Adenosine deaminase

Details

Name
Adenosine deaminase
Synonyms
  • 3.5.4.4
  • ADA1
  • Adenosine aminohydrolase
Gene Name
ADA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020603|Adenosine deaminase
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
QNL
Number of residues
363
Molecular Weight
40764.13
Theoretical pI
5.8
GO Classification
Functions
adenosine deaminase activity / purine nucleoside binding / zinc ion binding
Processes
adenosine catabolic process / aging / 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 / nucleobase-containing small molecule metabolic 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 nucleobase metabolic process / 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 / small molecule metabolic process / T cell activation / trophectodermal cell differentiation / xanthine biosynthetic process
Components
cell junction / cell surface / cytoplasm / cytoplasmic membrane-bounded vesicle lumen / cytosol / dendrite cytoplasm / external side of plasma membrane / extracellular space / lysosome / membrane / neuronal cell body / plasma membrane
General Function
Zinc ion binding
Specific Function
Catalyzes 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 Regions
Not Available
Cellular Location
Cell 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
Chromosome Location
20
Locus
20q12-q13.11
External Identifiers
ResourceLink
UniProtKB IDP00813
UniProtKB Entry NameADA_HUMAN
GenBank Protein ID28380
GenBank Gene IDX02994
GenAtlas IDADA
HGNC IDHGNC:186
General 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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:3028473]
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  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10200056]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB024726-Hydroxy-7,8-Dihydro Purine NucleosideexperimentalunknownDetails
DB030156-Hydroxy-1,6-Dihydro Purine NucleosideexperimentalunknownDetails
DB042181-Deaza-AdenosineexperimentalunknownDetails
DB04440NebularineexperimentalunknownDetails
DB00975DipyridamoleapprovedyesinhibitorDetails
DB00552Pentostatinapproved, investigationalyesinhibitorDetails
DB00640Adenosineapproved, investigationalunknownsubstrateDetails
DB00194Vidarabineapproved, investigationalunknownsubstrateDetails
DB00277TheophyllineapprovedunknowninhibitorinducerDetails
DB01280Nelarabineapproved, investigationalunknownsubstrateDetails
DB07711(2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-olexperimentalunknownDetails
DB02616FR117016experimentalunknownDetails
DB02096FR221647experimentalunknownDetails
DB03572FR230513experimentalunknownDetails
DB077831-((1R)-1-(HYDROXYMETHYL)-3-{6-[(3-PHENYLPROPANOYL)AMINO]-1H-INDOL-1-YL}PROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDEexperimentalunknownDetails
DB03220FR233623experimentalunknownDetails
DB03370FR239087experimentalunknownDetails
DB02830FR236913experimentalunknownDetails
DB077851-{(1R,2S)-2-HYDROXY-1-[2-(2-NAPHTHYLOXY)ETHYL]PROPYL}-1H-IMIDAZONE-4-CARBOXAMIDEexperimentalunknownDetails
DB077861-((1R,2S)-1-{2-[2-(4-CHLOROPHENYL)-1,3-BENZOXAZOL-7-YL]ETHYL}-2-HYDROXYPROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDEexperimentalunknownDetails
DB00974Edetic Acidapproved, vet_approvedunknowninhibitorDetails
DB05057Erdosteineapproved, investigationalunknowninhibitorDetails
DB14600Edetate disodium anhydrousapproved, vet_approvedunknownDetails