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Protein

Aldo-keto reductase family 1 member C21

Gene

Akr1c21

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids.5 Publications

Catalytic activityi

Androsterone + NAD(P)+ = 5-alpha-androstane-3,17-dione + NAD(P)H.3 Publications

Enzyme regulationi

Inhibited by high concentrations of substrate.1 Publication

Kineticsi

  1. KM=1.8 µM for NADP2 Publications
  2. KM=19 µM for androstenedione2 Publications
  3. KM=0.5 µM for 5-beta-pregnane-3-alpha,20-alpha-diol2 Publications
  4. KM=0.5 µM for 5-beta-pregnane-3,20-dione2 Publications
  5. KM=0.6 µM for epitestosterone2 Publications
  6. KM=0.3 µM for androst-4-ene-3,17-dione2 Publications

    pH dependencei

    Optimum pH is 10.0.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei31Substrate1
    Binding sitei50NADP3 Publications1
    Active sitei55Proton donor1
    Sitei84Lowers pKa of active site TyrBy similarity1
    Binding sitei117Substrate1
    Binding sitei190NADP3 Publications1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi20 – 24NADP3 Publications5
    Nucleotide bindingi166 – 167NADP3 Publications2
    Nucleotide bindingi216 – 224NADP3 Publications9
    Nucleotide bindingi270 – 280NADP3 PublicationsAdd BLAST11

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Lipid metabolism, Steroid metabolism

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    BRENDAi1.1.1.148. 3474.
    1.1.1.209. 3474.
    1.1.1.50. 3474.
    ReactomeiR-MMU-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
    R-MMU-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
    R-MMU-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
    R-MMU-2162123. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    R-MMU-5365859. RA biosynthesis pathway.
    R-MMU-975634. Retinoid metabolism and transport.
    SABIO-RKQ91WR5.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aldo-keto reductase family 1 member C21 (EC:1.1.1.-)
    Alternative name(s):
    17-alpha-hydroxysteroid dehydrogenase
    Short name:
    17-alpha-HSD
    3(or 17)-alpha-hydroxysteroid dehydrogenase (EC:1.1.1.209)
    3-alpha-hydroxysteroid dehydrogenase
    Dihydrodiol dehydrogenase type 1
    Short name:
    DD1
    Dihydrodiol dehydrogenase type 3
    Short name:
    DD3
    Gene namesi
    Name:Akr1c21
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 13

    Organism-specific databases

    MGIiMGI:1924587. Akr1c21.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi24A → Y: Reduces enzyme activity and affinity for substrate. Alters the stereospecificity, so that androstenedione is converted to testosterone. 1 Publication1
    Mutagenesisi31K → A: No effect on affinity for androstenedione. Slight increase of catalytic activity. 1 Publication1
    Mutagenesisi222Q → N: Decreases affinity for NADP. Changes enzyme activity, leading to the production of testosterone and concomitantly reducing the production of epi-testosterone. 1 Publication1
    Mutagenesisi224Y → D: Decreases affinity for NADP. Changes enzyme activity, leading to the production of testosterone and concomitantly reducing the production of epi-testosterone. 1 Publication1
    Mutagenesisi224Y → F: No effect on enzyme activity. Decreases affinity for NADP. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL1075270.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003262221 – 323Aldo-keto reductase family 1 member C21Add BLAST323

    Proteomic databases

    MaxQBiQ91WR5.
    PaxDbiQ91WR5.
    PeptideAtlasiQ91WR5.
    PRIDEiQ91WR5.

    PTM databases

    iPTMnetiQ91WR5.
    PhosphoSitePlusiQ91WR5.

    Expressioni

    Tissue specificityi

    Detected in kidney and brain.2 Publications

    Gene expression databases

    BgeeiENSMUSG00000021207.
    CleanExiMM_AKR1C21.
    GenevisibleiQ91WR5. MM.

    Interactioni

    Subunit structurei

    Monomer.5 Publications

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000021628.

    Chemistry databases

    BindingDBiQ91WR5.

    Structurei

    Secondary structure

    1323
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi7 – 9Combined sources3
    Beta strandi15 – 22Combined sources8
    Beta strandi27 – 29Combined sources3
    Helixi33 – 44Combined sources12
    Beta strandi48 – 50Combined sources3
    Helixi53 – 55Combined sources3
    Helixi58 – 70Combined sources13
    Helixi76 – 78Combined sources3
    Beta strandi80 – 85Combined sources6
    Helixi87 – 89Combined sources3
    Turni92 – 94Combined sources3
    Helixi95 – 106Combined sources12
    Beta strandi111 – 117Combined sources7
    Beta strandi121 – 123Combined sources3
    Beta strandi125 – 129Combined sources5
    Helixi144 – 156Combined sources13
    Beta strandi159 – 167Combined sources9
    Helixi170 – 177Combined sources8
    Beta strandi187 – 192Combined sources6
    Beta strandi194 – 197Combined sources4
    Helixi200 – 208Combined sources9
    Beta strandi212 – 216Combined sources5
    Turni225 – 227Combined sources3
    Helixi228 – 231Combined sources4
    Helixi235 – 237Combined sources3
    Helixi239 – 248Combined sources10
    Helixi252 – 261Combined sources10
    Turni262 – 264Combined sources3
    Beta strandi266 – 269Combined sources4
    Helixi274 – 280Combined sources7
    Helixi281 – 285Combined sources5
    Helixi290 – 297Combined sources8
    Helixi309 – 311Combined sources3
    Beta strandi318 – 321Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HE5X-ray2.90A/B/C/D1-323[»]
    2HE8X-ray1.90A/B1-323[»]
    2HEJX-ray1.35A/B1-323[»]
    2IPFX-ray1.85A/B6-323[»]
    2IPGX-ray1.90A/B5-323[»]
    2P5NX-ray1.80A/B1-323[»]
    3CV6X-ray2.10A/B1-323[»]
    3FJNX-ray2.30A/B1-323[»]
    DisProtiDP00690.
    ProteinModelPortaliQ91WR5.
    SMRiQ91WR5.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ91WR5.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the aldo/keto reductase family.Curated

    Phylogenomic databases

    eggNOGiKOG1577. Eukaryota.
    COG0656. LUCA.
    GeneTreeiENSGT00760000119041.
    HOGENOMiHOG000250272.
    HOVERGENiHBG000020.
    InParanoidiQ91WR5.
    OMAiNTEDHVG.
    OrthoDBiEOG091G0D69.
    PhylomeDBiQ91WR5.
    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]

    Sequencei

    Sequence statusi: Complete.

    Q91WR5-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MNSKCHCVIL NDGNFIPVLG FGTALPLECP KSKAKELTKI AIDAGFHHFD
    60 70 80 90 100
    SASVYNTEDH VGEAIRSKIA DGTVRREDIF YTSKVWCTSL HPELVRASLE
    110 120 130 140 150
    RSLQKLQFDY VDLYLIHYPM ALKPGEENFP VDEHGKLIFD RVDLCATWEA
    160 170 180 190 200
    MEKCKDAGLT KSIGVSNFNY RQLEMILNKP GLKYKPVCNQ VECHPYLNQM
    210 220 230 240 250
    KLLDFCKSKD IVLVAYGVLG TQRYGGWVDQ NSPVLLDEPV LGSMAKKYNR
    260 270 280 290 300
    TPALIALRYQ LQRGIVVLNT SLKEERIKEN MQVFEFQLSS EDMKVLDGLN
    310 320
    RNMRYIPAAI FKGHPNWPFL DEY
    Length:323
    Mass (Da):36,877
    Last modified:March 18, 2008 - v2
    Checksum:i0D598A0559EFBF11
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti27L → V in BAD18929 (PubMed:15577209).Curated1
    Sequence conflicti27L → V in AAH13531 (PubMed:15489334).Curated1
    Sequence conflicti27L → V in AAH91761 (PubMed:15489334).Curated1
    Sequence conflicti60H → R in BAD18929 (PubMed:15577209).Curated1
    Sequence conflicti60H → R in AAH13531 (PubMed:15489334).Curated1
    Sequence conflicti60H → R in AAH91761 (PubMed:15489334).Curated1
    Sequence conflicti91H → R in BAD18929 (PubMed:15577209).Curated1
    Sequence conflicti91H → R in AAH13531 (PubMed:15489334).Curated1
    Sequence conflicti91H → R in AAH91761 (PubMed:15489334).Curated1
    Sequence conflicti100E → V in BAD18929 (PubMed:15577209).Curated1
    Sequence conflicti100E → V in AAH13531 (PubMed:15489334).Curated1
    Sequence conflicti100E → V in AAH91761 (PubMed:15489334).Curated1
    Sequence conflicti170Y → S in BAD18929 (PubMed:15577209).Curated1
    Sequence conflicti170Y → S in AAH13531 (PubMed:15489334).Curated1
    Sequence conflicti170Y → S in AAH91761 (PubMed:15489334).Curated1
    Sequence conflicti294K → E in AAH61057 (PubMed:15489334).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB178898 mRNA. Translation: BAD18929.1.
    AY742217 mRNA. Translation: AAW65159.1.
    AK020439 mRNA. Translation: BAB32101.1.
    BC013531 mRNA. Translation: AAH13531.1.
    BC061057 mRNA. Translation: AAH61057.1.
    BC091761 mRNA. Translation: AAH91761.1.
    CCDSiCCDS26225.1.
    RefSeqiNP_084177.2. NM_029901.2.
    UniGeneiMm.27085.

    Genome annotation databases

    EnsembliENSMUST00000021628; ENSMUSP00000021628; ENSMUSG00000021207.
    GeneIDi77337.
    KEGGimmu:77337.
    UCSCiuc007pjr.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB178898 mRNA. Translation: BAD18929.1.
    AY742217 mRNA. Translation: AAW65159.1.
    AK020439 mRNA. Translation: BAB32101.1.
    BC013531 mRNA. Translation: AAH13531.1.
    BC061057 mRNA. Translation: AAH61057.1.
    BC091761 mRNA. Translation: AAH91761.1.
    CCDSiCCDS26225.1.
    RefSeqiNP_084177.2. NM_029901.2.
    UniGeneiMm.27085.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HE5X-ray2.90A/B/C/D1-323[»]
    2HE8X-ray1.90A/B1-323[»]
    2HEJX-ray1.35A/B1-323[»]
    2IPFX-ray1.85A/B6-323[»]
    2IPGX-ray1.90A/B5-323[»]
    2P5NX-ray1.80A/B1-323[»]
    3CV6X-ray2.10A/B1-323[»]
    3FJNX-ray2.30A/B1-323[»]
    DisProtiDP00690.
    ProteinModelPortaliQ91WR5.
    SMRiQ91WR5.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000021628.

    Chemistry databases

    BindingDBiQ91WR5.
    ChEMBLiCHEMBL1075270.

    PTM databases

    iPTMnetiQ91WR5.
    PhosphoSitePlusiQ91WR5.

    Proteomic databases

    MaxQBiQ91WR5.
    PaxDbiQ91WR5.
    PeptideAtlasiQ91WR5.
    PRIDEiQ91WR5.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000021628; ENSMUSP00000021628; ENSMUSG00000021207.
    GeneIDi77337.
    KEGGimmu:77337.
    UCSCiuc007pjr.1. mouse.

    Organism-specific databases

    CTDi77337.
    MGIiMGI:1924587. Akr1c21.

    Phylogenomic databases

    eggNOGiKOG1577. Eukaryota.
    COG0656. LUCA.
    GeneTreeiENSGT00760000119041.
    HOGENOMiHOG000250272.
    HOVERGENiHBG000020.
    InParanoidiQ91WR5.
    OMAiNTEDHVG.
    OrthoDBiEOG091G0D69.
    PhylomeDBiQ91WR5.
    TreeFamiTF106492.

    Enzyme and pathway databases

    BRENDAi1.1.1.148. 3474.
    1.1.1.209. 3474.
    1.1.1.50. 3474.
    ReactomeiR-MMU-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
    R-MMU-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
    R-MMU-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
    R-MMU-2162123. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    R-MMU-5365859. RA biosynthesis pathway.
    R-MMU-975634. Retinoid metabolism and transport.
    SABIO-RKQ91WR5.

    Miscellaneous databases

    EvolutionaryTraceiQ91WR5.
    PROiQ91WR5.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000021207.
    CleanExiMM_AKR1C21.
    GenevisibleiQ91WR5. MM.

    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 nameiAK1CL_MOUSE
    AccessioniPrimary (citable) accession number: Q91WR5
    Secondary accession number(s): Q6P8V0, Q9CX32
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 18, 2008
    Last sequence update: March 18, 2008
    Last modified: November 2, 2016
    This is version 110 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    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.