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Information on EC 1.1.1.149 - 20alpha-hydroxysteroid dehydrogenase and Organism(s) Mus musculus and UniProt Accession Q8K023

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IUBMB Comments
Re-specific with respect to NAD(P)+ (cf. EC 1.1.1.62 17beta-estradiol 17-dehydrogenase).
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This record set is specific for:
Mus musculus
UNIPROT: Q8K023
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
akr1c3, akr1c1, 20alpha-hsd, 20alpha-hydroxysteroid dehydrogenase, 20beta-hydroxysteroid dehydrogenase, akr1c9, akr1c14, 3alpha-hsor, 3alpha-hydroxysteroid oxidoreductase, aldo-keto reductase family 1 member c1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20alpha-HSD
-
20-alpha-HSD
-
-
-
-
20alpha-HSD
20alpha-HSDH
-
-
-
-
20alpha-hydroxy steroid dehydrogenase
-
-
-
-
20alpha-hydroxysteroid dehydrogenase
-
-
-
-
20alpha-hydroxysteroid oxidoreductase
-
-
-
-
20alpha-OH-SDH
-
-
-
-
3alpha-HSOR
-
3alpha-hydroxysteroid oxidoreductase
-
HSD1
-
-
-
-
additional information
see also EC 1.1.1.357
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
20alpha-hydroxysteroid:NAD(P)+ 20-oxidoreductase
Re-specific with respect to NAD(P)+ (cf. EC 1.1.1.62 17beta-estradiol 17-dehydrogenase).
CAS REGISTRY NUMBER
COMMENTARY hide
9040-08-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
11-deoxycorticosterone + NAD(P)H
4-pregnen-20alpha,21-diol-3-one + NAD(P)+
show the reaction diagram
-
-
-
-
?
17alpha-hydroxyprogesterone + NAD(P)H
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
show the reaction diagram
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
-
-
-
r
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
show the reaction diagram
reaction of EC 1.1.1.357
-
-
r
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
maternal and fetal 20alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses
-
-
?
additional information
?
-
-
pregnancy induces X-zone regression and abolishes 20alphaHSD expression, which is partially restored in animals that are kept from nursing their pups, lactation inhibits enzyme expression, X-zone regulation, overview
-
-
?
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
17alpha-hydroxyprogesterone + NAD(P)H
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
show the reaction diagram
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
-
-
-
r
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
show the reaction diagram
reaction of EC 1.1.1.357
-
-
r
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
maternal and fetal 20alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses
-
-
?
additional information
?
-
-
pregnancy induces X-zone regression and abolishes 20alphaHSD expression, which is partially restored in animals that are kept from nursing their pups, lactation inhibits enzyme expression, X-zone regulation, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)H
NADH
-
-
NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-naphthoquinone
-
0.01 mM, 55% inhibition of enzyme in liver, 10% in kidney, 10% in lung cytosolic fraction, respectively
9,10-phenanthrenequinone
-
0.01 mM, 70% inhibition of enzyme in liver, 5% in kidney, 60% in lung cytosolic fraction, respectively
apigenin
Bromophenol blue
-
little effect on hepatic NADPH-dependent 20alpha-hydroxysteroid dehydrogenase, moderate inhibitor of hepatic NADH-dependent 20alpha-hydroxysteroid dehydrogenase activity
fisetin
kaempferol
luteolin
myricetin
-
0.02 mM, 60% inhibition of enzyme in liver cytosolic fraction, 0.05 mM, 10% inhibition in kidney cytosolic fraction
naringenin
quercetin
Sulfobromophthalein
-
little effect on hepatic NADPH-dependent 20alpha-hydroxysteroid dehydrogenase, potent inhibitor of hepatic NADH-dependent 20alpha-hydroxysteroid dehydrogenase activity
additional information
-
pregnancy induces X-zone regression and abolishes 20alphaHSD expression, which is partially restored in animals that are kept from nursing their pups
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
enzyme expression is induced by interleukin-2 and interleukin-3 in thymocytes and bone marrow cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0033
11-deoxycorticosterone
-
pH 7.4, 37°C
0.0058
17alpha-hydroxyprogesterone
-
pH 7.4, 37°C
additional information
additional information
-
kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
renal NADH-dependent 20alpha-hydroxysteroid dehydrogenase
6.5
-
hepatic NADPH-dependent 20alpha-hydroxysteroid dehydrogenase
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
Uniprot
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
transcripts of galectin-3 are restricted to corpus luteum and always coincident to the expression of 20alpha-hydroxysteroid dehydrogenase. In the nonpregnant ovary, signals for both galectin-1 and -3 are intense in the old, regressing corpora lutea formed at previous estrous cycles. In the newly formed corpora lutea, the signal intensity of galectin-1 first increases at the starting point of regression followed by increasing galectin-3/20alpha-hydroxysteroid dehydrogenase expressions. Under gestation with active progesterone production, signals for both galectin-1 and -3 in corpora lutea completely disappear. At the perinatal stage, intense expressions of galectin-3/20alpha-hydroxysteroid dehydrogenase recover in the remaining corpora lutea of gestation with the temporal expression of galectin-1 and continue until weaning
Manually annotated by BRENDA team
the protein is strongly detected in the placenta on days 14, 16, and 18 of pregnancy
Manually annotated by BRENDA team
the enzyme is specifically localized in the seminiferous tubule at 8 week
Manually annotated by BRENDA team
immature testis
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
analysis of 3alpha-HSOR mRNA distribution in the mouse brain by in situ hybridization has shown that this enzyme is co-localized with 5alpha-R type 1 in neurons of the cerebral cortex, hippocampus, olfactory bulb, amygdala and thalamus. And 3alpha-HSOR immunoreactivity is largely distributed in both white and gray matters
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
3alpha-HSOR is a member of the aldo-keto reductase superfamily
malfunction
the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Changes in brain levels of PROG metabolites have been detected in Alzheimer's disease (AD) mouse models, such as the 3xTg-AD mouse
metabolism
the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone and testosterone into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview
physiological function
the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone and testosterone formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by progesterone and testosterone. The reduced metabolites of progesterone are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
AKC1H_MOUSE
323
0
37177
Swiss-Prot
other Location (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 37000, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the protein is detected in the testes 1 week after birth and increases dramatically at 8 weeks
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
the enzyme is a marker for the murine X-zone
environmental protection
-
diesel exhaust components are inhibitory on 20alpha-hydroxysteroid dehydrogenase in liver and lung cytosol, with little inhibition in kidney cytosol
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hershkovitz, L.; Beuschlein, F.; Klammer, S.; Krup, M.; Weinstein, Y.
Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone
Endocrinology
148
976-988
2006
Mus musculus, Mus musculus BALB/c
Manually annotated by BRENDA team
Shimada, H.; Miura, K.; Imamura, Y.
Characteristics and inhibition by flavonoids of 20alpha-hydroxysteroid dehydrogenase activity in mouse tissues
Life Sci.
78
2931-2936
2006
Mus musculus
Manually annotated by BRENDA team
Piekorz, R.P.; Gingras, S.; Hoffmeyer, A.; Ihle, J.N.; Weinstein, Y.
Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20alpha-hydroxysteroid dehydrogenase
Mol. Endocrinol.
19
431-440
2005
Mus musculus
Manually annotated by BRENDA team
Shimada, H.; Ohtaguro, M.; Miura, K.; Imamura, Y.
Inhibitory effects of diesel exhaust components and flavonoids on 20alpha-hydroxysteroid dehydrogenase activity in mouse tissues
J. Enzyme Inhib. Med. Chem.
22
445-449
2007
Mus musculus
Manually annotated by BRENDA team
Nio, J.; Iwanaga, T.
Galectins in the mouse ovary: concomitant expression of galectin-3 and progesterone degradation enzyme (20alpha-HSD) in the corpus luteum
J. Histochem. Cytochem.
55
423-432
2007
Mus musculus (Q8K023), Mus musculus
Manually annotated by BRENDA team
Ishida, M.; Choi, J.H.; Hirabayashi, K.; Matsuwaki, T.; Suzuki, M.; Yamanouchi, K.; Horai, R.; Sudo, K.; Iwakura, Y.; Nishihara, M.
Reproductive phenotypes in mice with targeted disruption of the 20alpha-hydroxysteroid dehydrogenase gene
J. Reprod. Dev.
53
499-508
2007
Mus musculus
Manually annotated by BRENDA team
Imamura, Y.; Ohtaguro, M.; Shimada, H.
Several distinct enzymes catalyze 20alpha-hydroxysteroid dehydrogenase activity in mouse liver and kidney
J. Steroid Biochem. Mol. Biol.
107
120-126
2007
Mus musculus
Manually annotated by BRENDA team
Choi, J.H.; Ishida, M.; Matsuwaki, T.; Yamanouchi, K.; Nishihara, M.
Involvement of 20alpha-hydroxysteroid dehydrogenase in the maintenance of pregnancy in mice
J. Reprod. Dev.
54
408-412
2008
Mus musculus
Manually annotated by BRENDA team
Yoo, M.H.; Park, C.W.; Byambaragchaa, M.; Kang, M.H.; Min, K.S.
Data on the localization of EGFP and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) in the placenta and testes of transgenic mice
Data Brief
19
632-637
2018
Mus musculus (Q8K023)
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
Rattus norvegicus, Homo sapiens (Q04828), Mus musculus (Q91WT7)
Manually annotated by BRENDA team