Adenylosuccinate lyase (ADSL)
The protein contains 484 amino acids for an estimated molecular weight of 54889 Da.
Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate. (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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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Biological Process
'de novo' AMP biosynthetic process
'de novo' IMP biosynthetic process
Aerobic respiration
AMP biosynthetic process
Metabolic process
Nucleobase-containing small molecule metabolic process
Protein tetramerization
Purine nucleobase metabolic process
Purine nucleotide biosynthetic process
Purine ribonucleoside monophosphate biosynthetic process
Response to hypoxia
Response to muscle activity
Response to nutrient
Response to starvation
Small molecule metabolic process
The reference OMIM entry for this protein is 103050
Adenylosuccinase deficiency
Adenylosuccinate lyase deficiency
Adsl deficiency
A number sign (#) is used with this entry because adenylosuccinase deficiency is caused by mutation in the gene encoding adenylosuccinate lyase (ADSL; 608222).
CLINICAL FEATURES
In 3 children with severe psychomotor delay and autism, Jaeken and Van den Berghe (1984) found succinyladenosine and succinylaminoimidazole carboxamide (SAICA) ribotide in the body fluids. Concentrations of both compounds were about 100 micromol/l in CSF, between 5 and 10 micromol/l in plasma, and in the millimol/l range in urine. Normally these compounds are not found in blood and CSF but may be detected in trace amounts in urine. The authors noted that the compounds are dephosphorylated derivatives of the intracellular metabolites adenylosuccinate and succinylaminoimidazole carboxamide ribotide, the 2 substrates of adenylosuccinase (adenylosuccinate lyase). Assays of the enzyme in 1 patient showed marked reduction of activity in liver and absence of activity in the kidney. Two of the 3 affected children were brother and sister, offspring of related Moroccan parents. The authors suggested that adenylosuccinase deficiency is a specific autosomal recessive cause of autism. Jaeken et al. (1988) presented clinical and biochemical data on 8 children with adenylosuccinase deficiency. Seven of the 8 children showed severe psychomotor retardation. Epilepsy was documented in 5, autistic features in 3, and growth retardation associated with muscular wasting in a brother and sister. One female patient was strikingly less retarded mentally and had only mild psychomotor retardation. In this patient, the ratio of the 2 metabolites in body fluids was quite different from that in the severely retarded patients, showing an approximately 5-fold excess of succinyladenosine. In addition, adenylosuccinase activity in fibroblasts was only about 6% of normal, whereas it was about 40% of normal in 6 severely retarded patients. At least 2 of the patients from separate families were the offspring of consanguineous parents. Jaeken et al. (1992) described a patient with an intermediate phenotypic severity resulting from adenylosuccinase deficiency. Chemical findings in the patient supported the impression that there is an inverse relationship between the degree of clinical involvement and the excess of succinyladenosine over SAICA riboside. Jaeken et al. (1992) concluded that SAICA riboside may be the offending compound that interferes with neurofunction and that succinyladenosine may protect against its effects. In Prague, Sebesta et al. (1997) screened urine samples from more than 2,000 children with unexplained neurologic disease. Using thin-layer chromatography, they identified 2 boys and 3 girls in 4 kindreds with adenylosuccinase deficiency. Two of the 4 kindreds were of Gypsy origin. Two boys were diagnosed at ages 2 and 5 years and 3 girls were diagnosed at ages 9 months, 3 years, and 6 years. The onset of the disease ranged from the fourteenth day to 6 months. Two sibs exhibited a less severe clinical picture and identical clinical course. They came to attention at the first year of life when psychomotor retardation developed. Neurologic examination showed hypotonia and hyperactivity. All 3 of the other patients exhibited severe psychomotor retardation in early infancy. Whereas most cases of adenylosuccinase deficiency had been detected by metabolic screening for severe psychomotor retardation, Maaswinkel-Mooij et al. (1997) described an infant who manifested generaliz ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 103050 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed