Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

AKR1D1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

    Keywordsi

    Molecular functionOxidoreductase
    Biological processBile acid catabolism, Lipid degradation, Lipid metabolism, Steroid metabolism
    LigandNADP

    Enzyme and pathway databases

    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-RKiP51857

    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

    EuPathDBiHostDB:ENSG00000122787.14
    HGNCiHGNC:388 AKR1D1
    MIMi604741 gene
    neXtProtiNX_P51857

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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 dbSNP:rs121918343EnsemblClinVar.1
    Natural variantiVAR_044430133P → R in CBAS2. 1 PublicationCorresponds to variant dbSNP:rs267606649EnsemblClinVar.1
    Natural variantiVAR_033008198P → L in CBAS2. 1 PublicationCorresponds to variant dbSNP:rs121918342EnsemblClinVar.1
    Natural variantiVAR_044431261R → C in CBAS2. 1 PublicationCorresponds to variant dbSNP:rs267606650EnsemblClinVar.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

    DrugBankiDB07447 5-beta-DIHYDROTESTOSTERONE
    DB00548 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
    ProteomicsDBi56436
    56437 [P51857-2]
    56438 [P51857-3]

    PTM databases

    iPTMnetiP51857
    PhosphoSitePlusiP51857

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiENSG00000122787 Expressed in 51 organ(s), highest expression level in liver
    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

    3D structure databases

    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
    OMAiKIWTENL
    OrthoDBiEOG091G0D69
    PhylomeDBiP51857
    TreeFamiTF106492

    Family and domain databases

    CDDicd06660 Aldo_ket_red, 1 hit
    Gene3Di3.20.20.100, 1 hit
    InterProiView protein in InterPro
    IPR018170 Aldo/ket_reductase_CS
    IPR020471 Aldo/keto_reductase
    IPR023210 NADP_OxRdtase_dom
    IPR036812 NADP_OxRdtase_dom_sf
    PANTHERiPTHR11732 PTHR11732, 1 hit
    PfamiView protein in Pfam
    PF00248 Aldo_ket_red, 1 hit
    PIRSFiPIRSF000097 AKR, 1 hit
    PRINTSiPR00069 ALDKETRDTASE
    SUPFAMiSSF51430 SSF51430, 1 hit
    PROSITEiView protein in PROSITE
    PS00798 ALDOKETO_REDUCTASE_1, 1 hit
    PS00062 ALDOKETO_REDUCTASE_2, 1 hit
    PS00063 ALDOKETO_REDUCTASE_3, 1 hit

    Sequences (3+)i

    Sequence statusi: Complete.

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

    This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    C9J3U1C9J3U1_HUMAN
    3-oxo-5-beta-steroid 4-dehydrogenas...
    AKR1D1
    96Annotation score:

    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 dbSNP:rs121918343EnsemblClinVar.1
    Natural variantiVAR_044430133P → R in CBAS2. 1 PublicationCorresponds to variant dbSNP:rs267606649EnsemblClinVar.1
    Natural variantiVAR_033008198P → L in CBAS2. 1 PublicationCorresponds to variant dbSNP:rs121918342EnsemblClinVar.1
    Natural variantiVAR_044431261R → C in CBAS2. 1 PublicationCorresponds to variant dbSNP:rs267606650EnsemblClinVar.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

    Similar proteinsi

    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

    DrugBankiDB07447 5-beta-DIHYDROTESTOSTERONE
    DB00548 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
    ProteomicsDBi56436
    56437 [P51857-2]
    56438 [P51857-3]

    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
    EuPathDBiHostDB:ENSG00000122787.14
    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
    OMAiKIWTENL
    OrthoDBiEOG091G0D69
    PhylomeDBiP51857
    TreeFamiTF106492

    Enzyme and pathway databases

    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-RKiP51857

    Miscellaneous databases

    EvolutionaryTraceiP51857
    GenomeRNAii6718
    PROiPR:P51857
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000122787 Expressed in 51 organ(s), highest expression level in liver
    CleanExiHS_AKR1D1
    ExpressionAtlasiP51857 baseline and differential
    GenevisibleiP51857 HS

    Family and domain databases

    CDDicd06660 Aldo_ket_red, 1 hit
    Gene3Di3.20.20.100, 1 hit
    InterProiView protein in InterPro
    IPR018170 Aldo/ket_reductase_CS
    IPR020471 Aldo/keto_reductase
    IPR023210 NADP_OxRdtase_dom
    IPR036812 NADP_OxRdtase_dom_sf
    PANTHERiPTHR11732 PTHR11732, 1 hit
    PfamiView protein in Pfam
    PF00248 Aldo_ket_red, 1 hit
    PIRSFiPIRSF000097 AKR, 1 hit
    PRINTSiPR00069 ALDKETRDTASE
    SUPFAMiSSF51430 SSF51430, 1 hit
    PROSITEiView protein in PROSITE
    PS00798 ALDOKETO_REDUCTASE_1, 1 hit
    PS00062 ALDOKETO_REDUCTASE_2, 1 hit
    PS00063 ALDOKETO_REDUCTASE_3, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAK1D1_HUMAN
    AccessioniPrimary (citable) accession number: P51857
    Secondary accession number(s): A1L4P6
    , A8K060, B4DPN3, B4DPN8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: September 12, 2018
    This is version 154 of the entry and version 1 of the sequence. See 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families
    3. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    4. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again