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Protein

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

Gene

AKR1D1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

5-beta-cholestan-3-one + NADP+ = cholest-4-en-3-one + NADPH.1 Publication
17,21-dihydroxy-5-beta-pregnane-3,11,20-trione + NADP+ = cortisone + NADPH.1 Publication

Enzyme regulationi

Subject to inhibition by high substrate concentrations. Inhibited by testosterone concentrations above 10 µM.1 Publication

Kineticsi

  1. KM=2.7 µM for testosterone1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei26Substrate1
    Binding sitei53NADP5 Publications1
    Active sitei58Proton donor1
    Binding sitei58Substrate1
    Binding sitei89Substrate1
    Binding sitei120Substrate1
    Binding sitei132Substrate1
    Binding sitei193NADP5 Publications1
    Binding sitei230Substrate1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi22 – 26NADP5 Publications5
    Nucleotide bindingi169 – 170NADP5 Publications2
    Nucleotide bindingi219 – 224NADP5 Publications6
    Nucleotide bindingi273 – 283NADP5 PublicationsAdd BLAST11

    GO - Molecular functioni

    • aldo-keto reductase (NADP) activity Source: Reactome
    • delta4-3-oxosteroid 5beta-reductase activity Source: UniProtKB-EC
    • steroid binding Source: UniProtKB

    GO - Biological processi

    • androgen metabolic process Source: UniProtKB
    • bile acid biosynthetic process Source: UniProtKB
    • bile acid catabolic process Source: UniProtKB-KW
    • C21-steroid hormone metabolic process Source: UniProtKB
    • cholesterol catabolic process Source: UniProtKB
    • digestion Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Bile acid catabolism, Lipid degradation, Lipid metabolism, Steroid metabolism

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    BioCyciZFISH:HS04603-MONOMER.
    BRENDAi1.3.1.3. 2681.
    ReactomeiR-HSA-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
    R-HSA-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
    R-HSA-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
    SABIO-RKP51857.

    Chemistry databases

    SwissLipidsiSLP:000001272. [P51857-1]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    3-oxo-5-beta-steroid 4-dehydrogenase (EC:1.3.1.31 Publication)
    Alternative name(s):
    Aldo-keto reductase family 1 member D1
    Delta(4)-3-ketosteroid 5-beta-reductase
    Delta(4)-3-oxosteroid 5-beta-reductase
    Gene namesi
    Name:AKR1D1
    Synonyms:SRD5B1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:388. AKR1D1.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Congenital bile acid synthesis defect 2 (CBAS2)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA condition characterized by jaundice, intrahepatic cholestasis and hepatic failure. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.
    See also OMIM:235555
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_033007106L → F in CBAS2. 1 PublicationCorresponds to variant rs121918343dbSNPEnsembl.1
    Natural variantiVAR_044430133P → R in CBAS2. 1 PublicationCorresponds to variant rs267606649dbSNPEnsembl.1
    Natural variantiVAR_033008198P → L in CBAS2. 1 PublicationCorresponds to variant rs121918342dbSNPEnsembl.1
    Natural variantiVAR_044431261R → C in CBAS2. 1 PublicationCorresponds to variant rs267606650dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi58Y → A: Loss of activity. 1 Publication1
    Mutagenesisi120E → A: Loss of activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Intrahepatic cholestasis

    Organism-specific databases

    DisGeNETi6718.
    MalaCardsiAKR1D1.
    MIMi235555. phenotype.
    OpenTargetsiENSG00000122787.
    Orphaneti79303. Congenital bile acid synthesis defect type 2.
    PharmGKBiPA24681.

    Chemistry databases

    DrugBankiDB00548. Azelaic Acid.
    DB01216. Finasteride.

    Polymorphism and mutation databases

    BioMutaiAKR1D1.
    DMDMi1703007.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001246691 – 3263-oxo-5-beta-steroid 4-dehydrogenaseAdd BLAST326

    Proteomic databases

    EPDiP51857.
    MaxQBiP51857.
    PaxDbiP51857.
    PeptideAtlasiP51857.
    PRIDEiP51857.

    PTM databases

    iPTMnetiP51857.
    PhosphoSitePlusiP51857.

    Expressioni

    Tissue specificityi

    Highly expressed in liver. Expressed in testis and weakly in colon.1 Publication

    Gene expression databases

    BgeeiENSG00000122787.
    CleanExiHS_AKR1D1.
    ExpressionAtlasiP51857. baseline and differential.
    GenevisibleiP51857. HS.

    Organism-specific databases

    HPAiHPA057002.

    Interactioni

    Protein-protein interaction databases

    BioGridi112596. 8 interactors.
    STRINGi9606.ENSP00000242375.

    Structurei

    Secondary structure

    1326
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi9 – 11Combined sources3
    Beta strandi17 – 21Combined sources5
    Turni29 – 31Combined sources3
    Helixi36 – 47Combined sources12
    Beta strandi51 – 53Combined sources3
    Helixi56 – 58Combined sources3
    Helixi61 – 73Combined sources13
    Helixi79 – 81Combined sources3
    Beta strandi83 – 88Combined sources6
    Helixi90 – 92Combined sources3
    Helixi95 – 97Combined sources3
    Helixi98 – 109Combined sources12
    Beta strandi114 – 120Combined sources7
    Helixi147 – 159Combined sources13
    Beta strandi162 – 170Combined sources9
    Helixi173 – 180Combined sources8
    Beta strandi191 – 195Combined sources5
    Helixi203 – 211Combined sources9
    Beta strandi215 – 220Combined sources6
    Turni228 – 230Combined sources3
    Helixi238 – 240Combined sources3
    Helixi242 – 250Combined sources9
    Helixi255 – 265Combined sources11
    Helixi277 – 284Combined sources8
    Helixi293 – 300Combined sources8
    Helixi312 – 314Combined sources3
    Beta strandi321 – 324Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3BURX-ray1.62A/B1-326[»]
    3BUVX-ray1.35A/B1-326[»]
    3BV7X-ray1.79A/B1-326[»]
    3CAQX-ray2.20A/B1-326[»]
    3CASX-ray2.00A/B1-326[»]
    3CAVX-ray1.90A/B1-326[»]
    3CMFX-ray1.90A/B1-326[»]
    3COTX-ray2.03A/B1-326[»]
    3DOPX-ray2.00A/B1-326[»]
    3G1RX-ray1.70A/B1-326[»]
    3UZWX-ray1.89A/B1-326[»]
    3UZXX-ray1.64A/B1-326[»]
    3UZYX-ray1.83A/B1-326[»]
    3UZZX-ray1.82A/B1-326[»]
    ProteinModelPortaliP51857.
    SMRiP51857.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP51857.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldo/keto reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1577. Eukaryota.
    COG0656. LUCA.
    GeneTreeiENSGT00760000119041.
    HOGENOMiHOG000250272.
    HOVERGENiHBG000020.
    InParanoidiP51857.
    KOiK00251.
    OMAiQLLMWRD.
    OrthoDBiEOG091G0D69.
    PhylomeDBiP51857.
    TreeFamiTF106492.

    Family and domain databases

    CDDicd06660. Aldo_ket_red. 1 hit.
    Gene3Di3.20.20.100. 1 hit.
    InterProiIPR001395. Aldo/ket_red/Kv-b.
    IPR018170. Aldo/ket_reductase_CS.
    IPR020471. Aldo/keto_reductase.
    IPR023210. NADP_OxRdtase_dom.
    [Graphical view]
    PANTHERiPTHR11732. PTHR11732. 2 hits.
    PfamiPF00248. Aldo_ket_red. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000097. AKR. 1 hit.
    PRINTSiPR00069. ALDKETRDTASE.
    SUPFAMiSSF51430. SSF51430. 1 hit.
    PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
    PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
    PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P51857-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MDLSAASHRI PLSDGNSIPI IGLGTYSEPK STPKGACATS VKVAIDTGYR
    60 70 80 90 100
    HIDGAYIYQN EHEVGEAIRE KIAEGKVRRE DIFYCGKLWA TNHVPEMVRP
    110 120 130 140 150
    TLERTLRVLQ LDYVDLYIIE VPMAFKPGDE IYPRDENGKW LYHKSNLCAT
    160 170 180 190 200
    WEAMEACKDA GLVKSLGVSN FNRRQLELIL NKPGLKHKPV SNQVECHPYF
    210 220 230 240 250
    TQPKLLKFCQ QHDIVITAYS PLGTSRNPIW VNVSSPPLLK DALLNSLGKR
    260 270 280 290 300
    YNKTAAQIVL RFNIQRGVVV IPKSFNLERI KENFQIFDFS LTEEEMKDIE
    310 320
    ALNKNVRFVE LLMWRDHPEY PFHDEY
    Length:326
    Mass (Da):37,377
    Last modified:October 1, 1996 - v1
    Checksum:i1FE02B95398A0A6F
    GO
    Isoform 2 (identifier: P51857-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         286-326: IFDFSLTEEEMKDIEALNKNVRFVELLMWRDHPEYPFHDEY → VARSS

    Note: No experimental confirmation available.
    Show »
    Length:290
    Mass (Da):32,748
    Checksum:iF2C7686DA906C0EC
    GO
    Isoform 3 (identifier: P51857-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         153-193: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:285
    Mass (Da):32,890
    Checksum:i5017C36EB0EB13D9
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti14D → V in BAF82114 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_033007106L → F in CBAS2. 1 PublicationCorresponds to variant rs121918343dbSNPEnsembl.1
    Natural variantiVAR_044430133P → R in CBAS2. 1 PublicationCorresponds to variant rs267606649dbSNPEnsembl.1
    Natural variantiVAR_033008198P → L in CBAS2. 1 PublicationCorresponds to variant rs121918342dbSNPEnsembl.1
    Natural variantiVAR_044431261R → C in CBAS2. 1 PublicationCorresponds to variant rs267606650dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_042913153 – 193Missing in isoform 3. 1 PublicationAdd BLAST41
    Alternative sequenceiVSP_042901286 – 326IFDFS…FHDEY → VARSS in isoform 2. 1 PublicationAdd BLAST41

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z28339 mRNA. Translation: CAA82193.1.
    AF283659
    , AF283651, AF283652, AF283653, AF283654, AF283655, AF283656, AF283657, AF283658 Genomic DNA. Translation: AAG39381.1.
    AK289425 mRNA. Translation: BAF82114.1.
    AK298421 mRNA. Translation: BAG60645.1.
    AK298428 mRNA. Translation: BAG60650.1.
    AC009263 Genomic DNA. No translation available.
    AC024082 Genomic DNA. No translation available.
    AC083867 Genomic DNA. No translation available.
    CH236950 Genomic DNA. Translation: EAL24049.1.
    CH471070 Genomic DNA. Translation: EAW83881.1.
    BC130625 mRNA. Translation: AAI30626.1.
    BC130627 mRNA. Translation: AAI30628.1.
    CCDSiCCDS55169.1. [P51857-2]
    CCDS55170.1. [P51857-3]
    CCDS5846.1. [P51857-1]
    PIRiS41120.
    RefSeqiNP_001177835.1. NM_001190906.1. [P51857-3]
    NP_001177836.1. NM_001190907.1. [P51857-2]
    NP_005980.1. NM_005989.3. [P51857-1]
    UniGeneiHs.201667.
    Hs.740214.

    Genome annotation databases

    EnsembliENST00000242375; ENSP00000242375; ENSG00000122787. [P51857-1]
    ENST00000411726; ENSP00000402374; ENSG00000122787. [P51857-3]
    ENST00000432161; ENSP00000389197; ENSG00000122787. [P51857-2]
    GeneIDi6718.
    KEGGihsa:6718.
    UCSCiuc003vtz.4. human. [P51857-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z28339 mRNA. Translation: CAA82193.1.
    AF283659
    , AF283651, AF283652, AF283653, AF283654, AF283655, AF283656, AF283657, AF283658 Genomic DNA. Translation: AAG39381.1.
    AK289425 mRNA. Translation: BAF82114.1.
    AK298421 mRNA. Translation: BAG60645.1.
    AK298428 mRNA. Translation: BAG60650.1.
    AC009263 Genomic DNA. No translation available.
    AC024082 Genomic DNA. No translation available.
    AC083867 Genomic DNA. No translation available.
    CH236950 Genomic DNA. Translation: EAL24049.1.
    CH471070 Genomic DNA. Translation: EAW83881.1.
    BC130625 mRNA. Translation: AAI30626.1.
    BC130627 mRNA. Translation: AAI30628.1.
    CCDSiCCDS55169.1. [P51857-2]
    CCDS55170.1. [P51857-3]
    CCDS5846.1. [P51857-1]
    PIRiS41120.
    RefSeqiNP_001177835.1. NM_001190906.1. [P51857-3]
    NP_001177836.1. NM_001190907.1. [P51857-2]
    NP_005980.1. NM_005989.3. [P51857-1]
    UniGeneiHs.201667.
    Hs.740214.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3BURX-ray1.62A/B1-326[»]
    3BUVX-ray1.35A/B1-326[»]
    3BV7X-ray1.79A/B1-326[»]
    3CAQX-ray2.20A/B1-326[»]
    3CASX-ray2.00A/B1-326[»]
    3CAVX-ray1.90A/B1-326[»]
    3CMFX-ray1.90A/B1-326[»]
    3COTX-ray2.03A/B1-326[»]
    3DOPX-ray2.00A/B1-326[»]
    3G1RX-ray1.70A/B1-326[»]
    3UZWX-ray1.89A/B1-326[»]
    3UZXX-ray1.64A/B1-326[»]
    3UZYX-ray1.83A/B1-326[»]
    3UZZX-ray1.82A/B1-326[»]
    ProteinModelPortaliP51857.
    SMRiP51857.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi112596. 8 interactors.
    STRINGi9606.ENSP00000242375.

    Chemistry databases

    DrugBankiDB00548. Azelaic Acid.
    DB01216. Finasteride.
    SwissLipidsiSLP:000001272. [P51857-1]

    PTM databases

    iPTMnetiP51857.
    PhosphoSitePlusiP51857.

    Polymorphism and mutation databases

    BioMutaiAKR1D1.
    DMDMi1703007.

    Proteomic databases

    EPDiP51857.
    MaxQBiP51857.
    PaxDbiP51857.
    PeptideAtlasiP51857.
    PRIDEiP51857.

    Protocols and materials databases

    DNASUi6718.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000242375; ENSP00000242375; ENSG00000122787. [P51857-1]
    ENST00000411726; ENSP00000402374; ENSG00000122787. [P51857-3]
    ENST00000432161; ENSP00000389197; ENSG00000122787. [P51857-2]
    GeneIDi6718.
    KEGGihsa:6718.
    UCSCiuc003vtz.4. human. [P51857-1]

    Organism-specific databases

    CTDi6718.
    DisGeNETi6718.
    GeneCardsiAKR1D1.
    HGNCiHGNC:388. AKR1D1.
    HPAiHPA057002.
    MalaCardsiAKR1D1.
    MIMi235555. phenotype.
    604741. gene.
    neXtProtiNX_P51857.
    OpenTargetsiENSG00000122787.
    Orphaneti79303. Congenital bile acid synthesis defect type 2.
    PharmGKBiPA24681.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1577. Eukaryota.
    COG0656. LUCA.
    GeneTreeiENSGT00760000119041.
    HOGENOMiHOG000250272.
    HOVERGENiHBG000020.
    InParanoidiP51857.
    KOiK00251.
    OMAiQLLMWRD.
    OrthoDBiEOG091G0D69.
    PhylomeDBiP51857.
    TreeFamiTF106492.

    Enzyme and pathway databases

    BioCyciZFISH:HS04603-MONOMER.
    BRENDAi1.3.1.3. 2681.
    ReactomeiR-HSA-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
    R-HSA-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
    R-HSA-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
    SABIO-RKP51857.

    Miscellaneous databases

    EvolutionaryTraceiP51857.
    GenomeRNAii6718.
    PROiP51857.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000122787.
    CleanExiHS_AKR1D1.
    ExpressionAtlasiP51857. baseline and differential.
    GenevisibleiP51857. HS.

    Family and domain databases

    CDDicd06660. Aldo_ket_red. 1 hit.
    Gene3Di3.20.20.100. 1 hit.
    InterProiIPR001395. Aldo/ket_red/Kv-b.
    IPR018170. Aldo/ket_reductase_CS.
    IPR020471. Aldo/keto_reductase.
    IPR023210. NADP_OxRdtase_dom.
    [Graphical view]
    PANTHERiPTHR11732. PTHR11732. 2 hits.
    PfamiPF00248. Aldo_ket_red. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000097. AKR. 1 hit.
    PRINTSiPR00069. ALDKETRDTASE.
    SUPFAMiSSF51430. SSF51430. 1 hit.
    PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
    PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
    PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAK1D1_HUMAN
    AccessioniPrimary (citable) accession number: P51857
    Secondary accession number(s): A1L4P6
    , A8K060, B4DPN3, B4DPN8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: November 2, 2016
    This is version 145 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.