Trifunctional purine biosynthetic protein adenosine-3 (GART)
The protein contains 1010 amino acids for an estimated molecular weight of 107767 Da.
No function (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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:rs1804387 | |
| dbSNP:rs8788 | |
| dbSNP:rs35927582 | |
| dbSNP:rs34588874 | |
| dbSNP:rs8971 |
Biological Process
'de novo' IMP biosynthetic process
Adenine biosynthetic process
Brainstem development
Cerebellum development
Cerebral cortex development
Glycine metabolic process
Purine nucleobase biosynthetic process
Purine nucleotide biosynthetic process
Purine ribonucleoside monophosphate biosynthetic process
Response to inorganic substance
Response to organic substance
Tetrahydrofolate biosynthetic process
The reference OMIM entry for this protein is 138440
Phosphoribosylglycinamide formyltransferase/phosphoribosylglycinamide synthetase/phosphoribosylaminoimidazole synthetase; gart glycinamide phosphoribosyltransferase, included
Glycinamide ribonucleotide synthetase, included; gars, included
Glycina
DESCRIPTION
The human GARS-AIRS-GART locus encodes 3 of the 10 enzymatic steps necessary for the conversion of phosphoribosyl pyrophosphate to inosine monophosphate by the de novo purine pathway. The 3 enzyme activities are encoded in a linear, nonoverlapping fashion on the GARS-AIRS-GART mRNA. Starting at the 5-prime end of the cDNA, the 3 enzyme activities are glycinamide ribonucleotide synthetase (GARS, EC 6.3.4.13), aminoimidazole ribonucleotide synthetase (AIRS, EC 6.3.3.1), and glycinamide ribonucleotide formyltransferase (GART, EC 2.1.2.2). These enzymatic activities catalyze the second, fifth, and third step of the de novo purine pathway, respectively. The fourth enzyme in the pathway, phosphoribosylformylglycineamide amidotransferase (FGARAT; 602133), is encoded by a gene on chromosome 17 (summary by Brodsky et al., 1997). Glutamine phosphoribosylpyrophosphate amidotransferase, encoded by the PPAT gene (172450), catalyzes the first step.CLONING
Glycine amide phosphoribosyl synthetase (EC 6.3.4.13) was identified by Patterson (1974) through an auxotrophic mutant (Ade-C). The enzyme is the second in the pathway of de novo purine biosynthesis. Schild et al. (1990) used functional complementation of mutation in yeast to isolate a human cDNA encoding the GART gene. Using yeast artificial chromosomes (YACs), Gnirke et al. (1991) cloned the human GART gene. Brodsky et al. (1997) generated monoclonal and/or polyclonal antibodies specific to each of the enzymatic domains of the trifunctional protein encoded by the GARS-AIRS-GART gene. Using these antibodies on Western blots of Chinese hamster ovary (CHO) cells transfected with the gene, they showed that the gene in fact encodes not only the trifunctional protein of 110 kD, but also a monofunctional GARS protein of 50 kD. This C terminal-truncated human GARS protein is produced by alternative splicing resulting in the use of a polyadenylation site in the intron between the terminal GARS and the first AIRS exons. The expression of both the GARS and GARS-AIRS-GART proteins is regulated during development of the human cerebellum, while the expression of FGARAT appears to be constitutive. All 3 proteins were found to be expressed at high levels during normal prenatal development of the cerebellum, while the GARS and GARS-AIRS-GART proteins become undetectable in the cerebellum shortly after birth. In contrast, both of these proteins continued to be expressed during the postnatal development of the cerebellum in individuals with Down syndrome.GENE FUNCTION
Patterson et al. (1980) stated that the elevation of serum purine levels observed in patients with Down syndrome (190685) may be related to the location of the gene for this multifunctional enzyme on chromosome 21. A third enzyme function, glycinamide phosphoribosyltransferase, or GART (EC 2.1.2.2), was the first to be discovered, in Drosophila. Hence, the whole is often referred to by this part--GART. In vertebrates, all 3 enzyme activities--GARS, GART, and PAIS--are on 1 polypeptide. There is at least 1 hamster cell line deficient in all 3 enzyme functions (Patterson, 1986). The GARS locus codes for a multifunctional enzyme which is conserved at least from Drosophila (O'Hare, 1986). It is a 'housekeeping' gene that is presumably expressed in all dividing cells.GENE STRUCTURE
Slavov et al. (2000) determined that the GART gene contains 21 exons spanning 35 kb.MAPPING
In studies of h ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 138440 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).