3-oxo-5-beta-steroid 4-dehydrogenase

Details

Name
3-oxo-5-beta-steroid 4-dehydrogenase
Synonyms
  • 1.3.1.3
  • Aldo-keto reductase family 1 member D1
  • Delta(4)-3-ketosteroid 5-beta-reductase
  • Delta(4)-3-oxosteroid 5-beta-reductase
  • SRD5B1
Gene Name
AKR1D1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006946|3-oxo-5-beta-steroid 4-dehydrogenase
MDLSAASHRIPLSDGNSIPIIGLGTYSEPKSTPKGACATSVKVAIDTGYRHIDGAYIYQN
EHEVGEAIREKIAEGKVRREDIFYCGKLWATNHVPEMVRPTLERTLRVLQLDYVDLYIIE
VPMAFKPGDEIYPRDENGKWLYHKSNLCATWEAMEACKDAGLVKSLGVSNFNRRQLELIL
NKPGLKHKPVSNQVECHPYFTQPKLLKFCQQHDIVITAYSPLGTSRNPIWVNVSSPPLLK
DALLNSLGKRYNKTAAQIVLRFNIQRGVVVIPKSFNLERIKENFQIFDFSLTEEEMKDIE
ALNKNVRFVELLMWRDHPEYPFHDEY
Number of residues
326
Molecular Weight
37376.615
Theoretical pI
7.58
GO Classification
Functions
delta4-3-oxosteroid 5beta-reductase activity / steroid binding
Processes
androgen metabolic process / bile acid biosynthetic process / bile acid catabolic process / bile acid metabolic process / C21-steroid hormone metabolic process / cholesterol catabolic process / digestion / oxidation-reduction process / small molecule metabolic process
Components
cytosol / extracellular exosome
General Function
Steroid binding
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0012510|3-oxo-5-beta-steroid 4-dehydrogenase (AKR1D1)
ATGGATCTCAGTGCTGCAAGTCACCGCATACCTCTAAGTGATGGAAACAGCATTCCCATC
ATCGGACTTGGTACCTACTCAGAACCTAAATCGACCCCTAAGGGAGCCTGTGCAACATCG
GTGAAGGTTGCTATTGACACAGGGTACCGACATATTGATGGGGCCTACATCTACCAAAAT
GAACACGAAGTTGGGGAGGCCATCAGGGAGAAGATAGCAGAAGGAAAGGTGCGGAGGGAA
GATATCTTCTACTGTGGAAAGCTATGGGCTACAAATCATGTCCCAGAGATGGTCCGCCCA
ACCCTGGAGAGGACACTCAGGGTCCTCCAGCTAGATTATGTGGATCTTTACATCATTGAA
GTACCCATGGCCTTTAAGCCAGGAGATGAAATATACCCTAGAGATGAGAATGGCAAATGG
TTATATCACAAGTCAAATCTGTGTGCCACTTGGGAGGTTGAGTGCCATCCGTATTTCACC
CAGCCAAAACTCTTGAAATTTTGCCAACAACATGACATTGTCATTACTGCATATAGCCCT
TTGGGGACCAGTAGGAATCCAATCTGGGTGAATGTTTCTTCTCCACCTTTGTTAAAGGAT
GCACTTCTAAACTCATTGGGGAAAAGGTACAATAAGACAGCAGCTCAAATTGTTTTGCGT
TTCAACATCCAGCGAGGGGTGGTTGTCATTCCTAAAAGCTTTAATCTTGAAAGGATCAAA
GAAAATTTTCAGATCTTTGACTTTTCTCTCACTGAAGAAGAAATGAAGGACATTGAAGCC
TTGAATAAAAATGTCCGCTTTGTAGAATTGCTCATGTGGCGCGATCATCCTGAATACCCA
TTTCATGATGAATACTGA
Chromosome Location
7
Locus
7q32-q33
External Identifiers
ResourceLink
UniProtKB IDP51857
UniProtKB Entry NameAK1D1_HUMAN
GenBank Protein ID431857
GenBank Gene IDZ28339
HGNC IDHGNC:388
General References
  1. 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. [Article]
  2. 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. [Article]
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  8. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  9. Faucher F, Cantin L, Luu-The V, Labrie F, Breton R: The crystal structure of human Delta4-3-ketosteroid 5beta-reductase defines the functional role of the residues of the catalytic tetrad in the steroid double bond reduction mechanism. Biochemistry. 2008 Aug 12;47(32):8261-70. doi: 10.1021/bi800572s. Epub 2008 Jul 15. [Article]
  10. Faucher F, Cantin L, Luu-The V, Labrie F, Breton R: Crystal structures of human Delta4-3-ketosteroid 5beta-reductase (AKR1D1) reveal the presence of an alternative binding site responsible for substrate inhibition. Biochemistry. 2008 Dec 23;47(51):13537-46. doi: 10.1021/bi801276h. [Article]
  11. 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. [Article]
  12. Drury JE, Di Costanzo L, Penning TM, Christianson DW: Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and structure of the enzyme-inhibitor complex. J Biol Chem. 2009 Jul 24;284(30):19786-90. doi: 10.1074/jbc.C109.016931. Epub 2009 Jun 10. [Article]
  13. Di Costanzo L, Drury JE, Christianson DW, Penning TM: Structure and catalytic mechanism of human steroid 5beta-reductase (AKR1D1). Mol Cell Endocrinol. 2009 Mar 25;301(1-2):191-8. doi: 10.1016/j.mce.2008.09.013. Epub 2008 Sep 19. [Article]
  14. Chen M, Drury JE, Christianson DW, Penning TM: Conversion of human steroid 5beta-reductase (AKR1D1) into 3beta-hydroxysteroid dehydrogenase by single point mutation E120H: example of perfect enzyme engineering. J Biol Chem. 2012 May 11;287(20):16609-22. doi: 10.1074/jbc.M111.338780. Epub 2012 Mar 20. [Article]
  15. 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. [Article]
  16. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01216FinasterideapprovedunknowninhibitorDetails
DB074475beta-dihydrotestosteroneexperimentalunknownDetails
DB075573,20-PregnanedioneexperimentalunknownDetails
DB00548Azelaic acidapprovedyesinhibitorDetails
DB00717NorethisteroneapprovedunknownsubstrateDetails
DB00741Hydrocortisoneapproved, vet_approvedunknownsubstrateDetails
DB06077Lumateperoneapproved, investigationalnosubstrateDetails