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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
  • Androstenedione Metabolism
  • Apparent mineralocorticoid excess syndrome
  • Aromatase deficiency
  • 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
  • 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 → Cortisol + 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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  3. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. [PubMed:12690205 ]
  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 ]
  7. Lemonde HA, Custard EJ, Bouquet J, Duran M, Overmars H, Scambler PJ, Clayton PT: Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure in infancy. Gut. 2003 Oct;52(10):1494-9. [PubMed:12970144 ]
  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 ]