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Identification
HMDB Protein ID HMDBP00074
Secondary Accession Numbers
  • 5303
  • HMDBP04885
Name Aldo-keto reductase family 1 member C4
Synonyms
  1. 3-alpha-HSD1
  2. 3-alpha-hydroxysteroid dehydrogenase type I
  3. CDR
  4. Chlordecone reductase
  5. DD-4
  6. DD4
  7. Dihydrodiol dehydrogenase 4
  8. HAKRA
Gene Name AKR1C4
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid dehydrogenase activity. The biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route.
Pathways
  • 11-beta-hydroxylase deficiency (CYP11B1)
  • 17-alpha-hydroxylase deficiency (CYP17)
  • 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
  • Androstenedione Metabolism
  • Apparent mineralocorticoid excess syndrome
  • 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)
  • Metabolism of xenobiotics by cytochrome P450
  • Primary bile acid biosynthesis
  • Steroid hormone biosynthesis
  • Steroidogenesis
  • Zellweger Syndrome
Reactions
Chlordecone alcohol + NADP → Chlordecone + NADPH details
A 3-alpha-hydroxysteroid + NAD(P)(+) → a 3-oxosteroid + NAD(P)H details
Androsterone + NAD → Androstanedione + NADH + Hydrogen Ion details
Androsterone + NADP → Androstanedione + NADPH + Hydrogen Ion details
Etiocholanolone + NAD → Etiocholanedione + NADH + Hydrogen Ion details
Etiocholanolone + NADP → Etiocholanedione + NADPH + Hydrogen Ion details
3a,7a-Dihydroxy-5b-cholestane + NAD → 7a-Hydroxy-5b-cholestan-3-one + NADH + Hydrogen Ion details
3a,7a-Dihydroxy-5b-cholestane + NADP → 7a-Hydroxy-5b-cholestan-3-one + NADPH + Hydrogen Ion details
5-b-Cholestane-3a ,7a ,12a-triol + NAD → 7a,12a-Dihydroxy-5b-cholestan-3-one + NADH + Hydrogen Ion details
5-b-Cholestane-3a ,7a ,12a-triol + NADP → 7a,12a-Dihydroxy-5b-cholestan-3-one + NADPH + Hydrogen Ion details
Tetrahydrocortisone + NAD → 17a,21-Dihydroxy-5b-pregnane-3,11,20-trione + NADH + Hydrogen Ion details
17a,21-Dihydroxy-5b-pregnane-3,11,20-trione + Hydrogen Ion + NADPH → Tetrahydrocortisone + NADP details
Tetrahydrocortisol + NAD → Dihydrocortisol + NADH + Hydrogen Ion details
Tetrahydrocortisol + NADP → Dihydrocortisol + NADPH + Hydrogen Ion details
3a,11b,21-Trihydroxy-20-oxo-5b-pregnan-18-al + NAD → 11b,21-Dihydroxy-3,20-oxo-5b-pregnan-18-al + NADH + Hydrogen Ion details
3a,11b,21-Trihydroxy-20-oxo-5b-pregnan-18-al + NADP → 11b,21-Dihydroxy-3,20-oxo-5b-pregnan-18-al + NADPH + Hydrogen Ion details
Tetrahydrocorticosterone + NAD → 11b,21-Dihydroxy-5b-pregnane-3,20-dione + NADH + Hydrogen Ion details
Tetrahydrocorticosterone + NADP → 11b,21-Dihydroxy-5b-pregnane-3,20-dione + NADPH + Hydrogen Ion details
3a,21-Dihydroxy-5b-pregnane-11,20-dione + NAD → 21-Hydroxy-5b-pregnane-3,11,20-trione + NADH + Hydrogen Ion details
3a,21-Dihydroxy-5b-pregnane-11,20-dione + NADP → 21-Hydroxy-5b-pregnane-3,11,20-trione + NADPH + Hydrogen Ion details
3a-Hydroxy-5b-pregnane-20-one + NAD → 5a-Pregnane-3,20-dione + NADH + Hydrogen Ion details
3a-Hydroxy-5b-pregnane-20-one + NADP → 5a-Pregnane-3,20-dione + NADPH + Hydrogen Ion details
Dihydrotestosterone + NADPH + Hydrogen Ion → Androstan-3alpha,17beta-diol + NADP details
GO Classification
Biological Process
bile acid biosynthetic process
daunorubicin metabolic process
doxorubicin metabolic process
cellular response to jasmonic acid stimulus
androgen metabolic process
Cellular Component
cytosol
Function
catalytic activity
oxidoreductase activity
Molecular Function
electron carrier activity
aldo-keto reductase (NADP) activity
retinal dehydrogenase activity
androsterone dehydrogenase (B-specific) activity
oxidoreductase activity, acting on NADH or NADPH, quinone or similar compound as acceptor
androsterone dehydrogenase activity
bile acid transmembrane transporter activity
chlordecone reductase activity
Process
metabolic process
oxidation reduction
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 10
Locus 10p15.1
SNPs AKR1C4
Gene Sequence
>972 bp
ATGGATCCCAAATATCAGCGTGTAGAGCTAAATGATGGTCACTTCATGCCCGTATTGGGA
TTTGGCACCTATGCACCTCCAGAGGTTCCGAGGAACAGAGCTGTAGAGGTCACCAAATTA
GCAATAGAAGCTGGCTTCCGCCATATTGATTCTGCTTATTTATACAATAATGAGGAGCAG
GTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTC
TACACTTCAAAGCTTTGGTGCACTTTCTTTCAACCACAGATGGTCCAACCAGCCTTGGAA
AGCTCACTGAAAAAACTTCAACTGGACTATGTTGACCTCTATCTTCTTCATTTCCCAATG
GCTCTCAAGCCAGGTGAGACGCCACTACCAAAAGATGAAAATGGAAAAGTAATATTCGAC
ACAGTGGATCTCTCTGCCACATGGGAGGTCATGGAGAAGTGTAAGGATGCAGGATTGGCC
AAGTCCATCGGGGTGTCAAACTTCAACTGCAGGCAGCTGGAGATGATCCTCAACAAGCCA
GGACTCAAGTACAAGCCTGTCTGCAACCAGGTAGAATGTCATCCTTACCTCAACCAGAGC
AAACTGCTGGATTTCTGCAAGTCAAAAGACATTGTTCTGGTTGCCCACAGTGCTCTGGGA
ACCCAACGACATAAACTATGGGTGGACCCAAACTCCCCAGTTCTTTTGGAGGACCCAGTT
CTTTGTGCCTTAGCAAAGAAACACAAACGAACCCCAGCCCTGATTGCCCTGCGCTACCAG
CTGCAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGGATCAGAGAGAAC
ATCCAGGTTTTTGAATTCCAGTTGACATCAGAGGATATGAAAGTTCTAGATGGTCTAAAC
AGAAATTATCGATATGTTGTCATGGATTTTCTTATGGACCATCCTGATTATCCATTTTCA
GATGAATATTAG
Protein Properties
Number of Residues 323
Molecular Weight 37094.57
Theoretical pI 7.164
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Aldo-keto reductase family 1 member C4
MDPKYQRVELNDGHFMPVLGFGTYAPPEVPRNRAVEVTKLAIEAGFRHIDSAYLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWCTFFQPQMVQPALESSLKKLQLDYVDLYLLHFPM
ALKPGETPLPKDENGKVIFDTVDLSATWEVMEKCKDAGLAKSIGVSNFNCRQLEMILNKP
GLKYKPVCNQVECHPYLNQSKLLDFCKSKDIVLVAHSALGTQRHKLWVDPNSPVLLEDPV
LCALAKKHKQTPALIALRYQLQRGVVVLAKSYNEQRIRENIQVFEFQLTSEDMKVLDGLN
RNYRYVVMDFLMDHPDYPFSDEY
GenBank ID Protein 7328948
UniProtKB/Swiss-Prot ID P17516
UniProtKB/Swiss-Prot Entry Name AK1C4_HUMAN
PDB IDs
GenBank Gene ID AB031085
GeneCard ID AKR1C4
GenAtlas ID AKR1C4
HGNC ID HGNC:387
References
General References
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