BRENDA - Enzyme Database show
show all sequences of 1.1.1.178

A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival

Rauschenberger, K.; Schoeler, K.; Sass, J.O.; Sauer, S.; Djuric, Z.; Rumig, C.; Wolf, N.I.; Okun, J.G.; Koelker, S.; Schwarz, H.; Fischer, C.; Grziwa, B.; Runz, H.; Nuemann, A.; Shafqat, N.; Kavanagh, K.L.; Haemmerling, G.; Wanders, R.J.; Shield, J.P.; Wendel, U.; Stern, D.; Nawroth, P.; Hoffmann, G.F.; Bartram, C.R.; EMBO Mol. Med. 2, 51-62 (2010)

Data extracted from this reference:

Application
Application
Commentary
Organism
medicine
mutation p.D86G c.257A>G in exon 3 was diagnosed in one child with a very severe neonatal presentation, absent neurological development and death from progressive hypertrophic cardiomyopathy at the age of 7 months. MHBD activity in fibroblasts was only partially reduced to approximately 30% of normal. Mutation p.Q165H c.495A>C in exon 5 was diagnosed in a boy who presented with pre- and postnatal failure to thrive but normal cognitive and motor development. Neurological examination in this boy and two affected relatives has been entirely normal up to the present age of 8 years. There is no measurable MHBD activity in fibroblasts, molecular studies identified hemizygosity for the mutation. There is no correlation between enzyme activity and clinical presentation. HSD10 is essential for structural and functional integrity of mitochondria independently of its enzymatic activity. Impairment of this function in neural cells causes apoptotic cell death whilst the enzymatic activity of HSD10 is not required for cell survival
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
D86G
28% residual activity. Mutation causes severe disruption of mitochondrial morphology
Homo sapiens
additional information
mutation p.D86G c.257A>G in exon 3 was diagnosed in one child with a very severe neonatal presentation, absent neurological development and death from progressive hypertrophic cardiomyopathy at the age of 7 months. MHBD activity in fibroblasts was only partially reduced to approximately 30% of normal. Mutation p.Q165H c.495A>C in exon 5 was diagnosed in a boy who presented with pre- and postnatal failure to thrive but normal cognitive and motor development. Neurological examination in this boy and two affected relatives has been entirely normal up to the present age of 8 years. There is no measurable MHBD activity in fibroblasts, molecular studies identified hemizygosity for the mutation
Homo sapiens
Q165H
complete loss of activity, no binding of cofactor NAD+ or NADH
Homo sapiens
R130C
64% residual activity, mutant is unstable at room temperature and steadily loses enzyme activity. Mutation causes severe disruption of mitochondrial morphology
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
mitochondrion
-
Homo sapiens
5739
-
mitochondrion
-
Mus musculus
5739
-
mitochondrion
-
Xenopus laevis
5739
-
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q99714
bifunctional 17beta-hydroxysteroid dehydrogenase type 10/2-methyl-3-hydroxybutyryl-CoA dehydrogenase
-
Mus musculus
-
bifunctional 17beta-hydroxysteroid dehydrogenase type 10/2-methyl-3-hydroxybutyryl-CoA dehydrogenase
-
Xenopus laevis
-
bifunctional 17beta-hydroxysteroid dehydrogenase type 10/2-methyl-3-hydroxybutyryl-CoA dehydrogenase
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
fibroblast
-
Homo sapiens
-
fibroblast
-
Mus musculus
-
fibroblast
-
Xenopus laevis
-
Application (protein specific)
Application
Commentary
Organism
medicine
mutation p.D86G c.257A>G in exon 3 was diagnosed in one child with a very severe neonatal presentation, absent neurological development and death from progressive hypertrophic cardiomyopathy at the age of 7 months. MHBD activity in fibroblasts was only partially reduced to approximately 30% of normal. Mutation p.Q165H c.495A>C in exon 5 was diagnosed in a boy who presented with pre- and postnatal failure to thrive but normal cognitive and motor development. Neurological examination in this boy and two affected relatives has been entirely normal up to the present age of 8 years. There is no measurable MHBD activity in fibroblasts, molecular studies identified hemizygosity for the mutation. There is no correlation between enzyme activity and clinical presentation. HSD10 is essential for structural and functional integrity of mitochondria independently of its enzymatic activity. Impairment of this function in neural cells causes apoptotic cell death whilst the enzymatic activity of HSD10 is not required for cell survival
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
D86G
28% residual activity. Mutation causes severe disruption of mitochondrial morphology
Homo sapiens
additional information
mutation p.D86G c.257A>G in exon 3 was diagnosed in one child with a very severe neonatal presentation, absent neurological development and death from progressive hypertrophic cardiomyopathy at the age of 7 months. MHBD activity in fibroblasts was only partially reduced to approximately 30% of normal. Mutation p.Q165H c.495A>C in exon 5 was diagnosed in a boy who presented with pre- and postnatal failure to thrive but normal cognitive and motor development. Neurological examination in this boy and two affected relatives has been entirely normal up to the present age of 8 years. There is no measurable MHBD activity in fibroblasts, molecular studies identified hemizygosity for the mutation
Homo sapiens
Q165H
complete loss of activity, no binding of cofactor NAD+ or NADH
Homo sapiens
R130C
64% residual activity, mutant is unstable at room temperature and steadily loses enzyme activity. Mutation causes severe disruption of mitochondrial morphology
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
mitochondrion
-
Homo sapiens
5739
-
mitochondrion
-
Mus musculus
5739
-
mitochondrion
-
Xenopus laevis
5739
-
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
fibroblast
-
Homo sapiens
-
fibroblast
-
Mus musculus
-
fibroblast
-
Xenopus laevis
-
General Information
General Information
Commentary
Organism
physiological function
generation of conditional Hsd17b10 knock-out mouse lines by elimination of Hsd17b10 in endothelial cells and cells of the immune system. These mice are viable and fertile, but have defects in spleen and vasculature. The animals die rapidly around week 25. Conditional knock-out lines with elimination of the Hsd17b10 gene in noradrenergic neurons are viable and fertile but die around week 26. In the loci coerulei of HSD10 deficient mice in noradrenergic neurons, almost 30% of the mitochondria show depletion of cristae and appeared empty, more than 50% of the mitochondria are loosely packed and have swollen cristae, while normal morphology is only found in 20%
Mus musculus
physiological function
enzyme knock-down by antisense-oligonucleotides results in a 40% reduction in pyruvate turnover compared to the uninjected or control injected tissue. The morphology of mitochondria in animal cap explants is changed after HSD10 knock-down. Mitochondria show severe reduction of cristae and a generally irregular shape
Xenopus laevis
General Information (protein specific)
General Information
Commentary
Organism
physiological function
generation of conditional Hsd17b10 knock-out mouse lines by elimination of Hsd17b10 in endothelial cells and cells of the immune system. These mice are viable and fertile, but have defects in spleen and vasculature. The animals die rapidly around week 25. Conditional knock-out lines with elimination of the Hsd17b10 gene in noradrenergic neurons are viable and fertile but die around week 26. In the loci coerulei of HSD10 deficient mice in noradrenergic neurons, almost 30% of the mitochondria show depletion of cristae and appeared empty, more than 50% of the mitochondria are loosely packed and have swollen cristae, while normal morphology is only found in 20%
Mus musculus
physiological function
enzyme knock-down by antisense-oligonucleotides results in a 40% reduction in pyruvate turnover compared to the uninjected or control injected tissue. The morphology of mitochondria in animal cap explants is changed after HSD10 knock-down. Mitochondria show severe reduction of cristae and a generally irregular shape
Xenopus laevis
Other publictions for EC 1.1.1.178
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)
725097
Yang
A 5-methylcytosine hotspot res ...
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380-384
2013
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A non-enzymatic function of 17 ...
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EMBO Mol. Med.
2
51-62
2010
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697369
Garcia-Villoria
Study of patients and carriers ...
Homo sapiens
Clin. Biochem.
42
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2009
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670477
Garcia-Villoria
2-Methyl-3-hydroxybutyryl-CoA ...
Homo sapiens
Pediatr. Res.
58
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2005
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4
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286123
Zschocke
Progressive infantile neurodeg ...
Homo sapiens
Pediatr. Res.
48
852-855
2000
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2
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2
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286122
Luo
Short-chain 3-hydroxy-2-methyl ...
Rattus norvegicus
Arch. Biochem. Biophys.
321
214-220
1995
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286121
Gibson
A coupled assay detecting defe ...
Homo sapiens
Clin. Chim. Acta
205
127-135
1992
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1
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286120
Conrad R.S.; Massey L.K.; Sokatch J.R.
D- and L-leucine metabolism an ...
Pseudomonas putida, Pseudomonas putida PpG2
J. Bacteriol.
4
103-111
1974
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