Adenosine deaminase

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. 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. Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change. Stimulates plasminogen activation. Plays a role in male fertility. Plays a protective role in early postimplantation embryonic development (By similarity). Also responsible for the deamination of cordycepin (3'-deoxyadenosine), a fungal natural product that shows antitumor, antibacterial, antifungal, antivirus, and immune regulation properties.

Classification

Family (Pfam)

PF00962 A_deaminase

InterPro

A/AMP_deam_AS, A_deaminase, A_deaminase_dom, Ado/ade_deaminase, Metal_Hydrolase

Functional cluster

Oxidoreductases, Catalases & Peroxidases

Experimental structures · PDB · 2

• 3IAR X-ray 1.52A
• 7RTG X-ray 2.59A

A predicted model is available from AlphaFold.

Gene Ontology · 29

• GO:0070161 anchoring junction
• GO:0009986 cell surface
• GO:0060205 cytoplasmic vesicle lumen
• GO:0005829 cytosol
• GO:0009897 external side of plasma membrane
• GO:0005764 lysosome
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0046936 2'-deoxyadenosine deaminase activity
• GO:0004000 adenosine deaminase activity
• GO:0019239 deaminase activity
• GO:0008270 zinc ion binding
• GO:0006154 adenosine catabolic process
• GO:0046085 adenosine metabolic process
• GO:0006196 AMP catabolic process
• GO:0007155 cell adhesion
• GO:0046059 dAMP catabolic process
• GO:0043103 hypoxanthine salvage
• GO:0046103 inosine biosynthetic process
• GO:0060169 negative regulation of adenosine receptor signaling pathway
• GO:0032261 purine nucleotide salvage
• GO:0009168 purine ribonucleoside monophosphate biosynthetic process
• GO:0043101 purine-containing compound salvage
• GO:0033632 regulation of cell-cell adhesion mediated by integrin
• GO:0045187 regulation of circadian sleep/wake cycle, sleep
• GO:0001666 response to hypoxia
• GO:0014074 response to purine-containing compound
• GO:0042110 T cell activation
• GO:0006805 xenobiotic metabolic process

Disease associations

• severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency MONDO:0007064

Drugs targeting this protein · 2

• PENTOSTATIN inhibitor
• COFORMYCIN inhibitor

Related proteins · sequence + function similarity

• Adenosine deaminase 0.96
• Adenosine deaminase 0.95
• Adenosine deaminase 0.95
• Adenosine deaminase 0.89
• Adenosine deaminase 0.89
• Adenosine deaminase 0.89
• Adenosine deaminase 0.86
• Adenine deaminase 0.63
• N6-Methyl-AMP deaminase 0.63
• Adenine deaminase 0.62
• Adenine deaminase 0.62
• Adenine deaminase 0.61

Co-cited proteins · studied together in the literature

• Dipeptidyl peptidase 4 7 shared papers
• Adenosine deaminase 1 shared papers
• Acyl-coenzyme A thioesterase 9, mitochondrial 1 shared papers
• Plasminogen 1 shared papers
• ATP-binding cassette sub-family B member 5 1 shared papers
• Actin-binding LIM protein 2 1 shared papers
• Disintegrin and metalloproteinase domain-containing protein 11 1 shared papers
• Rho GTPase-activating protein SYDE1 1 shared papers
• Glucosylceramide transporter ABCA12 1 shared papers
• Disintegrin and metalloproteinase domain-containing protein 19 1 shared papers
• Acetyl-CoA carboxylase 2 1 shared papers
• ATP-binding cassette sub-family D member 2 1 shared papers

Literature · 41 cited papers

• The Role of G22 A Adenosine Deaminase 1 Gene Polymorphism and the Activities of ADA Isoenzymes in Fertile and Infertile Men. Urology · 2015
• Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances. Pharmacol. Res. Perspect. · 2015
• The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors. FASEB J. · 2013
• Adenosine deaminase activity in fertile and infertile men. Andrologia · 2012
• Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans. Cereb. Cortex · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells. J. Leukoc. Biol. · 2011
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science · 2008
• Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26. Blood · 2006
• 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
• … and 29 more in the literature graph