BRENDA - Enzyme Database show
show all sequences of 1.1.1.270

Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action

Steckelbroeck, S.; Jin, Y.; Gopishetty, S.; Oyesanmi, B.; Penning, T.M.; J. Biol. Chem. 279, 10784-10795 (2004)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
overexpression in Escherichia coli
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
Flufenamic acid
inhibits 3alpha-diol versus 3beta-diol formation
Homo sapiens
additional information
NADPH-dependent 3-ketosteroid reductase activity is not inhibited by NAD+
Homo sapiens
NADPH
potent inhibition of hydroxysteroid oxidase activity by low micromolar concentrations
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0043
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
Homo sapiens
AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q04828
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
Hep-G2 cell
HepG2 cells which lack 3-ketohydroxysteroid reductase/DELTA5-4ketosteroid isomerase mRNA expression, but express AKR1C1-AKR1C3 are able to convert 17beta-hydroxy-5alpha-androstan-3-one to 3beta-androstanediol and 3alpha-androstanediol
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
-
656200
Homo sapiens
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
the rates of 3alpha-diol versus 3beta-diol formation varies significantly among the isoforms. AKR1C1 predominantly catalyzes the formation of 3beta-diol, whereas AKR1C2 and AKR1C4 predominantly catalyze the formation of 3alpha-diol. AKR1C3 shows relatively low reductive activity towards 17beta-hydroxy-5alpha-androstan-3-one, in which 3alpha-diol and 3beta-diol is formed in almost equal amounts
-
-
?
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists
656200
Homo sapiens
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
-
-
-
?
3alpha-androstanediol + NAD+
AKR1C2 and AKR1C4 act as 3alpha-hydroxysteroid oxidase, AKR1C3 predominantly acts as 17beta-hydroxysteroid oxidase catalyzing the conversion of 3alpha-diol to androsterone, negligible activity with the 3beta-androstanediol
656200
Homo sapiens
? + NADH
-
-
-
?
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.003
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, radiometric analysis, formation of 3beta-androstanediol
Homo sapiens
0.0493
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, radiometric analysis, formation of 3alpha-androstanediol
Homo sapiens
0.052
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol
Homo sapiens
Cofactor
Cofactor
Commentary
Organism
Structure
NADP+
-
Homo sapiens
NADPH
-
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
overexpression in Escherichia coli
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
NADP+
-
Homo sapiens
NADPH
-
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
Flufenamic acid
inhibits 3alpha-diol versus 3beta-diol formation
Homo sapiens
additional information
NADPH-dependent 3-ketosteroid reductase activity is not inhibited by NAD+
Homo sapiens
NADPH
potent inhibition of hydroxysteroid oxidase activity by low micromolar concentrations
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0043
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
Homo sapiens
AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
-
-
?
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
Hep-G2 cell
HepG2 cells which lack 3-ketohydroxysteroid reductase/DELTA5-4ketosteroid isomerase mRNA expression, but express AKR1C1-AKR1C3 are able to convert 17beta-hydroxy-5alpha-androstan-3-one to 3beta-androstanediol and 3alpha-androstanediol
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
-
656200
Homo sapiens
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
the rates of 3alpha-diol versus 3beta-diol formation varies significantly among the isoforms. AKR1C1 predominantly catalyzes the formation of 3beta-diol, whereas AKR1C2 and AKR1C4 predominantly catalyze the formation of 3alpha-diol. AKR1C3 shows relatively low reductive activity towards 17beta-hydroxy-5alpha-androstan-3-one, in which 3alpha-diol and 3beta-diol is formed in almost equal amounts
-
-
?
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists
656200
Homo sapiens
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
-
-
-
?
3alpha-androstanediol + NAD+
AKR1C2 and AKR1C4 act as 3alpha-hydroxysteroid oxidase, AKR1C3 predominantly acts as 17beta-hydroxysteroid oxidase catalyzing the conversion of 3alpha-diol to androsterone, negligible activity with the 3beta-androstanediol
656200
Homo sapiens
? + NADH
-
-
-
?
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.003
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, radiometric analysis, formation of 3beta-androstanediol
Homo sapiens
0.0493
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, radiometric analysis, formation of 3alpha-androstanediol
Homo sapiens
0.052
-
17beta-hydroxy-5alpha-androstan-3-one
pH 7.0, 37C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol
Homo sapiens
Other publictions for EC 1.1.1.270
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [C]
Temperature Range [C]
Temperature Stability [C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [C] (protein specific)
Temperature Range [C] (protein specific)
Temperature Stability [C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
740936
Ferrante
4-Methylzymosterone and other ...
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51
1103-1113
2016
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1
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741250
Chen
Metabolism of androstenone, 17 ...
Sus scrofa
PLoS ONE
10
e113194
2015
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1
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1
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1
1
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726098
Debieu
Role of sterol 3-ketoreductase ...
Botrytis cinerea
Pest Manag. Sci.
69
642-651
2013
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1
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2
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740097
Layer
Characterization of a mutation ...
Mus musculus
Biochim. Biophys. Acta
1831
361-369
2013
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1
1
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724124
Endo
Characterization of rabbit ald ...
Oryctolagus cuniculus
Arch. Biochem. Biophys.
527
23-30
2012
-
-
1
-
4
-
14
20
1
-
1
1
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3
-
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1
-
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6
-
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27
-
1
-
-
21
1
-
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2
-
-
14
-
-
1
2
-
4
-
14
14
-
20
1
-
1
1
-
-
-
1
-
6
-
-
27
-
1
-
-
21
1
-
-
-
-
3
3
-
-
-
702462
Taramino
Interactions of oxidosqualene ...
Saccharomyces cerevisiae
Biochim. Biophys. Acta
1801
156-162
2010
-
-
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3
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-
-
-
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1
1
-
-
-
711300
Taramino
Divergent interactions involvi ...
Homo sapiens, Mus musculus
Biochim. Biophys. Acta
1801
1232-1237
2010
-
-
-
-
2
-
-
-
-
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7
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1
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1
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1
1
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725813
Thomas
The functions of key residues ...
Homo sapiens
J. Steroid Biochem. Mol. Biol.
120
192-199
2010
-
1
1
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6
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1
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2
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1
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6
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7
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1
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4
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1
1
2
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6
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1
4
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1
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6
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7
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1
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1
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3
3
-
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673822
Tam
Activities of 3beta-HSD and ar ...
Taeniopygia guttata
Gen. Comp. Endocrinol.
150
26-33
2006
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3
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1
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675595
Steckelbroeck
Tibolone metabolism in human l ...
Homo sapiens
J. Pharmacol. Exp. Ther.
316
1300-1309
2006
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1
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3
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3
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1
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1
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677144
Jin
Molecular docking simulations ...
Homo sapiens
Steroids
71
380-391
2006
-
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2
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2
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5
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656200
Steckelbroeck
Human cytosolic 3alpha-hydroxy ...
Homo sapiens
J. Biol. Chem.
279
10784-10795
2004
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1
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3
1
2
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655348
Rizner
Human type 3 3alpha-hydroxyste ...
Homo sapiens
Endocrinology
144
2922-2932
2003
-
-
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1
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1
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656795
Marijanovic
Closing the gap: Identificatio ...
Homo sapiens, Mus musculus
Mol. Endocrinol.
17
1715-1725
2003
-
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2
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1
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2
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2
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5
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5
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5
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4
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723672
Mo
Protein-protein interactions a ...
Saccharomyces cerevisiae
Proc. Natl. Acad. Sci. USA
99
39-44
2002
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1
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5
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286477
Huang
Gene structure, chromosomal lo ...
Homo sapiens
Biochim. Biophys. Acta
1520
124-130
2001
-
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1
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3
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3
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1
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286474
Pascal
Plant sterol biosynthesis: ide ...
Zea mays
Arch. Biochem. Biophys.
312
260-271
1994
1
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2
11
2
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2
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3
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1
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2
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27
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3
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1
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3
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2
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11
2
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2
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2
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27
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3
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1
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1
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1
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1
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3
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1
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11
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1
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1
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1
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1
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1
1
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1
1
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1
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2
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1
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11
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1
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1
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1
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3
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1
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1
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1
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1
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4
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2
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1
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3
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1
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1
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1
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1
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7
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1
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1
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2
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2
1
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2
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4
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2
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2
2
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1
3
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1
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1
1
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7
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1
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1
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2
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2
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4
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7
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1
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2
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1
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1
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2
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1
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4
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7
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1
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2
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