AK1C1_MACFU
ID AK1C1_MACFU Reviewed; 323 AA.
AC Q95JH6;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Aldo-keto reductase family 1 member C1 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.- {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.112 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.209 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.210 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.357 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.51 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.53 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:Q04828};
DE EC=1.3.1.20 {ECO:0000250|UniProtKB:Q04828};
DE AltName: Full=20-alpha-hydroxysteroid dehydrogenase;
DE Short=20-alpha-HSD;
DE EC=1.1.1.149 {ECO:0000250|UniProtKB:Q04828};
DE AltName: Full=Dihydrodiol dehydrogenase 1;
DE Short=DD-1;
DE Short=DD1;
GN Name=AKR1C1;
OS Macaca fuscata fuscata (Japanese macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9543;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=15618685; DOI=10.2133/dmpk.17.348;
RA Higaki Y., Kamiya T., Usami N., Shintani S., Shiraishi H., Ishikura S.,
RA Yamamoto I., Hara A.;
RT "Molecular characterization of two monkey dihydrodiol dehydrogenases.";
RL Drug Metab. Pharmacokinet. 17:348-356(2002).
CC -!- FUNCTION: Cytosolic aldo-keto reductase that catalyzes the NADH and
CC NADPH-dependent reduction of ketosteroids to hydroxysteroids. Most
CC probably acts as a reductase in vivo since the oxidase activity
CC measured in vitro is inhibited by physiological concentrations of
CC NADPH. Displays a broad positional specificity acting on positions 3,
CC 17 and 20 of steroids and regulates the metabolism of hormones like
CC estrogens and androgens. May also reduce conjugated steroids such as
CC 5alpha-dihydrotestosterone sulfate. Displays affinity for bile acids.
CC {ECO:0000250|UniProtKB:Q04828}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:34783, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.357; Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxysteroid + NAD(+) = a 3-oxosteroid + H(+) +
CC NADH; Xref=Rhea:RHEA:34779, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.357; Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NADP(+) = 17alpha-
CC hydroxyprogesterone + H(+) + NADPH; Xref=Rhea:RHEA:15857,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16418, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.149;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15859;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NAD(+) = 17alpha-
CC hydroxyprogesterone + H(+) + NADH; Xref=Rhea:RHEA:15853,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16418, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.149;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15855;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20S)-hydroxypregn-4-en-3-one + NADP(+) = H(+) + NADPH +
CC progesterone; Xref=Rhea:RHEA:42112, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42114;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20S)-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH +
CC progesterone; Xref=Rhea:RHEA:42108, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42109;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol +
CC H(+) + NADPH; Xref=Rhea:RHEA:16729, ChEBI:CHEBI:10702,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18135, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.20;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-indan-1-ol + NAD(+) = H(+) + indan-1-one + NADH;
CC Xref=Rhea:RHEA:16317, ChEBI:CHEBI:15378, ChEBI:CHEBI:17404,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:156384;
CC EC=1.1.1.112; Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-indan-1-ol + NADP(+) = H(+) + indan-1-one + NADPH;
CC Xref=Rhea:RHEA:16321, ChEBI:CHEBI:15378, ChEBI:CHEBI:17404,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:156384;
CC EC=1.1.1.112; Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:42116,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:16297,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.210;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16299;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:42120,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42121;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:20377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.209;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20378;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + H(+) + NADPH =
CC 5alpha-androstane-3alpha,17beta-diol + NADP(+); Xref=Rhea:RHEA:42156,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42158;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 3alpha-
CC hydroxy-5alpha-androstan-17-one + H(+) + NADH; Xref=Rhea:RHEA:42124,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24617;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADPH; Xref=Rhea:RHEA:14981, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.51;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14982;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20alpha-hydroxy-5beta-pregnan-3-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:42168, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30154, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78666; Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42169;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:22944, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16229, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + H(+) + NADPH =
CC 3beta,20alpha-dihydroxy-5beta-pregnane + NADP(+);
CC Xref=Rhea:RHEA:65496, ChEBI:CHEBI:15378, ChEBI:CHEBI:16229,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:156526;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65497;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3beta,5alpha,17beta)-3-hydroxyandrostan-17-yl sulfate +
CC NADP(+) = 5alpha-dihydrotestosterone sulfate + H(+) + NADPH;
CC Xref=Rhea:RHEA:53120, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:136982, ChEBI:CHEBI:136983;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53122;
CC Evidence={ECO:0000250|UniProtKB:Q04828};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000250|UniProtKB:Q04828}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q04828}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q04828}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, adrenal gland, intestine and
CC kidney. {ECO:0000269|PubMed:15618685}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; AB070210; BAB63207.1; -; mRNA.
DR AlphaFoldDB; Q95JH6; -.
DR SMR; Q95JH6; -.
DR BRENDA; 1.3.1.20; 3123.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0047006; F:17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0033703; F:3beta-hydroxy-5beta-steroid dehydrogenase activity; IEA:RHEA.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047042; F:androsterone dehydrogenase (B-specific) activity; ISS:UniProtKB.
DR GO; GO:0032052; F:bile acid binding; ISS:UniProtKB.
DR GO; GO:0031406; F:carboxylic acid binding; ISS:UniProtKB.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047718; F:indanol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; IEA:UniProtKB-EC.
DR GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0008206; P:bile acid metabolic process; ISS:UniProtKB.
DR GO; GO:0007586; P:digestion; ISS:UniProtKB.
DR CDD; cd19108; AKR_AKR1C1-35; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044482; AKR1C.
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 Cytoplasm; Lipid metabolism; NADP; Oxidoreductase.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C1"
FT /id="PRO_0000124635"
FT ACT_SITE 55
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 20..24
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 24
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 50
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 117
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 166..167
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 216..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 222
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 227
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 270..280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 54
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000250"
FT SITE 84
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
SQ SEQUENCE 323 AA; 36963 MW; 01241BA544C43ED7 CRC64;
MDSKHQCVKL NDGHFMPVLG FGTYAPAEVP KNKAIEATKL AIEAGFRHID SAHLYNNEEY
VGLAIRSKIA DGTVKREDIF YTSKLWCNSH RPEFVRPALE RSLKNLQLDY VDLYLIHFPV
SLKPGEELIP KDENGKLLFD TVDLCATWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNKP
GLKYKPVCNQ VECHPYLNQR KLLDFCKSKD IVLVAYSALG SHREKPWVDQ NSPVLLEDPV
LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIREN MKVFEFQLTS EDMKAIDGLD
RNIRYLTLDI FAGPPNYPFS DEY
