3-oxo-5-alpha-steroid 4-dehydrogenase 1

Function

Catalyzes the irreversible stereospecific reduction of the delta 4,5 bond (double bond between carbons 4 and 5) of various 3-oxo steroids (3-keto steroids) producing their 5alpha dihydro-3-oxo forms. Converts testosterone into 5-alpha-dihydrotestosterone (DHT), a more potent androgen as it is the preferred ligand for androgen receptor (AR) transactivation, making this reaction a key step in male sexual differentiation during development. Besides testosterone, it can also act on other steroids, including progesterone, androstenedione, and corticoids, producing metabolites with diverse roles. Hence, it plays a central role in sexual differentiation and androgen physiology.

Classification

Family (Pfam)

PF02544 Steroid_dh

InterPro

3-oxo-5-alpha-steroid_4-DH, 3-oxo-5_a-steroid_4-DH_C, SRD5A/TECR

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Gene Ontology · 43

• GO:0070852 cell body fiber
• GO:0005789 endoplasmic reticulum membrane
• GO:0043025 neuronal cell body
• GO:0048471 perinuclear region of cytoplasm
• GO:0047751 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity
• GO:0003865 3-oxo-5-alpha-steroid 4-dehydrogenase activity
• GO:0033218 amide binding
• GO:0009055 electron transfer activity
• GO:0070402 NADPH binding
• GO:0006702 androgen biosynthetic process
• GO:0006710 androgen catabolic process
• GO:0060348 bone development
• GO:0030154 cell differentiation
• GO:0071320 cellular response to cAMP
• GO:0071549 cellular response to dexamethasone stimulus
• GO:0071872 cellular response to epinephrine stimulus
• GO:0071392 cellular response to estradiol stimulus
• GO:0071363 cellular response to growth factor stimulus
• GO:0032869 cellular response to insulin stimulus
• GO:1904015 cellular response to serotonin
• GO:0009267 cellular response to starvation
• GO:0071394 cellular response to testosterone stimulus
• GO:0021987 cerebral cortex development
• GO:0016101 diterpenoid metabolic process
• GO:0030540 female genitalia development
• GO:0021766 hippocampus development
• GO:0021854 hypothalamus development
• GO:0001889 liver development
• GO:0030539 male genitalia development
• GO:0008584 male gonad development
• GO:0021983 pituitary gland development
• GO:0042448 progesterone metabolic process
• GO:0043627 response to estrogen
• GO:0032354 response to follicle-stimulating hormone
• GO:0060992 response to fungicide
• GO:0060416 response to growth hormone
• GO:0014850 response to muscle activity
• GO:1904638 response to resveratrol
• GO:0009410 response to xenobiotic stimulus
• GO:0007530 sex determination
• GO:0021510 spinal cord development
• GO:0021794 thalamus development
• GO:0001655 urogenital system development

Drugs targeting this protein · 2

• DUTASTERIDE inhibitor
• ABIRATERONE inhibitor

Related proteins · sequence + function similarity

• 3-oxo-5-alpha-steroid 4-dehydrogenase 1 0.99
• 3-oxo-5-alpha-steroid 4-dehydrogenase 1 0.95
• 3-oxo-5-alpha-steroid 4-dehydrogenase 1 0.89
• 3-oxo-5-alpha-steroid 4-dehydrogenase 1 0.88
• 3-oxo-5-alpha-steroid 4-dehydrogenase 2 0.84
• 3-oxo-5-alpha-steroid 4-dehydrogenase 2 0.83
• 3-oxo-5-alpha-steroid 4-dehydrogenase 2 0.83
• Protein DEETIOLATED 2 0.83
• 3-oxo-5-alpha-steroid 4-dehydrogenase 2 0.81
• 3-oxo-5-alpha-steroid 4-dehydrogenase 2 0.81
• Polyprenal reductase 2 0.77
• Polyprenal reductase 1 0.76

Co-cited proteins · studied together in the literature

• 3-oxo-5-alpha-steroid 4-dehydrogenase 1 1 shared papers
• 3-oxo-5-alpha-steroid 4-dehydrogenase 2 1 shared papers
• 11-beta-hydroxysteroid dehydrogenase type 2 1 shared papers
• Cytochrome P450 11B2, mitochondrial 1 shared papers
• 11-beta-hydroxysteroid dehydrogenase 1 1 shared papers
• Cytochrome P450 11B1, mitochondrial 1 shared papers

Literature · 8 cited papers

• 11beta-hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5alpha-reductase yielding 11beta-hydroxy-5alpha-androstanedione. J. Steroid Biochem. Mol. Biol. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• New steroid 5alpha-reductase type I (SRD5A1) homologous sequences on human chromosomes 6 and 8. Pflugers Arch. · 2001
• Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. Proc. Natl. Acad. Sci. U.S.A. · 2000
• Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases. Proc. Natl. Acad. Sci. U.S.A. · 1990
• Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue. Genomics · 1991