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Protein

Aldo-keto reductase family 1 member B15

Gene

AKR1B15

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

Functioni

Isoform 1: Mainly acts as a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (shows 17-beta-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoAs. Has a strong selectivity towards NADP(H) (PubMed:25577493).2 Publications
Isoform 2: No oxidoreductase activity observed with the tested substrates.1 Publication

Catalytic activityi

17-beta-estradiol + NAD(P)+ = estrone + NAD(P)H.1 Publication

Kineticsi

kcat is 1.7 min(-1) using isoform 1 for the reduction of androsterone. kcat is 1.1 min(-1) using isoform 1 for the reduction of delta-4-androstenedione. kcat is 1.0 min(-1) using isoform 1 for the reduction of estrone. kcat is 0.5 min(-1) using isoform 1 for the reduction of acetoacetyl-CoA. kcat is 3.0 min(-1) using isoform 1 for the oxidation of 3-alpha,17-beta-androstandiol. kcat is 0.6 min(-1) using isoform 1 for the oxidation of testosterone. kcat is 0.5 min(-1) using isoform 1 for the oxidation of 17-beta-estradiol.1 Publication
  1. KM=2.8 µM for androsterone (tested with isoform 1 in the reductive reaction)1 Publication
  2. KM=1.9 µM for delta-4-androstenedione (tested with isoform 1 in the reductive reaction)1 Publication
  3. KM=2.5 µM for estrone (tested with isoform 1 in the reductive reaction)1 Publication
  4. KM=63.4 µM for acetoacetyl-CoA (tested with isoform 1 in the reductive reaction)1 Publication
  5. KM=19.2 µM for 3-alpha,17-beta-androstandiol (tested with isoform 1 in the oxidative reaction)1 Publication
  6. KM=7.1 µM for testosterone (tested with isoform 1 in the oxidative reaction)1 Publication
  7. KM=9.1 µM for 17-beta-estradiol (tested with isoform 1 in the oxidative reaction)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei44NADPBy similarity1
    Active sitei49Proton donorBy similarity1
    Sitei78Lowers pKa of active site TyrBy similarity1
    Binding sitei111SubstrateBy similarity1
    Binding sitei184NADPBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi20 – 22NADPBy similarity3
    Nucleotide bindingi160 – 161NADPBy similarity2
    Nucleotide bindingi210 – 217NADPBy similarity8
    Nucleotide bindingi261 – 273NADPBy similarityAdd BLAST13

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    LigandNADP

    Enzyme and pathway databases

    ReactomeiR-HSA-193144 Estrogen biosynthesis

    Chemistry databases

    SwissLipidsiSLP:000001307 [C9JRZ8-1]
    SLP:000001874 [C9JRZ8-2]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aldo-keto reductase family 1 member B15Curated (EC:1.1.1.-1 Publication)
    Alternative name(s):
    Estradiol 17-beta-dehydrogenase AKR1B15Curated (EC:1.1.1.621 Publication)
    Gene namesi
    Name:AKR1B15Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000227471.8
    HGNCiHGNC:37281 AKR1B15
    MIMi616336 gene
    neXtProtiNX_C9JRZ8

    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, Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    OpenTargetsiENSG00000227471
    PharmGKBiPA165617622

    Polymorphism and mutation databases

    BioMutaiAKR1B15

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003953411 – 316Aldo-keto reductase family 1 member B15Add BLAST316

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei125N6-acetyllysineBy similarity1
    Modified residuei263N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiC9JRZ8
    MaxQBiC9JRZ8
    PaxDbiC9JRZ8
    PRIDEiC9JRZ8
    ProteomicsDBi11424
    11425 [C9JRZ8-2]

    PTM databases

    iPTMnetiC9JRZ8
    PhosphoSitePlusiC9JRZ8

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed at highest levels in steroid-sensitive tissues, such as placenta, testis and adipose tissue.1 Publication

    Gene expression databases

    BgeeiENSG00000227471 Expressed in 60 organ(s), highest expression level in gastrocnemius

    Organism-specific databases

    HPAiHPA020280
    HPA073633

    Interactioni

    Protein-protein interaction databases

    BioGridi137330, 11 interactors
    IntActiC9JRZ8, 1 interactor
    STRINGi9606.ENSP00000389289

    Structurei

    3D structure databases

    ProteinModelPortaliC9JRZ8
    SMRiC9JRZ8
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldo/keto reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1577 Eukaryota
    COG0656 LUCA
    GeneTreeiENSGT00760000119041
    HOGENOMiHOG000250272
    InParanoidiC9JRZ8
    OMAiTHPEGVY
    OrthoDBiEOG091G0D69
    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
    PS00062 ALDOKETO_REDUCTASE_2, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
    Isoform 1 (identifier: C9JRZ8-1) [UniParc]FASTAAdd to basket
    Also known as: AKR1B15.11 Publication

    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
    MATFVELSTK AKMPIVGLGT WRSLLGKVKE AVKVAIDAEY RHIDCAYFYE
    60 70 80 90 100
    NQHEVGEAIQ EKIQEKAVMR EDLFIVSKVW PTFFERPLVR KAFEKTLKDL
    110 120 130 140 150
    KLSYLDVYLI HWPQGFKTGD DFFPKDDKGN MISGKGTFLD AWEAMEELVD
    160 170 180 190 200
    EGLVKALGVS NFNHFQIERL LNKPGLKYKP VTNQVECHPY LTQEKLIQYC
    210 220 230 240 250
    HSKGITVTAY SPLGSPDRPW AKPEDPSLLE DPKIKEIAAK HKKTTAQVLI
    260 270 280 290 300
    RFHIQRNVTV IPKSMTPAHI VENIQVFDFK LSDEEMATIL SFNRNWRAFD
    310
    FKEFSHLEDF PFDAEY
    Length:316
    Mass (Da):36,537
    Last modified:April 1, 2015 - v2
    Checksum:i5FB6CBFA7190C740
    GO
    Isoform 2 (identifier: C9JRZ8-2) [UniParc]FASTAAdd to basket
    Also known as: AKR1B15.21 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         1-22: MATFVELSTKAKMPIVGLGTWR → MVLQMEPQVNSTNNFHQGPLDQPVGPLTGLKSSLLKDTTSAGPLLRPYPA

    Note: No experimental confirmation available.
    Show »
    Length:344
    Mass (Da):39,460
    Checksum:iA130BB8231C4C946
    GO

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0416061 – 22MATFV…LGTWR → MVLQMEPQVNSTNNFHQGPL DQPVGPLTGLKSSLLKDTTS AGPLLRPYPA in isoform 2. 2 PublicationsAdd BLAST22

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AC078847 Genomic DNA No translation available.
    CH471070 Genomic DNA Translation: EAW83819.1
    CCDSiCCDS47715.2 [C9JRZ8-2]
    RefSeqiNP_001074007.2, NM_001080538.2 [C9JRZ8-2]
    XP_011514543.2, XM_011516241.2 [C9JRZ8-1]
    XP_016867713.1, XM_017012224.1 [C9JRZ8-2]
    UniGeneiHs.729418

    Genome annotation databases

    EnsembliENST00000423958; ENSP00000397009; ENSG00000227471 [C9JRZ8-2]
    ENST00000457545; ENSP00000389289; ENSG00000227471 [C9JRZ8-2]
    GeneIDi441282
    KEGGihsa:441282
    UCSCiuc011kpr.3 human [C9JRZ8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AC078847 Genomic DNA No translation available.
    CH471070 Genomic DNA Translation: EAW83819.1
    CCDSiCCDS47715.2 [C9JRZ8-2]
    RefSeqiNP_001074007.2, NM_001080538.2 [C9JRZ8-2]
    XP_011514543.2, XM_011516241.2 [C9JRZ8-1]
    XP_016867713.1, XM_017012224.1 [C9JRZ8-2]
    UniGeneiHs.729418

    3D structure databases

    ProteinModelPortaliC9JRZ8
    SMRiC9JRZ8
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi137330, 11 interactors
    IntActiC9JRZ8, 1 interactor
    STRINGi9606.ENSP00000389289

    Chemistry databases

    SwissLipidsiSLP:000001307 [C9JRZ8-1]
    SLP:000001874 [C9JRZ8-2]

    PTM databases

    iPTMnetiC9JRZ8
    PhosphoSitePlusiC9JRZ8

    Polymorphism and mutation databases

    BioMutaiAKR1B15

    Proteomic databases

    EPDiC9JRZ8
    MaxQBiC9JRZ8
    PaxDbiC9JRZ8
    PRIDEiC9JRZ8
    ProteomicsDBi11424
    11425 [C9JRZ8-2]

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000423958; ENSP00000397009; ENSG00000227471 [C9JRZ8-2]
    ENST00000457545; ENSP00000389289; ENSG00000227471 [C9JRZ8-2]
    GeneIDi441282
    KEGGihsa:441282
    UCSCiuc011kpr.3 human [C9JRZ8-1]

    Organism-specific databases

    CTDi441282
    EuPathDBiHostDB:ENSG00000227471.8
    GeneCardsiAKR1B15
    HGNCiHGNC:37281 AKR1B15
    HPAiHPA020280
    HPA073633
    MIMi616336 gene
    neXtProtiNX_C9JRZ8
    OpenTargetsiENSG00000227471
    PharmGKBiPA165617622
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1577 Eukaryota
    COG0656 LUCA
    GeneTreeiENSGT00760000119041
    HOGENOMiHOG000250272
    InParanoidiC9JRZ8
    OMAiTHPEGVY
    OrthoDBiEOG091G0D69
    TreeFamiTF106492

    Enzyme and pathway databases

    ReactomeiR-HSA-193144 Estrogen biosynthesis

    Miscellaneous databases

    GenomeRNAii441282
    PROiPR:C9JRZ8
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000227471 Expressed in 60 organ(s), highest expression level in gastrocnemius

    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
    PS00062 ALDOKETO_REDUCTASE_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAK1BF_HUMAN
    AccessioniPrimary (citable) accession number: C9JRZ8
    Secondary accession number(s): C9J3V2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 13, 2010
    Last sequence update: April 1, 2015
    Last modified: November 7, 2018
    This is version 75 of the entry and version 2 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

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
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