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Gene Review

ADA  -  adenosine deaminase

Homo sapiens

Synonyms: ADA1, Adenosine aminohydrolase, Adenosine deaminase
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Disease relevance of ADA


Psychiatry related information on ADA

  • Nitric oxide, adenosine deaminase, xanthine oxidase and superoxide dismutase in patients with panic disorder: alterations by antidepressant treatment [6].
  • Direct assessments of ADA catalytic activity in autistic individuals and unaffected siblings carrying ADA1/ADA1 vs ADA1/ADA2 genotypes may provide stronger evidence of ADA2 contributions to autistic disorder [7].
  • A specific correlation to drug addition and its duration was observed: LAS subjects who discontinued drug abuse (median addiction time: 3 years) presented ADA values (median = 13 U) that are lower than for addicts (median = 27.2 U; median addiction time = 7 years) and are close to those observed for asymptomatic HIV-I serum-positive group [8].
  • Association of adenosine deaminase polymorphism with mild mental retardation [9].
  • DESIGN AND METHODS: Serum neopterin concentration, and the chitotriosidase (ChT), angiotensin-converting enzyme (ACE) and adenosine deaminase (ADA) activities were determined in 30 patients with AD, in 19 patients with other types of dementia, and in 24 nonaffected controls [10].

High impact information on ADA


Chemical compound and disease context of ADA


Biological context of ADA


Anatomical context of ADA

  • ADA was coexpressed with CD26 on the Jurkat T cell lines, and an in vitro binding assay showed that the binding was through the extracellular domain of CD26 [1].
  • From colocalization studies, it is deduced that ADA colocalizing with adenosine receptors on dendritic cells interact with CD26 expressed on lymphocytes [14].
  • ADA activity was also increased after infection of a human ADA-deficient B-cell line [2].
  • Although NIH 3T3 cells infected with either construct produced human ADA activity, substantially greater levels were attained with DHFR*-SVADA [2].
  • In erythrocytes from healthy individuals, mean (SD) ADA activity was 5619 (2584) nmol/s per liter of packed cells [23].

Associations of ADA with chemical compounds

  • The deoxynucleoside kinases (deoxyguanosine, deoxyadenosine, and deoxycytidine kinases) paralleled the changes in ADA and TdT activity among the different T subsets [15].
  • On epithelia and lymphoid cells of humans, but not mice, ADA also occurs bound to the membrane glycoprotein CD26/dipeptidyl peptidase IV [19].
  • Mutating these residues to alanine increased dissociation rates 6-11-fold and the apparent dissociation constant K(D) for wild type human ADA from 17 to 112-160 nm, changing binding free energy by 1.1-1.3 kcal/mol [19].
  • It is associated with molecules of immunological importance such as the protein tyrosine phosphatase CD45 and adenosine deaminase (ADA) on the cell surface [24].
  • Among the 5 non-conserved residues within this segment, Arg-142 in human and Gln-142 in mouse ADA largely determined the capacity for stable binding to CD26 (Richard, E., Arredondo-Vega, F. X., Santisteban, I., Kelly, S. J., Patel, D. D., and Hershfield, M. S. (2000) J. Exp. Med. 192, 1223-1235) [19].

Physical interactions of ADA


Co-localisations of ADA

  • Introduction of the nucleotide substitution into an ADA 1 cDNA and transfection into monkey kidney (Cos) cells confirmed that the mutation resulted in expression of an enzyme that comigrated with the naturally occurring ADA 2 allozyme [29].
  • SDF-1alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present [30].

Regulatory relationships of ADA


Other interactions of ADA

  • Direct association of adenosine deaminase with a T cell activation antigen, CD26 [1].
  • A suspension of living lymphocytes is mixed with agarose sol containing the reagents for the detection of PNP or ADA activity on a glass slide [4].
  • Proinflammatory cytokines did not affect ADA1 activity or ADA mRNA expression in RA FLS [35].
  • Since ADA and Pg bind to CD26 at distinct but nearby sites, we investigated a possible interaction between these two proteins on the surface of 1-LN cells [25].
  • Increased ADA and decreased XO, SOD, and CAT activities were found in cancerous bladder tissues compared with those of cancer-free adjacent tissues and of control bladder tissues [36].

Analytical, diagnostic and therapeutic context of ADA


  1. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Kameoka, J., Tanaka, T., Nojima, Y., Schlossman, S.F., Morimoto, C. Science (1993) [Pubmed]
  2. Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. Williams, D.A., Orkin, S.H., Mulligan, R.C. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  3. Enzyme analysis of lymphoproliferative diseases: a useful addition to cell surface phenotyping. van de Griend, R.J., van der Reijden, H.J., Bolhuis, R.L., Melief, C.J., von dem Borne, A.E., Roos, D. Blood (1983) [Pubmed]
  4. Purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) activities examined cytochemically in unfixed lymphocytes of patients with lymphoproliferative disorders. Maeda, K., Ito, K., Yamaguchi, N. Blood (1981) [Pubmed]
  5. Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications. Hönig, M., Albert, M.H., Schulz, A., Sparber-Sauer, M., Schütz, C., Belohradsky, B., Güngör, T., Rojewski, M.T., Bode, H., Pannicke, U., Lippold, D., Schwarz, K., Debatin, K.M., Hershfield, M.S., Friedrich, W. Blood (2007) [Pubmed]
  6. Nitric oxide, adenosine deaminase, xanthine oxidase and superoxide dismutase in patients with panic disorder: alterations by antidepressant treatment. Herken, H., Akyol, O., Yilmaz, H.R., Tutkun, H., Savas, H.A., Ozen, M.E., Kalenderoglu, A., Gulec, M. Human psychopharmacology. (2006) [Pubmed]
  7. Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies. Persico, A.M., Militerni, R., Bravaccio, C., Schneider, C., Melmed, R., Trillo, S., Montecchi, F., Palermo, M.T., Pascucci, T., Puglisi-Allegra, S., Reichelt, K.L., Conciatori, M., Baldi, A., Keller, F. Am. J. Med. Genet. (2000) [Pubmed]
  8. Prognostic significance of adenosine deaminase determinations in subjects with the lymphoadenopathy syndrome. Casoli, C., Magnani, G., Scovassi, I., Bertazzoni, U., Starcich, R. J. Med. Virol. (1988) [Pubmed]
  9. Association of adenosine deaminase polymorphism with mild mental retardation. Saccucci, P., Arpino, C., Rizzo, R., Gagliano, A., Volzone, A., Lalli, C., Galasso, C., Curatolo, P. J. Child Neurol. (2006) [Pubmed]
  10. Serum markers of monocyte/macrophage activation in patients with Alzheimer's disease and other types of dementia. Casal, J.A., Robles, A., Tutor, J.C. Clin. Biochem. (2003) [Pubmed]
  11. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Buckley, R.H. Annu. Rev. Immunol. (2004) [Pubmed]
  12. Gene therapy of the immune system. Cournoyer, D., Caskey, C.T. Annu. Rev. Immunol. (1993) [Pubmed]
  13. Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency. Hirschhorn, R., Yang, D.R., Puck, J.M., Huie, M.L., Jiang, C.K., Kurlandsky, L.E. Nat. Genet. (1996) [Pubmed]
  14. CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse. Pacheco, R., Martinez-Navio, J.M., Lejeune, M., Climent, N., Oliva, H., Gatell, J.M., Gallart, T., Mallol, J., Lluis, C., Franco, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  15. Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes. Ma, D.D., Sylwestrowicz, T.A., Granger, S., Massaia, M., Franks, R., Janossy, G., Hoffbrand, A.V. J. Immunol. (1982) [Pubmed]
  16. The HIV-1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression. Blanco, J., Valenzuela, A., Herrera, C., Lluís, C., Hovanessian, A.G., Franco, R. FEBS Lett. (2000) [Pubmed]
  17. Serum adenosine deaminase activity and its isoenzyme pattern in women with normal pregnancies. Yoneyama, Y., Suzuki, S., Sawa, R., Otsubo, Y., Miura, A., Kuwabara, Y., Ishino, H., Kiyokawa, Y., Doi, D., Yoneyama, K., Araki, T. Arch. Gynecol. Obstet. (2003) [Pubmed]
  18. Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis. Durak, I., Ormeci, N., Akyol, O., Canbolat, O., Kavutçu, M., Bülbül, M. Dig. Dis. Sci. (1994) [Pubmed]
  19. Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV. Richard, E., Alam, S.M., Arredondo-Vega, F.X., Patel, D.D., Hershfield, M.S. J. Biol. Chem. (2002) [Pubmed]
  20. Specific binding of adenosine deaminase but not HIV-1 transactivator protein Tat to human CD26. Blanco, J., Marié, I., Callebaut, C., Jacotot, E., Krust, B., Hovanessian, A.G. Exp. Cell Res. (1996) [Pubmed]
  21. Adenosine deaminase and purine nucleoside phosphorylase in childhood lymphoblastic leukemia: relation with differentiation stage, in vitro drug resistance and clinical prognosis. Pieters, R., Huismans, D.R., Loonen, A.H., Peters, G.J., Hählen, K., van der Does-van den Berg, A., van Wering, E.R., Veerman, A.J. Leukemia (1992) [Pubmed]
  22. Evidence of selective interaction between adenosine deaminase and acid phosphatase polymorphisms in fetuses carried by diabetic women. Bottini, E., Gerlini, G., Lucarini, N., Amante, A., Gloria-Bottini, F. Hum. Genet. (1991) [Pubmed]
  23. Capillary electrophoresis in diagnosis and monitoring of adenosine deaminase deficiency. Carlucci, F., Tabucchi, A., Aiuti, A., Rosi, F., Floccari, F., Pagani, R., Marinello, E. Clin. Chem. (2003) [Pubmed]
  24. Dipeptidyl-peptidase IV/CD26 on T cells: analysis of an alternative T-cell activation pathway. von Bonin, A., Hühn, J., Fleischer, B. Immunol. Rev. (1998) [Pubmed]
  25. Cell surface adenosine deaminase binds and stimulates plasminogen activation on 1-LN human prostate cancer cells. Gonzalez-Gronow, M., Hershfield, M.S., Arredondo-Vega, F.X., Pizzo, S.V. J. Biol. Chem. (2004) [Pubmed]
  26. Connecting p63 to cellular proliferation: the example of the adenosine deaminase target gene. Sbisà, E., Mastropasqua, G., Lefkimmiatis, K., Caratozzolo, M.F., D'Erchia, A.M., Tullo, A. Cell Cycle (2006) [Pubmed]
  27. Mechanism of interferon action: functionally distinct RNA-binding and catalytic domains in the interferon-inducible, double-stranded RNA-specific adenosine deaminase. Liu, Y., Samuel, C.E. J. Virol. (1996) [Pubmed]
  28. Enhancement of methotrexate nephrotoxicity after cisplatin therapy. Goren, M.P., Wright, R.K., Horowitz, M.E., Meyer, W.H. Cancer (1986) [Pubmed]
  29. An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover. Hirschhorn, R., Yang, D.R., Israni, A. Ann. Hum. Genet. (1994) [Pubmed]
  30. Comodulation of CXCR4 and CD26 in human lymphocytes. Herrera, C., Morimoto, C., Blanco, J., Mallol, J., Arenzana, F., Lluis, C., Franco, R. J. Biol. Chem. (2001) [Pubmed]
  31. Resistance of an adenosine kinase-deficient human lymphoblastoid cell line to effects of deoxyadenosine on growth, S-adenosylhomocysteine hydrolase inactivation, and dATP accumulation. Hershfield, M.S., Kredich, N.M. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  32. Modulating effect of adenosine deaminase on function of adenosine A1 receptors. Sun, W.C., Cao, Y., Jin, L., Wang, L.Z., Meng, F., Zhu, X.Z. Acta Pharmacol. Sin. (2005) [Pubmed]
  33. Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response. Dong, R.P., Kameoka, J., Hegen, M., Tanaka, T., Xu, Y., Schlossman, S.F., Morimoto, C. J. Immunol. (1996) [Pubmed]
  34. Effects of adenosine analogues on ATP concentrations in human erythrocytes. Further evidence for a route independent of adenosine kinase. Smolenski, R.T., Montero, C., Duley, J.A., Simmonds, H.A. Biochem. Pharmacol. (1991) [Pubmed]
  35. Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts. Nakamachi, Y., Koshiba, M., Nakazawa, T., Hatachi, S., Saura, R., Kurosaka, M., Kusaka, H., Kumagai, S. Arthritis Rheum. (2003) [Pubmed]
  36. Adenosine deaminase, 5'nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human bladder tissues. Durak, I., Perk, H., Kavutçu, M., Canbolat, O., Akyol, O., Bedük, Y. Free Radic. Biol. Med. (1994) [Pubmed]
  37. Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients. Markert, M.L., Hershfield, M.S., Schiff, R.I., Buckley, R.H. J. Clin. Immunol. (1987) [Pubmed]
  38. Cloning of human adenosine deaminase cDNA and expression in mouse cells. Valerio, D., McIvor, R.S., Williams, S.R., Duyvesteyn, M.G., van Ormondt, H., van der Eb, A.J., Martin, D.W. Gene (1984) [Pubmed]
  39. Characterisation of human dipeptidyl peptidase IV expressed in Pichia pastoris. A structural and mechanistic comparison between the recombinant human and the purified porcine enzyme. Bär, J., Weber, A., Hoffmann, T., Stork, J., Wermann, M., Wagner, L., Aust, S., Gerhartz, B., Demuth, H.U. Biol. Chem. (2003) [Pubmed]
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