General Information of MET (ID: META00442)
Name dATP
Synonyms   Click to Show/Hide Synonyms of This Metabolite
2'-Deoxyadenosine 5'-triphosphate, Deoxyadenosine 5'-triphosphate, 2'-Deoxyadenosine 5'-triphosphoric acid, Deoxyadenosine 5'-triphosphoric acid, 'Deoxyadenosine triphosphoric acid', 2'-Deoxy-5'-ATP, 2'-Deoxy-ATP, 2'-Deoxyadenosine triphosphate, 'dATP; Deoxy-ATP; Deoxyadenosine-triphosphate', 2'-Deoxyadenosine triphosphate, 14C-labeled, 2'-Deoxyadenosine triphosphate, monomagnesium salt, 2'-Deoxyadenosine triphosphate, trisodium salt, 2'-Deoxyadenosine triphosphate, p'-(32)p-labeled, 'dATP CPD
Source Endogenous;Escherichia Coli Metabolite;Yeast Metabolite;Food;Toxins/Pollutant;Microbial
Structure Type   Purine deoxyribonucleotides  (Click to Show/Hide the Complete Structure Type Hierarchy)
Nucleosides, nucleotides, and analogues
Purine nucleotides
Purine deoxyribonucleotides
PubChem CID
15993
HMDB ID
HMDB0001532
Formula
C10H16N5O12P3
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00131
DrugBank ID
DB03222
ChEBI ID
16284
FooDB ID
FDB022674
ChemSpider ID
15194
METLIN ID
6303
Physicochemical Properties Molecular Weight 491.18 Topological Polar Surface Area 259
XlogP -4.4 Complexity 769
Heavy Atom Count 30 Rotatable Bond Count 8
Hydrogen Bond Donor Count 6 Hydrogen Bond Acceptor Count 16
Function
Deoxyadenosine triphosphate (dATP) is a purine nucleoside triphosphate used in cells for DNA synthesis. A nucleoside triphosphate is a molecule type that contains a nucleoside with three phosphates bound to it. dATP contains the sugar deoxyribose, a precursor to DNA synthesis whereby the two existing phosphate groups are cleaved with the remaining deoxyadenosine monophosphate being incorporated into DNA during replication. Due to its enzymatic incorporation into DNA, photoreactive dATP analogs such as N6-[4-azidobenzoyl(2-aminoethyl)]-2-deoxyadenosine-5-triphosphate (AB-dATP) and N6-[4-[3-(trifluoromethyl)-diazirin-3-yl]benzoyl-(2-aminoethyl)]-2-deoxyadenosine-5-triphosphate (DB-dATP) have been used for DNA photoaffinity labeling. When present in sufficiently high levels, dATP can act as an immunotoxin and a metabotoxin. An immunotoxin disrupts, limits the function, or destroys immune cells. A metabotoxin is an endogenous metabolite that causes adverse health effects at chronically high levels. Chronically high levels of deoxyadenosine triphosphate are associated with adenosine deaminase (ADA) deficiency, an inborn error of metabolism. ADA deficiency damages the immune system and causes severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread skin rashes. The mechanism by which dATP functions as an immunotoxin is as follows: a buildup of dATP in cells inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are unable to divide and propagate to respond to immune challenges.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Hydrolases (EC 3)
            Leukotriene-C4 hydrolase (GGT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change dATP concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Renal cell carcinoma [ICD-11: 2C90]
                      Details It is reported that knockdown of GGT1 leads to the increase of dATP levels compared with control group.
      Sugar transporter (ST)
            Facilitated glucose transporter 1 (SLC2A1A) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Downregulation of slc2a1a caused by Yap loss-of-function mutation
                      Induced Change dATP concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that downregulation of slc2a1a caused by Yap loss-of-function mutation leads to the decrease of dATP levels compared with control group.
      Transcriptional coactivator (TC)
            Transcriptional coactivator YAP1 (yap1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Decrease of Yap mRNA caused by Yap loss-of-function mutation
                      Induced Change dATP concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that decrease of Yap mRNA caused by Yap loss-of-function mutation leads to the decrease of dATP levels compared with control group.
References
1 Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6274-E6282.
2 Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. EMBO J. 2018 Nov 15;37(22):e100294.

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