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Protein

Aldo-keto reductase family 1 member B15

Gene

AKR1B15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei44 – 441NADPBy similarity
    Active sitei49 – 491Proton donorBy similarity
    Sitei78 – 781Lowers pKa of active site TyrBy similarity
    Binding sitei111 – 1111SubstrateBy similarity
    Binding sitei184 – 1841NADPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi20 – 223NADPBy similarity
    Nucleotide bindingi160 – 1612NADPBy similarity
    Nucleotide bindingi210 – 2178NADPBy similarity
    Nucleotide bindingi261 – 27313NADPBy similarityAdd
    BLAST

    GO - Molecular functioni

    • estradiol 17-beta-dehydrogenase activity Source: UniProtKB
    • oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    ReactomeiR-HSA-193144. Estrogen biosynthesis.

    Chemistry

    SwissLipidsiSLP:000001307. [C9JRZ8-1]

    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

    HGNCiHGNC:37281. AKR1B15.

    Subcellular locationi

    Isoform 1 :
    • Mitochondrion 1 Publication
    Isoform 2 :
    • Cytoplasmcytosol 1 Publication

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • mitochondrial matrix Source: Reactome
    • mitochondrion Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA165617622.

    Polymorphism and mutation databases

    BioMutaiAKR1B15.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 316316Aldo-keto reductase family 1 member B15PRO_0000395341Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei125 – 1251N6-acetyllysineBy similarity
    Modified residuei263 – 2631N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiC9JRZ8.
    PaxDbiC9JRZ8.
    PRIDEiC9JRZ8.

    PTM databases

    iPTMnetiC9JRZ8.
    PhosphoSiteiC9JRZ8.

    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.

    Organism-specific databases

    HPAiHPA020280.
    HPA073633.

    Interactioni

    Protein-protein interaction databases

    BioGridi137330. 11 interactions.
    STRINGi9606.ENSP00000389289.

    Structurei

    3D structure databases

    ProteinModelPortaliC9JRZ8.
    SMRiC9JRZ8. Positions 1-316.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldo/keto reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1577. Eukaryota.
    COG0656. LUCA.
    GeneTreeiENSGT00760000119041.
    HOGENOMiHOG000250272.
    InParanoidiC9JRZ8.
    OMAiQHEVGEA.
    OrthoDBiEOG091G0D69.
    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.
    PROSITEiPS00062. ALDOKETO_REDUCTASE_2. 1 hit.
    [Graphical view]

    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)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2222MATFV…LGTWR → MVLQMEPQVNSTNNFHQGPL DQPVGPLTGLKSSLLKDTTS AGPLLRPYPA in isoform 2. 2 PublicationsVSP_041606Add
    BLAST

    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.
    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

    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.
    UniGeneiHs.729418.

    3D structure databases

    ProteinModelPortaliC9JRZ8.
    SMRiC9JRZ8. Positions 1-316.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi137330. 11 interactions.
    STRINGi9606.ENSP00000389289.

    Chemistry

    SwissLipidsiSLP:000001307. [C9JRZ8-1]

    PTM databases

    iPTMnetiC9JRZ8.
    PhosphoSiteiC9JRZ8.

    Polymorphism and mutation databases

    BioMutaiAKR1B15.

    Proteomic databases

    MaxQBiC9JRZ8.
    PaxDbiC9JRZ8.
    PRIDEiC9JRZ8.

    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.
    GeneCardsiAKR1B15.
    HGNCiHGNC:37281. AKR1B15.
    HPAiHPA020280.
    HPA073633.
    MIMi616336. gene.
    neXtProtiNX_C9JRZ8.
    PharmGKBiPA165617622.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1577. Eukaryota.
    COG0656. LUCA.
    GeneTreeiENSGT00760000119041.
    HOGENOMiHOG000250272.
    InParanoidiC9JRZ8.
    OMAiQHEVGEA.
    OrthoDBiEOG091G0D69.
    TreeFamiTF106492.

    Enzyme and pathway databases

    ReactomeiR-HSA-193144. Estrogen biosynthesis.

    Miscellaneous databases

    GenomeRNAii441282.
    PROiC9JRZ8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000227471.

    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.
    PROSITEiPS00062. ALDOKETO_REDUCTASE_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAK1BF_HUMAN
    AccessioniPrimary (citable) accession number: C9JRZ8
    Secondary accession number(s): C9J3V2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 13, 2010
    Last sequence update: April 1, 2015
    Last modified: September 7, 2016
    This is version 60 of the entry and version 2 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

    Complete proteome, Reference proteome

    Documents

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