Adenosine deaminase

NameAdenosine deaminase
Synonyms
  • 3.5.4.4
  • ADA1
  • Adenosine aminohydrolase
Gene NameADA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0020603|Adenosine deaminase
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
QNL
Number of residues363
Molecular Weight40764.13
Theoretical pI5.8
GO Classification
Functions
  • zinc ion binding
  • purine nucleoside binding
  • adenosine deaminase activity
Processes
  • liver development
  • small molecule metabolic process
  • Peyer's patch development
  • positive regulation of alpha-beta T cell differentiation
  • placenta development
  • negative regulation of mature B cell apoptotic process
  • T cell activation
  • positive regulation of T cell receptor signaling pathway
  • aging
  • negative regulation of thymocyte apoptotic process
  • positive regulation of T cell differentiation in thymus
  • response to vitamin E
  • positive regulation of calcium-mediated signaling
  • purine ribonucleoside monophosphate biosynthetic process
  • response to hydrogen peroxide
  • adenosine catabolic process
  • response to hypoxia
  • inosine biosynthetic process
  • negative regulation of circadian sleep/wake cycle, non-REM sleep
  • positive regulation of smooth muscle contraction
  • hypoxanthine salvage
  • dATP catabolic process
  • negative regulation of leukocyte migration
  • nucleobase-containing small molecule metabolic process
  • deoxyadenosine catabolic process
  • negative regulation of penile erection
  • response to drug
  • negative regulation of mucus secretion
  • purine nucleobase metabolic process
  • germinal center B cell differentiation
  • purine nucleotide salvage
  • response to morphine
  • purine-containing compound salvage
  • histamine secretion
  • trophectodermal cell differentiation
  • lung alveolus development
  • negative regulation of inflammatory response
  • negative regulation of adenosine receptor signaling pathway
  • xanthine biosynthetic process
  • positive regulation of heart rate
  • positive regulation of B cell proliferation
  • embryonic digestive tract development
  • regulation of cell-cell adhesion mediated by integrin
  • positive regulation of germinal center formation
Components
  • cytosol
  • external side of plasma membrane
  • cytoplasmic membrane-bounded vesicle lumen
  • cytoplasm
  • membrane
  • plasma membrane
  • extracellular space
  • lysosome
  • dendrite cytoplasm
  • cell surface
  • neuronal cell body
  • cell junction
General FunctionZinc ion binding
Specific FunctionCatalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. 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. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID28380
UniProtKB IDP00813
UniProtKB Entry NameADA_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0020604|Adenosine deaminase (ADA)
ATGGCCCAGACGCCCGCCTTCGACAAGCCCAAAGTAGAACTGCATGTCCACCTAGACGGA
TCCATCAAGCCTGAAACCATCTTATACTATGGCAGGAGGAGAGGGATCGCCCTCCCAGCT
AACACAGCAGAGGGGCTGCTGAACGTCATTGGCATGGACAAGCCGCTCACCCTTCCAGAC
TTCCTGGCCAAGTTTGACTACTACATGCCTGCTATCGCGGGCTGCCGGGAGGCTATCAAA
AGGATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCGTGGTGTATGTGGAGGTG
CGGTACAGTCCGCACCTGCTGGCCAACTCCAAAGTGGAGCCAATCCCCTGGAACCAGGCT
GAAGGGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTGGGCCAGGGCCTGCAGGAGGGG
GAGCGAGACTTCGGGGTCAAGGCCCGGTCCATCCTGTGCTGCATGCGCCACCAGCCCAAC
TGGTCCCCCAAGGTGGTGGAGCTGTGTAAGAAGTACCAGCAGCAGACCGTGGTAGCCATT
GACCTGGCTGGAGATGAGACCATCCCAGGAAGCAGCCTCTTGCCTGGACATGTCCAGGCC
TACCAGGAGGCTGTGAAGAGCGGCATTCACCGTACTGTCCACGCCGGGGAGGTGGGCTCG
GCCGAAGTAGTAAAAGAGGCTGTGGACATACTCAAGACAGAGCGGCTGGGACACGGCTAC
CACACCCTGGAAGACCAGGCCCTTTATAACAGGCTGCGGCAGGAAAACATGCACTTCGAG
ATCTGCCCCTGGTCCAGCTACCTCACTGGTGCCTGGAAGCCGGACACGGAGCATGCAGTC
ATTCGGCTCAAAAATGACCAGGCTAACTACTCGCTCAACACAGATGACCCGCTCATCTTC
AAGTCCACCCTGGACACTGATTACCAGATGACCAAACGGGACATGGGCTTTACTGAAGAG
GAGTTTAAAAGGCTGAACATCAATGCGGCCAAATCTAGTTTCCTCCCAGAAGATGAAAAG
AGGGAGCTTCTCGACCTGCTCTATAAAGCCTATGGGATGCCACCTTCAGCCTCTGCAGGG
CAGAACCTCTGA
GenBank Gene IDX02994
GeneCard IDNot Available
GenAtlas IDADA
HGNC IDHGNC:186
Chromosome Location20
Locus20q12-q13.11
References
  1. Daddona PE, Shewach DS, Kelley WN, Argos P, Markham AF, Orkin SH: Human adenosine deaminase. cDNA and complete primary amino acid sequence. J Biol Chem. 1984 Oct 10;259(19):12101-6. 6090454
  2. Wiginton DA, Adrian GS, Hutton JJ: Sequence of human adenosine deaminase cDNA including the coding region and a small intron. Nucleic Acids Res. 1984 Mar 12;12(5):2439-46. 6546794
  3. Valerio D, Duyvesteyn MG, Dekker BM, Weeda G, Berkvens TM, van der Voorn L, van Ormondt H, van der Eb AJ: Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985 Feb;4(2):437-43. 3839456
  4. Wiginton DA, Kaplan DJ, States JC, Akeson AL, Perme CM, Bilyk IJ, Vaughn AJ, Lattier DL, Hutton JJ: Complete sequence and structure of the gene for human adenosine deaminase. Biochemistry. 1986 Dec 16;25(25):8234-44. 3028473
  5. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Orkin SH, Daddona PE, Shewach DS, Markham AF, Bruns GA, Goff SC, Kelley WN: Molecular cloning of human adenosine deaminase gene sequences. J Biol Chem. 1983 Nov 10;258(21):12753-6. 6688808
  8. Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C: Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993 Jul 23;261(5120):466-9. 8101391
  9. De Meester I, Vanham G, Kestens L, Vanhoof G, Bosmans E, Gigase P, Scharpe S: Binding of adenosine deaminase to the lymphocyte surface via CD26. Eur J Immunol. 1994 Mar;24(3):566-70. 7907293
  10. Durinx C, Lambeir AM, Bosmans E, Falmagne JB, Berghmans R, Haemers A, Scharpe S, De Meester I: Molecular characterization of dipeptidyl peptidase activity in serum: soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides. Eur J Biochem. 2000 Sep;267(17):5608-13. 10951221
  11. Gines S, Marino M, Mallol J, Canela EI, Morimoto C, Callebaut C, Hovanessian A, Casado V, Lluis C, Franco R: Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. Biochem J. 2002 Jan 15;361(Pt 2):203-9. 11772392
  12. Aertgeerts K, Ye S, Shi L, Prasad SG, Witmer D, Chi E, Sang BC, Wijnands RA, Webb DR, Swanson RV: N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding. Protein Sci. 2004 Jan;13(1):145-54. 14691230
  13. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  14. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  15. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  16. Hirschhorn R, Tzall S, Ellenbogen A: Hot spot mutations in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6171-5. 2166947
  17. Hirschhorn R, Yang DR, Israni A: An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover. Ann Hum Genet. 1994 Jan;58(Pt 1):1-9. 8031011
  18. Adrian GS, Wiginton DA, Hutton JJ: Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. Mol Cell Biol. 1984 Sep;4(9):1712-7. 6208479
  19. Bonthron DT, Markham AF, Ginsburg D, Orkin SH: Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency. J Clin Invest. 1985 Aug;76(2):894-7. 3839802
  20. Akeson AL, Wiginton DA, Dusing MR, States JC, Hutton JJ: Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts. J Biol Chem. 1988 Nov 5;263(31):16291-6. 3182793
  21. Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH: Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency. J Clin Invest. 1989 Feb;83(2):497-501. 2783588
  22. Hirschhorn R: Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for response to therapy with partial exchange transfusions. Hum Mutat. 1992;1(2):166-8. 1284479
  23. Santisteban I, Arredondo-Vega FX, Kelly S, Mary A, Fischer A, Hummell DS, Lawton A, Sorensen RU, Stiehm ER, Uribe L, et al.: Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype. J Clin Invest. 1993 Nov;92(5):2291-302. 8227344
  24. Yang DR, Huie ML, Hirschhorn R: Homozygosity for a missense mutation (G20R) associated with neonatal onset adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID). Clin Immunol Immunopathol. 1994 Feb;70(2):171-5. 8299233
  25. Santisteban I, Arredondo-Vega FX, Kelly S, Loubser M, Meydan N, Roifman C, Howell PL, Bowen T, Weinberg KI, Schroeder ML, et al.: Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA. Hum Mol Genet. 1995 Nov;4(11):2081-7. 8589684
  26. Santisteban I, Arredondo-Vega FX, Kelly S, Debre M, Fischer A, Perignon JL, Hilman B, elDahr J, Dreyfus DH, Gelfand EW, et al.: Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site. Hum Mutat. 1995;5(3):243-50. 7599635
  27. Hirschhorn R, Borkowsky W, Jiang CK, Yang DR, Jenkins T: Two newly identified mutations (Thr233Ile and Leu152Met) in partially adenosine deaminase-deficient (ADA-) individuals that result in differing biochemical and metabolic phenotypes. Hum Genet. 1997 Jul;100(1):22-9. 9225964
  28. Arrendondo-Vega FX, Santisteban I, Notarangelo LD, El Dahr J, Buckley R, Roifman C, Conley ME, Hershfield MS: Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del. Mutations in brief no. 142. Online. Hum Mutat. 1998;11(6):482. 10200056
  29. Retey JV, Adam M, Honegger E, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP: A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15676-81. Epub 2005 Oct 12. 16221767
  30. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801-6. doi: 10.1126/science.1164368. Epub 2008 Sep 4. 18772397