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IUBMB Comments The reaction occurs in the reverse direction with reduction of the terminal double bond next to the alcohol group. Isolated from human fetal brain tissue but present in all eukaryotes. In mammalian cells dolichols are predominantly 18-21 isoprene units in length.
Synonyms
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steroid 5alpha-reductase type 3
SDR5A3
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steroid 5alpha-reductase type 3
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steroid 5alpha-reductase type 3
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ditrans,polycis-dolichol + NADP+ = ditrans,polycis-polyprenol + NADPH + H+
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MetaCyc
dolichol and dolichyl phosphate biosynthesis
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ditrans,polycis-dolichol:NADP+ 2,3-oxidoreductase
The reaction occurs in the reverse direction with reduction of the terminal double bond next to the alcohol group. Isolated from human fetal brain tissue but present in all eukaryotes. In mammalian cells dolichols are predominantly 18-21 isoprene units in length.
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dehydrodolichol + NADPH + H+
dolichol + NADP+
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Substrates: -
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ditrans,polycis-polyprenol + NADPH + H+
ditrans,polycis-dolichol + NADP+
ditrans,polycis-polyprenol-15 + NADPH + H+
ditrans,polycis-dolichol-15 + NADP+
Substrates: -
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ditrans,polycis-polyprenol-16 + NADPH + H+
ditrans,polycis-dolichol-16 + NADP+
Substrates: -
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ditrans,polycis-polyprenol-17 + NADPH + H+
ditrans,polycis-dolichol-17 + NADP+
Substrates: -
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ditrans,polycis-polyprenol + NADPH + H+
ditrans,polycis-dolichol + NADP+
Substrates: -
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ditrans,polycis-polyprenol + NADPH + H+
ditrans,polycis-dolichol + NADP+
Substrates: -
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ditrans,polycis-polyprenol + NADPH + H+
ditrans,polycis-dolichol + NADP+
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Substrates: polyisoprenoids with 13-18 isoprene residues are preferentially reduced
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ditrans,polycis-polyprenol-15 + NADPH + H+
ditrans,polycis-dolichol-15 + NADP+
Substrates: -
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ditrans,polycis-polyprenol-16 + NADPH + H+
ditrans,polycis-dolichol-16 + NADP+
Substrates: -
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ditrans,polycis-polyprenol-17 + NADPH + H+
ditrans,polycis-dolichol-17 + NADP+
Substrates: -
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Breast Neoplasms
Over-expression of SRD5A3 and its prognostic significance in breast cancer.
Cerebellar Ataxia
Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Adult phenotype and further phenotypic variability in SRD5A3-CDG.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null Mutation.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Review of SRD5A3 Disease-Causing Sequence Variants and Ocular Findings in Steroid 5?-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
SRD5A3 defective congenital disorder of glycosylation: clinical utility gene card.
ditrans,polycis-undecaprenyl-diphosphate synthase [(2e,6e)-farnesyl-diphosphate specific] deficiency
SRD5A3-CDG: A patient with a novel mutation.
Eye Diseases
Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3.
Intellectual Disability
Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3.
Malaria
Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.
Neoplasms
A Prognostic Model for Brain Glioma Patients Based on 9 Signature Glycolytic Genes.
Neoplasms
Steroid 5 alpha-reductase 3 (SRD5A3) promotes tumor growth and predicts poor survival of human hepatocellular carcinoma (HCC).
polyprenol reductase deficiency
Life with too much polyprenol: polyprenol reductase deficiency.
polyprenol reductase deficiency
SRD5A3-CDG: A patient with a novel mutation.
Prostatic Neoplasms
Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer.
Prostatic Neoplasms
Role of dutasteride in pre-clinical ETS fusion-positive prostate cancer models.
Retinal Dystrophies
Association of Steroid 5?-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
Vision Disorders
Association of Steroid 5?-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
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UniProt
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Highest Expressing Human Cell Lines
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Cell Line Links
Gene Links
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physiological function
enzyme is necessary for the reduction of the alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation
physiological function
Srd5a3 mutation is lethal in mouse and results in an activation of the unfolded protein response pathway
physiological function
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the activities of yeast cis-prenyltransferases Rer2p and Srt1p and polyprenol reductase are not co-regulated and the reductase may be the rate-limiting enzyme in dolichol synthesis if the amount of polyisoprenoids synthesized exceeds a certain level
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expressed in Nicotiana benthamiana leaves
expression in Saccharomyces cerevisiae and HEK-293T cells
expression in Saccharomyces cerevisiae and HEK-293T cells
expression in Saccharomyces cerevisiae and HEK-293T cells
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medicine
loss of function mutations of the SRD5A3 gene cause a multisystemic syndrome with eye malformations, cerebellar vermis hypoplasia, and psychomotor delay. Plasma from patients shows increased level of polyprenoids
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Szkopinska, A.; Swiezewska, E.; Rytka, J.
Interplay between the cis-prenyltransferases and polyprenol reductase in the yeast Saccharomyces cerevisiae
Biochimie
88
271-276
2006
Saccharomyces cerevisiae
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Cantagrel, V.; Lefeber, D.J.; Ng, B.G.; Guan, Z.; Silhavy, J.L.; Bielas, S.L.; Lehle, L.; Hombauer, H.; Adamowicz, M.; Swiezewska, E.; De Brouwer, A.P.; Bluemel, P.; Sykut-Cegielska, J.; Houliston, S.; Swistun, D.; Ali, B.R.; Dobyns, W.B.; Babovic-Vuksanovic, D.; van Bokhoven, H.; Wevers, R.A.; Raetz, C.
SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder
Cell
142
203-217
2010
Homo sapiens (Q9H8P0), Homo sapiens, Mus musculus (Q9WUP4)
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Sagami, H.; Kurisaki, A.; Ogura, K.
Formation of dolichol from dehydrodolichol is catalyzed by NADPH-dependent reductase localized in microsomes of rat liver
J. Biol. Chem.
268
10109-10113
1993
Rattus norvegicus
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Van Gelder, K.; Virta, L.K.A.; Easlick, J.; Prudhomme, N.; McAlister, J.A.; Geddes-McAlister, J.; Akhtar, T.A.
A central role for polyprenol reductase in plant dolichol biosynthesis
Plant Sci.
303
110773
2021
Solanum lycopersicum (A0A3Q7ETM3), Solanum lycopersicum
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