Information on EC 3.5.4.38 - single-stranded DNA cytosine deaminase

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The expected taxonomic range for this enzyme is: Tetrapoda

EC NUMBER
COMMENTARY hide
3.5.4.38
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RECOMMENDED NAME
GeneOntology No.
single-stranded DNA cytosine deaminase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
cytosine in single-stranded DNA + H2O = uracil in single-stranded DNA + NH3
show the reaction diagram
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SYSTEMATIC NAME
IUBMB Comments
single-stranded DNA cytosine aminohydrolase
The enzyme exclusively catalyses deamination of cytosine in single-stranded DNA. It preferentially deaminates five-nucleotide bubbles. The optimal target consists of a single-stranded NWRCN motif (W = A or T, R = A or G) [2]. The enzyme initiates antibody diversification processes by deaminating immunoglobulin sequences.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Holstein Friesian cross calf
SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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deficiency in activation-induced deaminase is responsible for a human immunodeficiency
metabolism
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activation-induced deaminase initiated double-strand breaks and mutations may predispose B cells to carcinogenesis
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
show the reaction diagram
additional information
?
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activation-induced cytidine deaminase is function in Pleurodeles waltl. The lack of class switch recombination activity in Pleurodeles waltl is therefore not due to a defect in expression or function of activation-induced cytidine deaminase
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cytosine in single-stranded DNA + H2O
uracil in single-stranded DNA + NH3
show the reaction diagram
additional information
?
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D5GRW1
activation-induced cytidine deaminase is function in Pleurodeles waltl. The lack of class switch recombination activity in Pleurodeles waltl is therefore not due to a defect in expression or function of activation-induced cytidine deaminase
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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the enzyme requires a tightly bound metal ion for its action
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
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Fe2+
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inhibits AID-mediated dC deamination in a dose-dependent fashion
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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Km of glutathione S-transferase-AID for the hot-spot transcription bubble substrate HS1bub7 is between 10 and 15 nM. It is not possible to estimate the Km for the cold-spot bubble (i.e., CS1bub7) since the substrate saturation kinetics is not observed. However, as the velocity continues to increase beyond the highest substrate concentration tested, the Km is likely to be severalfold higher for CS1bub7 than for HS1bub7
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
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assay at
8
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assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6 - 9
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wide range of pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22 - 37
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the enzyme works with varying efficiencies from room temperature to 37°C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24000
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x * 24000, calculation from sequence
24050
calculated from sequence
24052
x * 24052, calculated from sequence
additional information
activation-induced cytidine deaminase mRNA is not alternatively spliced in Pleurodeles waltl
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
tetramer
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
ubiquitination
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the enzyme is polyubiquitinated in the nucleus. Ubiquitin-mediated nuclear degradation of the enzyme is part of a multilayer control that contributes to the regulation of enzyme function during hypermutation and class switch recombination
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65
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30 min, protein is active
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme displays a different stability depending on the specific cell compartment in which it is located. In a Burkitt’s lymphoma cell line the half-life of activation-induced cytidine deaminase is markedly reduced in the nucleus. This destabilization is accompanied by a polyubiquitination that is revealed in the presence of proteasome inhibitors. The same compartment-specific degradation is observed in activated mouse B cells, and also in a non–B cell line
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
activation-induced deaminase(AID)/APOBEC3G hybrid proteins
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
construction of stable transformants (mouse hybridoma cells) expressing human activation-induced cytidine deaminase
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expressed in Escherichia coli
expression in Escherichia coli as a glutathione S-transferase fusion protein
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expression in Escherichia coli. Human activation-induced cytidine deaminase purified from Escherichia coli is active without prior treatment with a ribonuclease and deaminates cytosines in plasmid DNA in vitro
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expression of 3H9 VDJ knock-in alleles in genomic DNA of immature/T1, mature follicular B cells, and thymocytes from 3H9 and 3H9.Aicda-/- mice, quantitative expression analysis by PCR and immunofluorescence
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is increased by epidermal growth factor, tumor necrosis factor alpha, or sodium butyrate
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expression of activation-induced cytidine deaminase mRNA is induced in splenic B cells that are activated in vitro or by immunizations with sheep red blood cells. In situ hybridization of immunized spleen sections reveals the restricted expression of AID mRNA in developing germinal centers in which modulation of immunoglobulin gene information through somatic hypermutation and class switch recombination takes place
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the enzyme is expressed in response to antigen activation
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C90A
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catalytically inactive
E58Q/C87A/C90A
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the mutant enzyme does not bind to single-stranded DNA at all, though it retains some binding to RNA
S3A
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purified recombinant mutant enzyme S3A and wild-type have similar deamination activities on an ssDNA substrate in vitro. AID-/- B cells expressing AIDS3A show a consistently higher percentage of class-switched IgG1-expressing B cells than control enzyme. Mutating S3 to A does not alter catalysis but does result in increased AID activity in class switch recombination
S3D
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AID-/- B cells expressing AID-S3D show a consistently higher percentage of class-switched IgG1-expressing B cells than control enzyme. Mutating S3 to A does not alter catalysis but does result in increased AID activity in class switch recombination
T140A
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mutation does not impact catalytic activity, but interfers with class switching and somatic hypermutation in vivo
additional information