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Identification
HMDB Protein ID HMDBP00550
Secondary Accession Numbers
  • 5822
  • HMDBP06124
Name 3-oxo-5-beta-steroid 4-dehydrogenase
Synonyms
  1. Aldo-keto reductase family 1 member D1
  2. Delta(4)-3-ketosteroid 5-beta-reductase
  3. Delta(4)-3-oxosteroid 5-beta-reductase
Gene Name AKR1D1
Protein Type Enzyme
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one can also act as substrates.
Pathways
  • 11-beta-hydroxylase deficiency (CYP11B1)
  • 17-alpha-hydroxylase deficiency (CYP17)
  • 17-Beta Hydroxysteroid Dehydrogenase III Deficiency
  • 21-hydroxylase deficiency (CYP21)
  • 27-Hydroxylase Deficiency
  • 3-Beta-Hydroxysteroid Dehydrogenase Deficiency
  • Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency
  • Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency
  • Androgen and Estrogen Metabolism
  • Apparent mineralocorticoid excess syndrome
  • Aromatase deficiency
  • Bile Acid Biosynthesis
  • Cerebrotendinous Xanthomatosis (CTX)
  • Congenital Bile Acid Synthesis Defect Type II
  • Congenital Bile Acid Synthesis Defect Type III
  • Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH
  • Corticosterone methyl oxidase I deficiency (CMO I)
  • Corticosterone methyl oxidase II deficiency - CMO II
  • Familial Hypercholanemia (FHCA)
  • Primary bile acid biosynthesis
  • Steroid hormone biosynthesis
  • Steroidogenesis
  • Zellweger Syndrome
Reactions
5-beta-Cholestan-3-one + NADP → Cholestenone + NADPH details
17a,21-Dihydroxy-5b-pregnane-3,11,20-trione + NADP → Cortisone details
Etiocholanedione + NADP → Hydrogen Ion + NADPH + Androstenedione details
5a-Pregnane-3,20-dione + Acceptor → Progesterone + Reduced acceptor details
Progesterone + NADPH + Hydrogen Ion → 5a-Pregnane-3,20-dione + NADP details
5b-Dihydrotestosterone + NADP → Testosterone + NADPH + Hydrogen Ion details
Dihydrocortisol + NADP → Hydrocortisone + NADPH + Hydrogen Ion details
17a,21-Dihydroxy-5b-pregnane-3,11,20-trione + NADP → Cortisone + NADPH + Hydrogen Ion details
11b,21-Dihydroxy-3,20-oxo-5b-pregnan-18-al + NADP → Aldosterone + NADPH + Hydrogen Ion details
7a-Hydroxy-5b-cholestan-3-one + NADP → 7a-Hydroxy-cholestene-3-one + NADPH + Hydrogen Ion details
7a,12a-Dihydroxy-5b-cholestan-3-one + NADP → 7a,12a-Dihydroxy-cholestene-3-one + NADPH + Hydrogen Ion details
GO Classification
Biological Process
bile acid biosynthetic process
digestion
androgen metabolic process
bile acid catabolic process
C21-steroid hormone metabolic process
cholesterol catabolic process
oxidation-reduction process
Cellular Component
cytosol
Function
catalytic activity
oxidoreductase activity
Molecular Function
delta4-3-oxosteroid 5beta-reductase activity
3-oxo-5-beta-steroid 4-dehydrogenase activity
steroid binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 7
Locus 7q32-q33
SNPs AKR1D1
Gene Sequence
>981 bp
ATGGATCTCAGTGCTGCAAGTCACCGCATACCTCTAAGTGATGGAAACAGCATTCCCATC
ATCGGACTTGGTACCTACTCAGAACCTAAATCGACCCCTAAGGGAGCCTGTGCAACATCG
GTGAAGGTTGCTATTGACACAGGGTACCGACATATTGATGGGGCCTACATCTACCAAAAT
GAACACGAAGTTGGGGAGGCCATCAGGGAGAAGATAGCAGAAGGAAAGGTGCGGAGGGAA
GATATCTTCTACTGTGGAAAGCTATGGGCTACAAATCATGTCCCAGAGATGGTCCGCCCA
ACCCTGGAGAGGACACTCAGGGTCCTCCAGCTAGATTATGTGGATCTTTACATCATTGAA
GTACCCATGGCCTTTAAGCCAGGAGATGAAATATACCCTAGAGATGAGAATGGCAAATGG
TTATATCACAAGTCAAATCTGTGTGCCACTTGGGAGGCGATGGAAGCTTGCAAAGACGCT
GGCTTGGTGAAATCCCTGGGAGTGTCCAATTTTAACCGCAGGCAGCTGGAGCTCATCCTG
AACAAGCCAGGACTCAAACACAAGCCAGTCAGCAACCAGGTTGAGTGCCATCCGTATTTC
ACCCAGCCAAAACTCTTGAAATTTTGCCAACAACATGACATTGTCATTACTGCATATAGC
CCTTTGGGGACCAGTAGGAATCCAATCTGGGTGAATGTTTCTTCTCCACCTTTGTTAAAG
GATGCACTTCTAAACTCATTGGGGAAAAGGTACAATAAGACAGCAGCTCAAATTGTTTTG
CGTTTCAACATCCAGCGAGGGGTGGTTGTCATTCCTAAAAGCTTTAATCTTGAAAGGATC
AAAGAAAATTTTCAGATCTTTGACTTTTCTCTCACTGAAGAAGAAATGAAGGACATTGAA
GCCTTGAATAAAAATGTCCGCTTTGTAGAATTGCTCATGTGGCGCGATCATCCTGAATAC
CCATTTCATGATGAATACTGA
Protein Properties
Number of Residues 326
Molecular Weight 32889.38
Theoretical pI 6.619
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>3-oxo-5-beta-steroid 4-dehydrogenase
MDLSAASHRIPLSDGNSIPIIGLGTYSEPKSTPKGACATSVKVAIDTGYRHIDGAYIYQN
EHEVGEAIREKIAEGKVRREDIFYCGKLWATNHVPEMVRPTLERTLRVLQLDYVDLYIIE
VPMAFKPGDEIYPRDENGKWLYHKSNLCATWEAMEACKDAGLVKSLGVSNFNRRQLELIL
NKPGLKHKPVSNQVECHPYFTQPKLLKFCQQHDIVITAYSPLGTSRNPIWVNVSSPPLLK
DALLNSLGKRYNKTAAQIVLRFNIQRGVVVIPKSFNLERIKENFQIFDFSLTEEEMKDIE
ALNKNVRFVELLMWRDHPEYPFHDEY
GenBank ID Protein 431857
UniProtKB/Swiss-Prot ID P51857
UniProtKB/Swiss-Prot Entry Name AK1D1_HUMAN
PDB IDs
GenBank Gene ID Z28339
GeneCard ID AKR1D1
GenAtlas ID AKR1D1
HGNC ID HGNC:388
References
General References
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  4. Kondo KH, Kai MH, Setoguchi Y, Eggertsen G, Sjoblom P, Setoguchi T, Okuda KI, Bjorkhem I: Cloning and expression of cDNA of human delta 4-3-oxosteroid 5 beta-reductase and substrate specificity of the expressed enzyme. Eur J Biochem. 1994 Jan 15;219(1-2):357-63. [PubMed:7508385 ]
  5. Charbonneau A, The VL: Genomic organization of a human 5beta-reductase and its pseudogene and substrate selectivity of the expressed enzyme. Biochim Biophys Acta. 2001 Jan 26;1517(2):228-35. [PubMed:11342103 ]
  6. Di Costanzo L, Drury JE, Penning TM, Christianson DW: Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis. J Biol Chem. 2008 Jun 13;283(24):16830-9. doi: 10.1074/jbc.M801778200. Epub 2008 Apr 11. [PubMed:18407998 ]
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  8. Gonzales E, Cresteil D, Baussan C, Dabadie A, Gerhardt MF, Jacquemin E: SRD5B1 (AKR1D1) gene analysis in delta(4)-3-oxosteroid 5beta-reductase deficiency: evidence for primary genetic defect. J Hepatol. 2004 Apr;40(4):716-8. [PubMed:15030995 ]