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Protein

Aldo-keto reductase family 1 member C1

Gene

AKR1C1

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

Functioni

Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.2 Publications

Catalytic activityi

17-alpha,20-alpha-dihydroxypregn-4-en-3-one + NAD(P)+ = 17-alpha-hydroxyprogesterone + NAD(P)H.2 Publications
Trans-1,2-dihydrobenzene-1,2-diol + NADP+ = catechol + NADPH.2 Publications
Indan-1-ol + NAD(P)+ = indanone + NAD(P)H.1 Publication

Activity regulationi

Inhibited by hexestrol with an IC50 of 9.5 µM, 1,10-phenanthroline with an IC50 of 55 µM, 1,7-phenanthroline with an IC50 of 72 µM, flufenamic acid with an IC50 of 6.0 µM, indomethacin with an IC50 of 140 µM, ibuprofen with an IC50 of 950 µM, lithocholic acid with an IC50 of 25 µM, ursodeoxycholic acid with an IC50 of 340 µM and chenodeoxycholic acid with an IC50 of 570 µM.1 Publication

Kineticsi

  1. KM=5 µM for (s)-tetralol2 Publications
  2. KM=38 µM for (s)-indan-1-ol2 Publications
  3. KM=580 µM for benzene dihydrodiol2 Publications
  4. KM=3 µM for 5-beta-pregnane-3-alpha,20-alpha-diol2 Publications
  5. KM=3 µM for 5-beta-pregnan-20-alpha-ol-3-one2 Publications
  6. KM=12 µM for 4-pregnen-20-alpha-ol-3-one2 Publications
  7. KM=133 µM for 9-alpha,11-beta-prostaglandin F22 Publications
  8. KM=2 µM for 5-beta-pregnan-3-alpha-ol-20-one2 Publications
  9. KM=1 µM for 5-beta-androstane-3,17-dione2 Publications
  10. KM=12 µM for prostaglandin D22 Publications
  11. KM=0.6 µM for 20-alpha-hydroxyprogesterone (with NADH)2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei24Substrate1
    Binding sitei50NADP2 Publications1
    Sitei54Important for substrate specificityBy similarity1
    Active sitei55Proton donorBy similarity1
    Sitei84Lowers pKa of active site TyrBy similarity1
    Binding sitei117SubstrateBy similarity1
    Binding sitei190NADP2 Publications1
    Binding sitei222Substrate1
    Sitei222May be involved in the mediating step between the transformation of progesterone and the release of the cofactor1
    Binding sitei227Substrate1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi20 – 24NADP2 Publications5
    Nucleotide bindingi166 – 167NADP2 Publications2
    Nucleotide bindingi216 – 222NADP2 Publications7
    Nucleotide bindingi270 – 280NADP2 PublicationsAdd BLAST11

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    LigandNADP

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10741-MONOMER
    BRENDAi1.1.1.149 2681
    1.1.1.270 2681
    1.1.1.50 2681
    1.3.1.20 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
    R-HSA-975634 Retinoid metabolism and transport
    SABIO-RKiQ04828
    SIGNORiQ04828

    Chemistry databases

    SwissLipidsiSLP:000000802

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aldo-keto reductase family 1 member C1 (EC:1.1.1.-)
    Alternative name(s):
    20-alpha-hydroxysteroid dehydrogenase (EC:1.1.1.1492 Publications)
    Short name:
    20-alpha-HSD
    Chlordecone reductase homolog HAKRC
    Dihydrodiol dehydrogenase 1/2
    Short name:
    DD1/DD2
    High-affinity hepatic bile acid-binding protein
    Short name:
    HBAB
    Indanol dehydrogenase (EC:1.1.1.1121 Publication)
    Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase (EC:1.3.1.202 Publications)
    Gene namesi
    Name:AKR1C1
    Synonyms:DDH, DDH1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000187134.12
    HGNCiHGNC:384 AKR1C1
    MIMi600449 gene
    neXtProtiNX_Q04828

    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

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi127E → D: 30-fold decrease in k(cat)/K(m) value for progesterone reduction; no effect on the K(m) value. 1 Publication1
    Mutagenesisi222H → I: Marked decrease in k(cat)/K(m) value for progesterone; 24-fold decrease for progesterone reduction; 18-fold decrease for 20alpha-OHProg oxidation. 95-fold decrease in K(m) value for NADPH. 1 Publication1
    Mutagenesisi222H → S: Marked decrease in k(cat)/K(m) value for progesterone; 10-fold decrease for progesterone reduction; 3-fold decrease for 20alpha-OHProg oxidation. 10-fold decrease in K(m) value for NADPH. 1 Publication1
    Mutagenesisi304R → L: 70-fold decrease in progesterone reduction. No effect on DHT reduction. 1 Publication1
    Mutagenesisi305Y → F: No effect on progesterone reduction. 1 Publication1
    Mutagenesisi307T → V: No effect on progesterone reduction. 1 Publication1
    Mutagenesisi309D → V: No effect on progesterone reduction. 1 Publication1

    Organism-specific databases

    DisGeNETi1645
    MalaCardsiAKR1C1
    OpenTargetsiENSG00000187134
    PharmGKBiPA24677

    Chemistry databases

    ChEMBLiCHEMBL5905
    DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
    DB00945 Acetylsalicylic acid
    DB07931 Hexestrol
    DB00157 NADH
    DB00936 Salicylic acid

    Polymorphism and mutation databases

    BioMutaiAKR1C1
    DMDMi416877

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001246331 – 323Aldo-keto reductase family 1 member C1Add BLAST323

    Proteomic databases

    EPDiQ04828
    MaxQBiQ04828
    PaxDbiQ04828
    PeptideAtlasiQ04828
    PRIDEiQ04828
    ProteomicsDBi58285

    PTM databases

    iPTMnetiQ04828
    PhosphoSitePlusiQ04828
    SwissPalmiQ04828

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested including liver, prostate, testis, adrenal gland, brain, uterus, mammary gland and keratinocytes. Highest levels found in liver, mammary gland and brain.1 Publication

    Gene expression databases

    BgeeiENSG00000187134 Expressed in 102 organ(s), highest expression level in right lobe of liver
    CleanExiHS_AKR1C1
    ExpressionAtlasiQ04828 baseline and differential
    GenevisibleiQ04828 HS

    Organism-specific databases

    HPAiCAB047303
    HPA068265

    Interactioni

    Subunit structurei

    Monomer.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PTPN3P260455EBI-2116455,EBI-1047946

    Protein-protein interaction databases

    BioGridi108012, 8 interactors
    IntActiQ04828, 4 interactors
    MINTiQ04828
    STRINGi9606.ENSP00000370254

    Chemistry databases

    BindingDBiQ04828

    Structurei

    Secondary structure

    1323
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ04828
    SMRiQ04828
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ04828

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldo/keto reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1577 Eukaryota
    COG0656 LUCA
    GeneTreeiENSGT00760000119041
    HOGENOMiHOG000250272
    HOVERGENiHBG000020
    InParanoidiQ04828
    KOiK00212
    OMAiINQGRRY
    PhylomeDBiQ04828
    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

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

    Q04828-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MDSKYQCVKL NDGHFMPVLG FGTYAPAEVP KSKALEATKL AIEAGFRHID
    60 70 80 90 100
    SAHLYNNEEQ VGLAIRSKIA DGSVKREDIF YTSKLWCNSH RPELVRPALE
    110 120 130 140 150
    RSLKNLQLDY VDLYLIHFPV SVKPGEEVIP KDENGKILFD TVDLCATWEA
    160 170 180 190 200
    VEKCKDAGLA KSIGVSNFNR RQLEMILNKP GLKYKPVCNQ VECHPYFNQR
    210 220 230 240 250
    KLLDFCKSKD IVLVAYSALG SHREEPWVDP NSPVLLEDPV LCALAKKHKR
    260 270 280 290 300
    TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTS EEMKAIDGLN
    310 320
    RNVRYLTLDI FAGPPNYPFS DEY
    Length:323
    Mass (Da):36,788
    Last modified:October 1, 1993 - v1
    Checksum:i9CB215478FBD29D5
    GO

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H0Y804H0Y804_HUMAN
    Aldo-keto reductase family 1 member...
    AKR1C1
    248Annotation score:
    A6NHU4A6NHU4_HUMAN
    Aldo-keto reductase family 1 member...
    AKR1C1
    205Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti3S → A no nucleotide entry (PubMed:7626489).Curated1
    Sequence conflicti95V → D no nucleotide entry (PubMed:7626489).Curated1
    Sequence conflicti95V → D in AAD14012 (PubMed:8274401).Curated1
    Sequence conflicti158G → E no nucleotide entry (PubMed:7626489).Curated1
    Sequence conflicti158G → E in AAD14012 (PubMed:8274401).Curated1
    Sequence conflicti171 – 172RQ → ST no nucleotide entry (PubMed:7626489).Curated2
    Sequence conflicti171 – 172RQ → ST in AAD14012 (PubMed:8274401).Curated2
    Sequence conflicti183 – 184KY → QV no nucleotide entry (PubMed:7626489).Curated2
    Sequence conflicti183 – 184KY → QV in AAD14012 (PubMed:8274401).Curated2
    Sequence conflicti222H → L no nucleotide entry (PubMed:7626489).Curated1
    Sequence conflicti222H → L in AAD14012 (PubMed:8274401).Curated1
    Sequence conflicti319F → I no nucleotide entry (PubMed:7626489).Curated1
    Sequence conflicti319F → I in AAD14012 (PubMed:8274401).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_048214170R → H. Corresponds to variant dbSNP:rs139588200Ensembl.1
    Natural variantiVAR_048215172Q → L. Corresponds to variant dbSNP:rs11474Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M86609 mRNA Translation: AAB02880.1
    U05861
    , U05853, U05854, U05855, U05857, U05858, U05859, U05860 Genomic DNA Translation: AAA18115.1
    U05684 mRNA Translation: AAA16227.1
    AB031083 mRNA Translation: BAA92883.1
    AB032150 Genomic DNA Translation: BAA92886.1
    BT007197 mRNA Translation: AAP35861.1
    AC091817 Genomic DNA No translation available.
    AL713867 Genomic DNA No translation available.
    BC015490 mRNA Translation: AAH15490.1
    BC020216 mRNA Translation: AAH20216.1
    BC040210 mRNA Translation: AAH40210.1
    S68290 mRNA Translation: AAD14012.1
    D26124 mRNA Translation: BAA05121.1
    CCDSiCCDS7061.1
    PIRiA53436
    I73675
    S59619
    S61515
    RefSeqiNP_001344.2, NM_001353.5
    UniGeneiHs.460260

    Genome annotation databases

    EnsembliENST00000380872; ENSP00000370254; ENSG00000187134
    GeneIDi1645
    KEGGihsa:1645
    UCSCiuc001ihq.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M86609 mRNA Translation: AAB02880.1
    U05861
    , U05853, U05854, U05855, U05857, U05858, U05859, U05860 Genomic DNA Translation: AAA18115.1
    U05684 mRNA Translation: AAA16227.1
    AB031083 mRNA Translation: BAA92883.1
    AB032150 Genomic DNA Translation: BAA92886.1
    BT007197 mRNA Translation: AAP35861.1
    AC091817 Genomic DNA No translation available.
    AL713867 Genomic DNA No translation available.
    BC015490 mRNA Translation: AAH15490.1
    BC020216 mRNA Translation: AAH20216.1
    BC040210 mRNA Translation: AAH40210.1
    S68290 mRNA Translation: AAD14012.1
    D26124 mRNA Translation: BAA05121.1
    CCDSiCCDS7061.1
    PIRiA53436
    I73675
    S59619
    S61515
    RefSeqiNP_001344.2, NM_001353.5
    UniGeneiHs.460260

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1MRQX-ray1.59A2-323[»]
    3C3UX-ray1.80A1-323[»]
    3GUGX-ray1.90A1-323[»]
    3NTYX-ray1.87A1-323[»]
    4YVPX-ray2.60A/B1-323[»]
    ProteinModelPortaliQ04828
    SMRiQ04828
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108012, 8 interactors
    IntActiQ04828, 4 interactors
    MINTiQ04828
    STRINGi9606.ENSP00000370254

    Chemistry databases

    BindingDBiQ04828
    ChEMBLiCHEMBL5905
    DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
    DB00945 Acetylsalicylic acid
    DB07931 Hexestrol
    DB00157 NADH
    DB00936 Salicylic acid
    SwissLipidsiSLP:000000802

    PTM databases

    iPTMnetiQ04828
    PhosphoSitePlusiQ04828
    SwissPalmiQ04828

    Polymorphism and mutation databases

    BioMutaiAKR1C1
    DMDMi416877

    Proteomic databases

    EPDiQ04828
    MaxQBiQ04828
    PaxDbiQ04828
    PeptideAtlasiQ04828
    PRIDEiQ04828
    ProteomicsDBi58285

    Protocols and materials databases

    DNASUi1645
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000380872; ENSP00000370254; ENSG00000187134
    GeneIDi1645
    KEGGihsa:1645
    UCSCiuc001ihq.4 human

    Organism-specific databases

    CTDi1645
    DisGeNETi1645
    EuPathDBiHostDB:ENSG00000187134.12
    GeneCardsiAKR1C1
    HGNCiHGNC:384 AKR1C1
    HPAiCAB047303
    HPA068265
    MalaCardsiAKR1C1
    MIMi600449 gene
    neXtProtiNX_Q04828
    OpenTargetsiENSG00000187134
    PharmGKBiPA24677
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1577 Eukaryota
    COG0656 LUCA
    GeneTreeiENSGT00760000119041
    HOGENOMiHOG000250272
    HOVERGENiHBG000020
    InParanoidiQ04828
    KOiK00212
    OMAiINQGRRY
    PhylomeDBiQ04828
    TreeFamiTF106492

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10741-MONOMER
    BRENDAi1.1.1.149 2681
    1.1.1.270 2681
    1.1.1.50 2681
    1.3.1.20 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
    R-HSA-975634 Retinoid metabolism and transport
    SABIO-RKiQ04828
    SIGNORiQ04828

    Miscellaneous databases

    ChiTaRSiAKR1C1 human
    EvolutionaryTraceiQ04828
    GeneWikiiAKR1C1
    GenomeRNAii1645
    PROiPR:Q04828
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000187134 Expressed in 102 organ(s), highest expression level in right lobe of liver
    CleanExiHS_AKR1C1
    ExpressionAtlasiQ04828 baseline and differential
    GenevisibleiQ04828 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 nameiAK1C1_HUMAN
    AccessioniPrimary (citable) accession number: Q04828
    Secondary accession number(s): P52896
    , Q5SR15, Q7M4N2, Q9UCX2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: October 1, 1993
    Last modified: November 7, 2018
    This is version 192 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, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    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. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
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