Adenosine deaminase

Details

Name
Adenosine deaminase
Synonyms
  • 3.5.4.4
  • ADA1
  • Adenosine aminohydrolase
Gene Name
ADA
UniProtKB Entry
P00813Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
2'-deoxyadenosine deaminase activity / deaminase activity
Processes
adenosine metabolic process / allantoin metabolic process / alpha-beta T cell differentiation / amide catabolic process / AMP catabolic process / AMP salvage / B cell proliferation / calcium-mediated signaling / cell adhesion / dAMP catabolic process / germinal center formation / GMP salvage / leukocyte migration / mature B cell apoptotic process / mucus secretion / penile erection / response to inorganic substance / response to purine-containing compound / smooth muscle contraction / T cell differentiation in thymus / T cell receptor signaling pathway / thymocyte apoptotic process / xenobiotic metabolic process
Components
anchoring junction / cytoplasmic vesicle lumen
General Function
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:16670267, PubMed:23193172, PubMed:26166670, PubMed:8452534, PubMed:9361033). 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)
Specific Function
2'-deoxyadenosine deaminase activity
Pfam Domain Function
Signal Regions
Not Available
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
20q13.12
External Identifiers
ResourceLink
UniProtKB IDP00813
UniProtKB Entry NameADA_HUMAN
GenBank Protein ID28380
GenBank Gene IDX02994
GeneCard IDADA
GenAtlas IDADA
HGNC IDHGNC:186
PDB ID(s)3IAR, 7RTG
KEGG IDhsa:100
IUPHAR/Guide To Pharmacology ID1230
NCBI Gene ID100
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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Associated Data

Bio-Entities
Bio-EntityType
Adenosine deaminase (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
7,8-dihydroinosineexperimentalunknowntargetDetails
6-hydroxy-1,6-dihydro purine nucleosideexperimentalyestargetinhibitorDetails
1-Deaza-AdenosineexperimentalyestargetinhibitorDetails
NebularineexperimentalyestargetinhibitorDetails
DipyridamoleapprovedyestargetinhibitorDetails
Pentostatinapproved, investigationalyestargetinhibitorDetails
Adenosineapproved, investigationalunknownenzymesubstrateDetails
Vidarabineapproved, investigationalunknownenzymesubstrateDetails
TheophyllineapprovedunknownenzymeinhibitorinducerDetails
Nelarabineapproved, investigationalnoenzymesubstrateDetails
(2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-olexperimentalyestargetinhibitorDetails
FR117016experimentalyestargetinhibitorDetails
FR221647experimentalyestargetinhibitorDetails
FR230513experimentalyestargetinhibitorDetails
1-((1R)-1-(HYDROXYMETHYL)-3-{6-[(3-PHENYLPROPANOYL)AMINO]-1H-INDOL-1-YL}PROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDEexperimentalunknowntargetDetails
FR-234938experimentalyestargetinhibitorDetails
FR239087experimentalyestargetinhibitorDetails
FR236913experimentalyestargetinhibitorDetails
1-{(1R,2S)-2-HYDROXY-1-[2-(2-NAPHTHYLOXY)ETHYL]PROPYL}-1H-IMIDAZONE-4-CARBOXAMIDEexperimentalunknowntargetDetails
1-((1R,2S)-1-{2-[2-(4-CHLOROPHENYL)-1,3-BENZOXAZOL-7-YL]ETHYL}-2-HYDROXYPROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDEexperimentalunknowntargetDetails
Edetic acidapproved, vet_approvedunknownenzymeinhibitorDetails
Erdosteineapproved, investigationalunknownenzymeinhibitorDetails
Edetate disodium anhydrousapproved, vet_approvedunknownenzymeinhibitorDetails
Edetate calcium disodium anhydrousapprovedunknownenzymeinhibitorDetails
S-9-(2-hydroxypropyl)adenineexperimentalunknowntargetinhibitorDetails
Cladribineapproved, investigationalyestargetinhibitorDetails
FludarabineapprovedyestargetinhibitorDetails