTPS gene and showed that the open reading frame encodes 591 amino acids that have a striking degree of similarity to the structural gene in E. coli.GENE FUNCTION
Martin et al. (2014) found that CTPS1 mRNA was comparable among different normal tissues, except for T cells in which CTPS1 expression was strongly upregulated after cell activation in response to T cell receptor (TCR) CD3 and CD28 costimulation. In lysates from resting nonactivated T cells, CTPS1 protein was almost undetectable.GENE STRUCTURE
Yamauchi et al. (1991) determined that the CTPS1 genomic sequence is distributed in 19 exons covering about 35 kb.MAPPING
Yamauchi et al. (1991) assigned the structural CTPS1 gene to chromosome 1p by study of a panel of human/rodent somatic cell hybrids and the CTPS cDNA. By a method of mapping that combines fluorescence in situ hybridization with replicated prometaphase R-bands (Takahashi et al., 1990), Takahashi et al. (1991) mapped the CTPS1 gene to chromosome 1p34.3-p34.1. By high-resolution banding analysis, they further narrowed the assignment to 1p34.1; see Yamauchi et al. (1991).MOLECULAR GENETICS
- Immunodeficiency 24 Martin et al. (2014) identified 5 families with 1 or 2 children who all presented with a severe form of combined deficiency of adaptive immunity (CID). The children had severe chronic viral infections, mostly caused by herpesviruses, as well as recurrent encapsulated bacterial infections (IMD24; 615897). All patients were homozygous for a splice site mutation in CTPS1 (123860.0001). CTPS1-deficient cells from 3 patients failed to sustain proliferative responses in response to activation by antigens, anti-CD3 antibody, or costimulation by anti-CD3 and anti-CD28 antibodies, as measured by 3-H-thymidine uptake and other methods. Uptakes of 3-H-uridine and 3-H-cytidine were also impaired in activated CTPS1-deficient T cells, suggesting that both RNA and DNA synthesis were affected. Defective proliferation of CTPS1-deficient T cells was associated with a lack of cell cycle progression, as most cells were arrested in the G1 phase. CTPS1 deficiency causes a defect in T-cell proliferation in response to TCR CD3 activation. Reconstitution experiments with wildtype CTPS1 or direct addition of CTP or its cytidine precursor fully restored proliferation upon CD3 stimulation and enabled cells to expand selectively. No such effect was detected in CTPS1-deficient cells transduced with an empty vector or in control cells transduced with the CTPS1-containing vector. Martin et al. (2014) also found that proliferation of B cells was dependent on CTPS1; however, CTPS1-deficient B cells preserved an intact capacity to expand upon transformation by EBV, and patients had normal immunoglobulin levels and/or eleva ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 123860 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed