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Information on EC 1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase and Organism(s) Homo sapiens and UniProt Accession P42330

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EC Tree
IUBMB Comments
The enzyme acts on multiple 3alpha-hydroxysteroids, such as androsterone and 5 alpha-dihydrotestosterone. The mammalian enzymes are involved in inactivation of steroid hormones, while the bacterial enzymes are involved in steroid degradation. This entry stands for enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known. [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) and EC 1.1.1.213, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)].
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This record set is specific for:
Homo sapiens
UNIPROT: P42330
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
bile acid binding protein, aldo-keto reductase family 1 member c3, akr1c33, 3alpha-hsd type iii, aldo-keto reductase family 1 member c2, type 1 3alpha-hsd, 3alpha-hydroxysteroid dehydrogenase type iii, hsd 28, dihydrodiol dehydrogenase 4, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
17beta-HSD5
-
3-alpha-HSD type 2
UniProt
3-alpha-hydroxysteroid dehydrogenase type 2
UniProt
3alpha-HSD
type II
3alpha-hydroxysteroid dehydrogenase
-
aldo-keto reductase family 1 member C3
UniProt
type 5 17beta-hydroxysteroid dehydrogenase
-
3-alpha hydroxysteroid dehydrogenase type 3
-
3-alpha-HSD1
UniProt
3-alpha-hydroxysteroid dehydrogenase type I
UniProt
3alpha-HSD
3alpha-HSD type III
-
3alpha-HSD3
3alpha-HSOR
-
3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase type 3
-
3alpha-hydroxysteroid dehydrogenase type III
-
3alpha-hydroxysteroid oxidoreductase
-
AKR1C2
AKR1C4
aldo-keto reductase family 1 member C1
UniProt
aldo-keto reductase family 1 member C2
UniProt
bile acid binding protein
-
-
chlordecone reductase
-
dihydrodiol dehydrogenase
-
-
dihydrodiol dehydrogenase 4
-
dihydrodiol/3alpha-hydroxysteroid dehydrogenase
-
-
type 1 3alpha-HSD
-
type 3 3alpha-hydroxysteroid dehydrogenase
type I 3alpha-HSD
-
-
type III 3-alpha-hydroxysteroid dehydrogenase
UniProt
additional information
cf. EC 1.1.1.239
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase
The enzyme acts on multiple 3alpha-hydroxysteroids, such as androsterone and 5 alpha-dihydrotestosterone. The mammalian enzymes are involved in inactivation of steroid hormones, while the bacterial enzymes are involved in steroid degradation. This entry stands for enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known. [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) and EC 1.1.1.213, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-acenaphthenol + NADP+
acenaphthylen-1(2H)-one + NADPH + H+
show the reaction diagram
-
-
-
?
4-androstenedione + NADPH
?
show the reaction diagram
the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
-
-
?
4-hydroxyandrostenedione + NADPH
?
show the reaction diagram
the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
-
-
?
4-hydroxyandrostenedione + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+
show the reaction diagram
-
-
-
?
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
r
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
-
-
-
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
?
chenodeoxycholic acid + NADP+
(5beta,7alpha,8xi)-7-hydroxy-3-oxocholan-24-oic acid + NADPH + H+
show the reaction diagram
-
-
-
?
dihydrotestosterone + NADPH
?
show the reaction diagram
the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
-
-
?
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
show the reaction diagram
low activity
-
-
?
(R)-tetralol + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-1,2,3,4-tetrahydronaphth-1-ol + NADP+
1,2,3,4-tetrahydronaphth-1-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-indan-1-ol + NADP+
indan-1-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
1-tetralone + NADPH + H+
show the reaction diagram
-
-
-
-
?
1-acenaphthenol + NADP+
acenaphthylen-1(2H)-one + NADPH + H+
show the reaction diagram
-
-
-
?
17beta-estradiol + NAD(P)H + H+
estrone + NAD(P)+
show the reaction diagram
-
-
-
?
20alpha-hydroxyprogesterone + NAD(P)H + H+
progesterone + NAD(P)+
show the reaction diagram
-
-
-
?
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
show the reaction diagram
-
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
-
-
-
?
4-hydroxyandrostenedione + NADPH
?
show the reaction diagram
4-hydroxyandrostenedione + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+
show the reaction diagram
-
-
-
?
4-hydroxytestosterone + NADPH
?
show the reaction diagram
4-hydroxytestosterone + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-ol + NADP+
show the reaction diagram
-
-
-
?
5alpha-androstan-3alpha-ol-17-one + NADP+
(5alpha)-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-androstane-3,17-dione + NAD(P)H + H+
androsterone + NAD(P)+
show the reaction diagram
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
reaction of EC 1.1.1.149
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-dihydroprogesterone + NADPH + H+
pregnanolone + NADP+
show the reaction diagram
-
-
-
r
5beta-pregnane-3alpha,20alpha-diol + NADP+
(5beta)-pregnan-20alpha-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
9alpha,11beta-prostaglandin F2 + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
a 3-alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
-
-
-
?
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
show the reaction diagram
-
-
-
r
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H + H+
show the reaction diagram
-
-
-
?
androsterone + NAD+
(5alpha)-androstane-3,17-dione + NADH + H+
show the reaction diagram
-
-
-
-
?
androsterone + NADP+
(5alpha)-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
?
chenodeoxycholic acid + NADP+
(5beta,7alpha,8xi)-7-hydroxy-3-oxocholan-24-oic acid + NADPH + H+
show the reaction diagram
-
-
-
?
chenodeoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
cholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
deoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
dihydrotestosterone + NAD(P)H + H+
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
?
dihydrotestosterone + NADPH
?
show the reaction diagram
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
show the reaction diagram
estrone + NAD(P)H + H+
17beta-estradiol + NAD(P)+
show the reaction diagram
-
-
-
?
lithocholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
show the reaction diagram
-
-
-
r
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
-
-
?
testosterone + NAD(P)H + H+
DELTA4-androstene-3,17-dione + NAD(P)+
show the reaction diagram
-
-
-
?
testosterone + NADPH + H+
?
show the reaction diagram
the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4-hydroxyandrostenedione + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+
show the reaction diagram
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
-
-
-
r
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
show the reaction diagram
low activity
-
-
?
(R)-tetralol + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-indan-1-ol + NADP+
indan-1-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
1-tetralone + NADPH + H+
show the reaction diagram
-
-
-
-
?
17beta-estradiol + NAD(P)H + H+
estrone + NAD(P)+
show the reaction diagram
-
-
-
?
20alpha-hydroxyprogesterone + NAD(P)H + H+
progesterone + NAD(P)+
show the reaction diagram
-
-
-
?
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
show the reaction diagram
-
-
-
r
4-hydroxyandrostenedione + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+
show the reaction diagram
-
-
-
?
5alpha-androstane-3,17-dione + NAD(P)H + H+
androsterone + NAD(P)+
show the reaction diagram
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
reaction of EC 1.1.1.149
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
physiological inactivation of the most potent androgen 5alpha dihydrotestosterone
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-dihydroprogesterone + NADPH + H+
pregnanolone + NADP+
show the reaction diagram
-
-
-
r
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
show the reaction diagram
-
-
-
r
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H + H+
show the reaction diagram
-
-
-
?
androsterone + NAD+
(5alpha)-androstane-3,17-dione + NADH + H+
show the reaction diagram
-
-
-
-
?
androsterone + NADP+
(5alpha)-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
chenodeoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
cholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
deoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
show the reaction diagram
estrone + NAD(P)H + H+
17beta-estradiol + NAD(P)+
show the reaction diagram
-
-
-
?
lithocholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
-
-
?
testosterone + NAD(P)H + H+
DELTA4-androstene-3,17-dione + NAD(P)+
show the reaction diagram
-
-
-
?
additional information
?
-
-
isoform AKR1C2 functions preferentially as a 3-ketosteroid reductase
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
NADP+
NADPH
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone
crystal structure analysis of enzyme-inhibitor complex
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
crystal structure analysis of enzyme-inhibitor complex
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one
crystal structure analysis of enzyme-inhibitor complex
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide
crystal structure analysis of enzyme-inhibitor complex
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol
crystal structure analysis of enzyme-inhibitor complex
5-(benzenesulfonyl)-2-nitrophenol
crystal structure analysis of enzyme-inhibitor complex
17beta-estradiol
-
competitive inhibitor
3,5,3',5'-tetraiodothyropropionic acid
-
competitive inhibitor
chenodeoxycholic acid
-
-
Flufenamic acid
Hexestrol
-
-
Ibuprofen
-
-
indomethacin
-
-
lithocholic acid
-
-
Medroxyprogesterone acetate
-
-
Phenolphthalein
ursodeoxycholate
micromolar inhibitor, competitive inhibitor versus 5alpha-dihydroprogesterone and uncompetitive inhibitor versus NADPH
Ursodeoxycholic acid
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-ibuprofen
-
167% activity at 1 mM
Clofibric acid
-
240% activity at 0.1 mM
D-thyroxine
-
260% activity at 1 mM
L-thyroxine
-
237% activity at 1 mM
Sulfobromophthalein
-
328% activity at 0.005 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00212
4-androstenedione
pH 7.4, 37°C
0.0023
4-hydroxyandrostenedione
pH 7.4, 37°C
-
0.0192
5alpha-dihydrotestosterone
apparent Km-value, pH 7.4, 37°C
0.0117
dihydrotestosterone
pH 7.4, 37°C
0.16 - 0.68
(R)-tetralol
0.14 - 0.26
(S)-1,2,3,4-tetrahydronaphth-1-ol
0.146 - 0.52
(S)-indan-1-ol
0.11 - 0.29
(S)-tetralol
0.0105
3alpha-androstanediol
isoform AKR1C4, at pH 7.4 and 25°C
0.00843 - 0.03362
4-hydroxyandrostenedione
-
0.00603 - 0.02687
4-hydroxytestosterone
-
0.002 - 0.0022
5alpha-Androstan-3alpha-ol-17-one
0.00144
5alpha-androstane-3,17-dione
isoform AKR1C4, at pH 7.4 and 25°C
0.0008 - 0.0031
5alpha-androstane-3alpha,17beta-diol
0.0018
5alpha-dihydroprogesterone
in 100 mM potassium phosphate, pH 7.0, at 25°C
0.0012 - 0.07103
5alpha-dihydrotestosterone
0.0009 - 0.0018
5beta-Androstan-3alpha-ol-17-one
0.0012 - 0.0022
5beta-androstane-3alpha,17beta-diol
0.001
5beta-pregnane-3alpha,20alpha-diol
0.208 - 0.22
9alpha,11beta-prostaglandin F2
0.0015
allopregnanolone
in 100 mM potassium phosphate, pH 7.0, at 25°C
0.0005 - 0.00504
androsterone
0.0011 - 0.0029
chenodeoxycholic acid
0.032 - 0.059
cholic acid
0.0013 - 0.0097
deoxycholic acid
0.0011 - 0.016
dihydrotestosterone
0.001 - 0.0019
lithocholic acid
1 - 1.2
NAD+
0.00023 - 0.0017
NADP+
0.00007
NADPH
in 100 mM potassium phosphate, pH 7.0, at 25°C
0.00084 - 0.00213
pregn-4-en-3,20-dione
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0038
4-androstenedione
pH 7.4, 37°C
0.0052
4-hydroxyandrostenedione
pH 7.4, 37°C
-
0.00075
dihydrotestosterone
pH 7.4, 37°C
0.18 - 0.77
(R)-tetralol
0.2 - 0.27
(S)-1,2,3,4-tetrahydronaphth-1-ol
0.1 - 0.4
(S)-indan-1-ol
0.2 - 0.43
(S)-tetralol
0.035
3alpha-androstanediol
isoform AKR1C4, at pH 7.4 and 25°C
0.017 - 0.032
4-hydroxyandrostenedione
-
0.0078 - 0.025
4-hydroxytestosterone
-
0.007
5alpha-Androstan-3alpha-ol-17-one
0.03
5alpha-androstane-3,17-dione
isoform AKR1C4, at pH 7.4 and 25°C
0.087 - 0.35
5alpha-androstane-3alpha,17beta-diol
0.003
5alpha-dihydroprogesterone
in 100 mM potassium phosphate, pH 7.0, at 25°C
0.033 - 0.1153
5alpha-dihydrotestosterone
0.048 - 0.18
5beta-Androstan-3alpha-ol-17-one
0.047 - 0.3
5beta-androstane-3alpha,17beta-diol
0.002 - 0.003
5beta-pregnane-3alpha,20alpha-diol
0.083 - 0.42
9alpha,11beta-prostaglandin F2
0.000017
allopregnanolone
in 100 mM potassium phosphate, pH 7.0, at 25°C
0.023 - 0.28
androsterone
0.032 - 0.13
chenodeoxycholic acid
0.03 - 0.2
cholic acid
0.012 - 0.085
deoxycholic acid
0.0175 - 0.026
dihydrotestosterone
0.032 - 0.043
lithocholic acid
0.2 - 0.58
NAD+
0.04 - 0.25
NADP+
0.0035 - 0.0392
pregn-4-en-3,20-dione
0.032
testosterone
pH 7.4, 37°C
additional information
additional information
Kcat-value for the 17beta-oxidation of testosterone is 0.000118 1/sec, and Kcat-value for the 17beta-reduction of androstenedione is 0.00112 1/sec
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.8
4-androstenedione
pH 7.4, 37°C
2.25
4-hydroxyandrostenedione
pH 7.4, 37°C
-
0.75
dihydrotestosterone
pH 7.4, 37°C
1 - 1.2
(R)-tetralol
0.68 - 1
(S)-indan-1-ol
1.2 - 1.83
(S)-tetralol
3.33
3alpha-androstanediol
isoform AKR1C4, at pH 7.4 and 25°C
0.959 - 2.9
4-hydroxyandrostenedione
-
0.943 - 1.63
4-hydroxytestosterone
-
20.72
5alpha-androstane-3,17-dione
isoform AKR1C4, at pH 7.4 and 25°C
10.3 - 135
5alpha-androstane-3alpha,17beta-diol
1.623 - 28.07
5alpha-dihydrotestosterone
53.3 - 101.7
5beta-Androstan-3alpha-ol-17-one
4.6 - 105
androsterone
28.3 - 46.7
chenodeoxycholic acid
1 - 3.3
cholic acid
8.8 - 14.2
deoxycholic acid
1.43 - 22.7
dihydrotestosterone
21.7 - 31.7
lithocholic acid
166.7 - 583.3
NAD+
23.3 - 500
NADP+
4.167 - 18.4
pregn-4-en-3,20-dione
0.96
testosterone
pH 7.4, 37°C
additional information
additional information
Kcat/Km-value for the 17beta-oxidation of testosterone is 0.183 1/sec*mM, and Kcat/Km-value for the 17beta-reduction of androstenedione is 0.817 1/sec*mM
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone
Homo sapiens
pH 6.0, 22°C
0.000037
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
Homo sapiens
pH 6.0, 22°C
0.0029
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one
Homo sapiens
pH 6.0, 22°C
0.0026
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide
Homo sapiens
pH 6.0, 22°C
0.00049
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol
Homo sapiens
pH 6.0, 22°C
0.00029
5-(benzenesulfonyl)-2-nitrophenol
Homo sapiens
pH 6.0, 22°C
0.00013 - 0.00015
chenodeoxycholic acid
0.0007 - 0.0009
Flufenamic acid
0.0028 - 0.0035
Hexestrol
0.0069 - 0.01
Ibuprofen
0.07 - 0.075
indomethacin
0.00007 - 0.00008
lithocholic acid
0.0016 - 0.0017
Medroxyprogesterone acetate
0.012 - 0.018
Phenolphthalein
0.00006 - 0.00008
Ursodeoxycholic acid
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues
Manually annotated by BRENDA team
additional information
in addition to neurons, 3alpha-HSOR activity appears to be highly localized in glial cells, such as type 1 astrocytes in culture and oligodendrocytes, although, 3alpa-HSOR activity has not been detected in myelin membranes of the CNS
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme belongs to the AKR1C subfamily, the members of which catalyze the reduction of ketosteroids and ketoprostaglandins
metabolism
human aldo-keto reductases (AKR1C1-AKR1C4, AKR1Cs) play an important role in the intracellular metabolism of steroids. All AKR1Cs have both 3alpha- and 3beta-HSD activities, AKR1C2 and AKR1C4 have a higher 3alpha-HSD activity, whereas AKR1C1 and AKR1C3 have a higher 3beta-HSD activity
physiological function
evolution
malfunction
metabolism
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
AK1C3_HUMAN
323
0
36853
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
-
x * 36000, SDS-PAGE
36790
calculated from predicted DD2 amino acid sequence of 322 residues
36850
calculated from predicted DD4 amino acid sequence of 321 residues
37000
purified DD2
39000
purified DD4
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 37000, recombinant AKR1C1, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme in ternary complex with NADP+ and one inhibitor, from inhibitors 1-6, 15 mg/ml protein in 10 mM potassium phosphate pH 7.4, 500 mM NaCl, 1 mM ethylenediaminetetraacetic acid, 1 mM dithiothreitol is mixed with crystallization solution containing 0.1 M sodium citrate, pH 5.5, 0.4 M ammonium acetate, 2.5% v/v 2-methyl-2,4-pentanediol, 22-30% w/v PEG 4000 for inhibitors 1-4, and containing 0.1 M HEPES pH 6.5, 0.2 M ammonium dihydrogen phosphate, 20-25% w/v PEG 3350 for inhibitors 5 and 6, X-ray diffraction structure determination analysis at 1.55-2.81 A resolution, modelling
3alpha-HSD3-NADP+-progesterone complex and 3alpha-HSD3 mutant V54L-NADP+-progesterone complex, sitting drop vapor diffusion method, room temperature, the reservoir solution contains 100 mM sodium cacodylate, pH 6.0, 200 mM ammonium sulfate, 24-26% w/v PEG 3350, with 0.8 mM progesterone, 3-14 days, X-ray diffraction structure determination and analysis at 2.0-2.2 A resolution, molecular replacement with search model, PDB ID 1J96. Progesterone adopts two different binding modes to form complexes within the wild-type enzyme, with one binding mode similar to the orientation of a bile acid (ursodeoxycholate) in the reported ternary complex of human 3alpha-HSD3-NADP+-ursodeoxycholate and the other binding mode resembling the orientation of 20alpha-OHProg in the ternary complex of human 20alpha-HSD-NADP+-20alpha-OHProg
crystal structure determination and analysis of human 3alpha-HSD3-NADP+-5alpha-androstane-3,17-dione/epiandrosterone complex, which was obtained by co-crystallization with 5alpha-DHT in the presence of NADP+. Although 5alpha-DHT is introduced during the crystallization, oxidoreduction of 5alpha-DHT occurs. The locations of 5alpha-androstane-3,17-dione and epiandrosterone are identified in the steroid-binding sites of two 3alpha-HSD3 molecules per crystal asymmetric unit. 5alpha-androstane-3,17-dione and epiandrosterone are oriented upside-down and flipped relative to each other, providing structural clues for 5alpha-DHT reverse binding in the enzyme with the generation of different products. determination and analysis of human 3alpha-HSD3-NADP+-4-androstene-3,17-dione complex crystal structure
crystal structure of the human 3alpha-HSD type 3 in the ternary complex with testosterone and NADP+ determined by molecular replacement method using the program EPMR, at 1.25-A resolution, binding site analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H216F
-
the mutation decreases 3fold the Km for NADP+. The kinetic constants for bile acids with a 12alpha-hydroxy group are decreased 1.5-7fold and those for the other substrates are increased 1.3-9fold. The mutation decreases the stimulatory effects of the enzyme activity by sulfobromophthalein, clofibric acid and thyroxine, which increases the Km for the coenzyme and substrate of the mutant enzymes more highly than those of the wild type enzyme
H216L
-
inactive
H216W
-
inactive
H216Y
-
the mutation decreases 3fold the Km for NADP+. The kinetic constants for bile acids with a 12alpha-hydroxy group are decreased 1.5-7fold and those for the other substrates are increased 1.3-9fold. The mutation decreases the stimulatory effects of the enzyme activity by sulfobromophthalein, clofibric acid and thyroxine, which increases the Km for the coenzyme and substrate of the mutant enzymes more highly than those of the wild type enzyme
V54L
site-directed mutagenesis, the change renders the sequence identical to that of human 20-alpha hydroxysteroid dehydrogenase. The V54L mutation directly restricts the steroid binding modes to a unique one, which resembles the orientation of 20alpha-OHProg within human 20alpha-HSD. The kinetic study shows that the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of 5alpha-dihydrotestosterone, while this mutation enhances the 20alpha-HSD activity to convert progesterone
additional information
when a specific siRNA is used to suppress 3alpha-HSD3 expression without interfering with 3alpha-HSD4, which shares a highly homologous active site, the 5alpha-DHT concentration increases, whereas MCF-7 cell growth is suppressed. Downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, gel fitration, and ultrafiltration
recombinant enzyme from Escherichia coli strain BL21(DE3)
recombinant His-tagged AKR1C3 from Escherichia coli strain BL21
Q-Sepharose column chromatography and Sephadex G-100 gel filtration
-
recombinant enzyme from Escherichia coli strain BL21(DE3)
recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by glutathione affinity chromatography, cleavage of the tag by thrombin, and anion exchange chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
AKR1C3, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
overexpression in Escherichia coli
recombinant expression in mouse PCa cells and of FLAG-AKR1C3 in mouse Rv1 cells, recombinant expression of His-tagged AKR1C3 in Escherichia coli strain BL21
recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
AKR1C1, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
AKR1C2, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
AKR1C4, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
expressed in COS-1 cells, PC-3 cells, and LNCaP cells
-
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli cells
-
expressed in Escherichia coli JM109 cells
-
expressed in Huh-7 and Hep-G2 cells
-
overexpression in Escherichia coli
overexpression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
R1881 treatment decreases AKR1C3 transcripts by about 1.5fold in Rv1 cells, AKR1C3 transcripts are androgen-repressed
liver X receptor alpha binds specifically to the liver X receptor alpha response element and mediates transcriptional activation of the AKR1C4 gene. Liver X receptor ligand T1317 induces isoform AKR1C4 expression approximately 2.3fold
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. High-throughput inhibitor screening, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Trauger, J.W.; Jiang, A.; Stearns, B.A.; LoGrasso, P.V.
Kinetics of allopregnanolone formation catalyzed by human 3alpha-hydroxysteroid dehydrogenase type III (AKR1C2)
Biochemistry
41
13451-13459
2002
Homo sapiens (P52895), Homo sapiens
Manually annotated by BRENDA team
Stayrook, K.R.; Rogers, P.M.; Savkur, R.S.; Wang, Y.; Su, C.; Varga, G.; Bu, X.; Wei, T.; Nagpal, S.; Liu, X.S.; Burris, T.P.
Regulation of human 3 alpha-hydroxysteroid dehydrogenase (AKR1C4) expression by the liver X receptor alpha
Mol. Pharmacol.
73
607-612
2008
Homo sapiens
Manually annotated by BRENDA team
Deyashiki, Y.; Ogasawara, A.; Nakayama, T.; Nakanishi, M.; Miyabe, Y.; Sato, K.; Hara, A.
Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder
Biochem. J.
299
545-552
1994
Homo sapiens (P17516), Homo sapiens (P52895)
Manually annotated by BRENDA team
Shiraishi, H.; Ishikura, S.; Matsuura, K.; Deyashiki, Y.; Ninomiya, M.; Sakai, S.; Hara, A.
Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA
Biochem. J.
334
399-405
1998
Homo sapiens
Manually annotated by BRENDA team
Penning, T.; Burczynski, M.; Jez, J.; Hung, C.; Lin, H.; Ma, H.; Moore, M.; Palackal, N.; Ratnam, K.
Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: Functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones
Biochem. J.
351
67-77
2000
Homo sapiens (P17516), Homo sapiens
Manually annotated by BRENDA team
Ohta, T.; Ishikura, S.; Shintani, S.; Usami, N.; Hara, A.
Kinetic alteration of a human dihydrodiol/3alpha-hydroxysteroid dehydrogenase isoenzyme, AKR1C4, by replacement of histidine-216 with tyrosine or phenylalanine
Biochem. J.
352
685-691
2000
Homo sapiens
Manually annotated by BRENDA team
Rizner, T.; Lin, H.; Penning, T.
Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells
Chem. Biol. Interact.
143-144
401-409
2003
Homo sapiens
Manually annotated by BRENDA team
Khanna, M.; Qin, K.N.; Wang, R.W.; Cheng, K.C.
Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 ?-hydroxysteroid dehydrogenases
J. Biol. Chem.
270
20162-20168
1995
Homo sapiens (P17516), Homo sapiens (P42330)
Manually annotated by BRENDA team
Nahoum, V.; Gangloff, A.; Legrand, P.; Zhu, D.W.; Cantin, L.; Zhorov, B.S.; Luu-The, V.; Labrie, F.; Breton, R.; Lin, S.X.
Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution
J. Biol. Chem.
276
42091-42098
2001
Homo sapiens (P52895)
Manually annotated by BRENDA team
Amano, Y.; Yamaguchi, T.; Niimi, T.; Sakashita, H.
Structures of complexes of type 5 17beta-hydroxysteroid dehydrogenase with structurally diverse inhibitors: insights into the conformational changes upon inhibitor binding
Acta Crystallogr. Sect. D
71
918-927
2015
Homo sapiens (P42330)
Manually annotated by BRENDA team
Zhang, B.; Hu, X.; Wang, X.; Theriault, J.; Zhu, D.; Shang, P.; Labrie, F.; Lin, S.
Human 3alpha-hydroxysteroid dehydrogenase type 3: structural clues of 5alpha-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth
Biochem. J.
473
1037-1046
2016
Homo sapiens (P52895)
Manually annotated by BRENDA team
Fan, L.; Peng, G.; Hussain, A.; Fazli, L.; Guns, E.; Gleave, M.; Qi, J.
The steroidogenic enzyme AKR1C3 regulates stability of the ubiquitin ligase Siah2 in prostate cancer cells
J. Biol. Chem.
290
20865-20879
2015
Homo sapiens (P42330)
Manually annotated by BRENDA team
Zhang, B.; Zhu, D.W.; Hu, X.J.; Zhou, M.; Shang, P.; Lin, S.X.
Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3) the V54L mutation restricting the steroid alternative binding and enhancing the 20?-HSD activity
J. Steroid Biochem. Mol. Biol.
141
135-143
2014
Homo sapiens (Q04828)
Manually annotated by BRENDA team
Wan, R.; Kong, X.; Yang, Y.; Tao, S.; Chen, Y.; Teichmann, A.T.; Wieland, F.H.
Role of human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C3) in the extrahepatic metabolism of the steroidal aromatase inactivator Formestane
J. Steroid Biochem. Mol. Biol.
198
105527
2020
Homo sapiens (P17516), Homo sapiens (P42330), Homo sapiens (P52895), Homo sapiens (Q04828)
Manually annotated by BRENDA team
Giatti, S.; Diviccaro, S.; Falvo, E.; Garcia-Segura, L.; Melcangi, R.
Physiopathological role of the enzymatic complex 5alpha-reductase and 3alpha/beta-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites
Front. Neuroendocrinol.
57
100836
2020
Homo sapiens (Q04828), Mus musculus (Q91WT7), Rattus norvegicus (P23457)
Manually annotated by BRENDA team