Adenosine deaminase (ADA)
The protein contains 363 amino acids for an estimated molecular weight of 40764 Da.
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:8452534, PubMed:16670267). Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4 (PubMed:20959412). Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (PubMed:20959412). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (PubMed:23193172). Stimulates plasminogen activation (PubMed:15016824). Plays a role in male fertility (PubMed:21919946, PubMed:26166670). Plays a protective role in early postimplantation embryonic development (By similarity). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- 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.
- 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.
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Adenosine catabolic process
Aging
AMP catabolic process
Cell adhesion
DAMP catabolic process
DATP catabolic process
Deoxyadenosine catabolic process
Embryonic digestive tract development
Germinal center B cell differentiation
Histamine secretion
Hypoxanthine salvage
Inosine biosynthetic process
Liver development
Lung alveolus development
Negative regulation of adenosine receptor signaling pathway
Negative regulation of circadian sleep/wake cycle, non-REM sleep
Negative regulation of inflammatory response
Negative regulation of leukocyte migration
Negative regulation of mature B cell apoptotic process
Negative regulation of mucus secretion
Negative regulation of penile erection
Negative regulation of thymocyte apoptotic process
Peyer's patch development
Placenta development
Positive regulation of alpha-beta T cell differentiation
Positive regulation of B cell proliferation
Positive regulation of calcium-mediated signaling
Positive regulation of germinal center formation
Positive regulation of heart rate
Positive regulation of smooth muscle contraction
Positive regulation of T cell differentiation in thymus
Positive regulation of T cell receptor signaling pathway
Purine nucleotide salvage
Purine ribonucleoside monophosphate biosynthetic process
Purine-containing compound salvage
Regulation of cell-cell adhesion mediated by integrin
Response to drug
Response to hydrogen peroxide
Response to hypoxia
Response to morphine
Response to vitamin E
T cell activation
Trophectodermal cell differentiation
Xanthine biosynthetic process
The reference OMIM entry for this protein is 102700
Severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-negative, due to adenosine deaminase deficiency
Scid due to ada deficiency
Ada-scid
Scid due to ada deficiency, early-onset scid due to ada deficie
A number sign (#) is used with this entry because T cell-negative (T-), B cell-negative (B-), natural killer cell-negative (NK-) severe combined immunodeficiency (SCID) is caused by mutation in the adenosine deaminase gene (ADA; 608958). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive SCID, see 601457.
CLINICAL FEATURES
Inherited ADA deficiency causes a variable phenotypic spectrum, the most severe being SCID presenting in infancy and usually resulting in early death. Ten to 15% of patients have a 'delayed' clinical onset by age 6 to 24 months, and a smaller percentage of patients have 'later' onset, diagnosed from ages 4 years to adulthood, showing less severe infections and gradual immunologic deterioration. Finally, 'partial' ADA deficiency occurs in a subset of immunocompetent individuals who show decreased enzyme activity in erythrocytes, but retain substantial enzyme activity ranging from 5 to 80% of normal in leukocytes and other nucleated cells (Arredondo-Vega et al., 1994). ADA deficiency accounts for approximately 15% of all SCID cases and one-third of cases of autosomal recessive SCID (Hershfield, 2003). - Early Onset Giblett et al. (1972) reported 2 unrelated girls with impaired cellular immunity and absence of red cell adenosine deaminase activity. One child, aged 22 months, had recurrent respiratory infections, candidiasis, and marked lymphopenia from birth. The other, aged 3.5 years, was allegedly normal in the first 2 years of life. Mild upper respiratory infections began at age 24 months and progressed to severe pulmonary insufficiency and hepatosplenomegaly by age 30 months. The parents of the first child were related and the second child had a sister who died as a result of a major immunologic defect (Hong et al., 1970). The finding that both pairs of parents had an intermediate level of red cell ADA supported recessive inheritance; the parents of the first child had about a 50% level of normal, whereas the parents of the second child had about a 66% level. Parkman et al. (1975) reported 3 affected infants from 2 families with SCID due to ADA deficiency inherited in an autosomal recessive pattern. None of the infants had detectable erythrocyte ADA activity. Two infants had successful bone marrow transplantation with restoration of normal cellular and humoral immunity, but erythrocytic ADA deficiency persisted. Reporting on a workshop on SCID due to ADA deficiency, Meuwissen et al. (1975) noted that the phenotype is transmitted as an autosomal recessive disorder. Some patients had characteristic skeletal abnormalities, and all had thymic involution with Hassall's corpuscles and differentiated germinal epithelium. Hershfield (2003) stated that red cell 2-prime-deoxyadenosine triphosphate (dATP; dAXP), a substrate of adenosine deaminase, is elevated by 30-fold to greater than 1,500-fold in SCID patients. - Delayed or Late Onset Santisteban et al. (1993) reported 7 patients with 'delayed' or 'late' onset of SCID due to ADA deficiency. Three of these patients had onset of symptoms at ages 9, 12, and 12 months, respectively, although diagnosis of ADA deficiency was not made until ages 14 months, 2, and 3 years, respectively. Four patients were relatively asymptomatic until ages 2 to 5 years, when recurrent respiratory infections became prominent. ADA activity in cultured T cells and deoxyadenosine nucleotide levels in red cells in all 7 patients were intermedi ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: OMIM entry 102700 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).