AK1D1_RABIT
ID AK1D1_RABIT Reviewed; 326 AA.
AC Q9TV64;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Aldo-keto reductase family 1 member D1;
DE EC=1.3.1.3 {ECO:0000250|UniProtKB:P51857};
DE AltName: Full=3-oxo-5-beta-steroid 4-dehydrogenase;
DE AltName: Full=Delta(4)-3-ketosteroid 5-beta-reductase;
DE AltName: Full=Delta(4)-3-oxosteroid 5-beta-reductase;
GN Name=AKR1D1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Liver;
RA Yamada M., Setoguchi Y., Setoguchi T.;
RT "Delta4-3-oxosteroid 5beta-reductase.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the stereospecific NADPH-dependent reduction of the
CC C4-C5 double bond of bile acid intermediates and steroid hormones
CC carrying a delta(4)-3-one structure to yield an A/B cis-ring junction.
CC This cis-configuration is crucial for bile acid biosynthesis and plays
CC important roles in steroid metabolism. Capable of reducing a broad
CC range of delta-(4)-3-ketosteroids from C18 (such as, 17beta-
CC hydroxyestr-4-en-3-one) to C27 (such as, 7alpha-hydroxycholest-4-en-3-
CC one). {ECO:0000250|UniProtKB:P51857}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestan-3-one + NADP(+) = cholest-4-en-3-one + H(+) +
CC NADPH; Xref=Rhea:RHEA:11524, ChEBI:CHEBI:15378, ChEBI:CHEBI:16074,
CC ChEBI:CHEBI:16175, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.3;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11526;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,5beta-dihydrocortisone + NADP(+) = cortisone + H(+) + NADPH;
CC Xref=Rhea:RHEA:14037, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962,
CC ChEBI:CHEBI:18093, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.3;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14039;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisol + H(+) + NADPH = 5beta-dihydrocortisol + NADP(+);
CC Xref=Rhea:RHEA:46644, ChEBI:CHEBI:732, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17650, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46645;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=corticosterone + H(+) + NADPH = 5beta-dihydrocorticosterone +
CC NADP(+); Xref=Rhea:RHEA:46664, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:86381;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46665;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha,12alpha-dihydroxycholest-4-en-3-one + H(+) + NADPH =
CC 7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADP(+);
CC Xref=Rhea:RHEA:46632, ChEBI:CHEBI:2288, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28477, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46633;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha-hydroxycholest-4-en-3-one + H(+) + NADPH = 7alpha-
CC hydroxy-5beta-cholestan-3-one + NADP(+); Xref=Rhea:RHEA:46640,
CC ChEBI:CHEBI:2290, ChEBI:CHEBI:15378, ChEBI:CHEBI:17899,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46641;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=epitestosterone + H(+) + NADPH = 5beta-dihydroepitestosterone
CC + NADP(+); Xref=Rhea:RHEA:46652, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:42534, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:86377; Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46653;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,17-dione + H(+) + NADPH = 5beta-androstane-
CC 3,17-dione + NADP(+); Xref=Rhea:RHEA:46656, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16422, ChEBI:CHEBI:16985, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46657;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + progesterone = 5beta-pregnan-3,20-dione +
CC NADP(+); Xref=Rhea:RHEA:46660, ChEBI:CHEBI:15378, ChEBI:CHEBI:17026,
CC ChEBI:CHEBI:30154, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46661;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=21-hydroxyprogesterone + H(+) + NADPH = 5beta-
CC dihydrodeoxycorticosterone + NADP(+); Xref=Rhea:RHEA:46668,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16973, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:86384;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46669;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=aldosterone + H(+) + NADPH = 5beta-dihydroaldosterone +
CC NADP(+); Xref=Rhea:RHEA:46672, ChEBI:CHEBI:15378, ChEBI:CHEBI:27584,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:86389;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46673;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxyandrosta-1,4-dien-3-one + H(+) + NADPH = 17beta-
CC hydroxy-5beta-androst-1-en-3-one + NADP(+); Xref=Rhea:RHEA:47076,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:34584, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87331;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47077;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxyestr-4-en-3-one + H(+) + NADPH = 17beta-hydroxy-
CC 5beta-estran-3-one + NADP(+); Xref=Rhea:RHEA:47080, ChEBI:CHEBI:7466,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:87333; Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47081;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-dihydrotestosterone + NADP(+) = H(+) + NADPH +
CC testosterone; Xref=Rhea:RHEA:46636, ChEBI:CHEBI:2150,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17347, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.3;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46637;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,11,17-trione + H(+) + NADPH = 17beta-
CC hydroxyandrost-4-ene-3,11-dione + NADP(+); Xref=Rhea:RHEA:53484,
CC ChEBI:CHEBI:2495, ChEBI:CHEBI:15378, ChEBI:CHEBI:34133,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53485;
CC Evidence={ECO:0000250|UniProtKB:P51857};
CC -!- ACTIVITY REGULATION: Subject to inhibition by high substrate
CC concentrations. Inhibited by testosterone concentrations above 10 uM.
CC Inhibited by the primary and secondary bile acids chenodeoxycholic acid
CC and ursodeoxycholic acid. {ECO:0000250|UniProtKB:P51857}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P51857}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; AB023951; BAA82867.1; -; mRNA.
DR RefSeq; NP_001075466.1; NM_001081997.1.
DR AlphaFoldDB; Q9TV64; -.
DR SMR; Q9TV64; -.
DR STRING; 9986.ENSOCUP00000014594; -.
DR PRIDE; Q9TV64; -.
DR GeneID; 100008612; -.
DR KEGG; ocu:100008612; -.
DR CTD; 6718; -.
DR eggNOG; KOG1577; Eukaryota.
DR InParanoid; Q9TV64; -.
DR OrthoDB; 1016440at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0047787; F:delta4-3-oxosteroid 5beta-reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0006699; P:bile acid biosynthetic process; IEA:InterPro.
DR GO; GO:0030573; P:bile acid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR CDD; cd19109; AKR_AKR1D1-3; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044483; AKR1D1.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE 2: Evidence at transcript level;
KW Bile acid catabolism; Cytoplasm; Lipid degradation; Lipid metabolism; NADP;
KW Oxidoreductase; Reference proteome; Steroid metabolism.
FT CHAIN 1..326
FT /note="Aldo-keto reductase family 1 member D1"
FT /id="PRO_0000124671"
FT ACT_SITE 58
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 22..26
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 26
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 58
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 89
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 120
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 132
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 169..170
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 219..224
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 230
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P51857"
FT BINDING 273..283
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P51857"
SQ SEQUENCE 326 AA; 37491 MW; DA7618FFC3F849AC CRC64;
MDLSATNHRI PLGDGNSIPI IGLGTYSEPK TTPKGSCATS VKIAIDTGYR HIDGAYIYQN
EHEVGETFRE KIAEGKVRRE DIFYCGKLWA TNHDPVMVRP TLERTLKVLK LDYIDLYIIE
IPMAFKPGDV VYPRDENGKW LYHKTNLCAT WEALEACKDA GLVKSLGVSN FNRQQLELLL
NKPGLKHKPV CNQVECHPYF TQPKLLKFCQ QHDIIIVAYS PLGTCRNPMW VNTSLPPLLK
DTLLNSLGKK YKKTAAQIVL RFNVQRGVVV IPKSFNPERI KENFQIFDFS LTEEEMKDIE
ALNKNVRYVE LLMWRDHPEY PFNDEY
