AKC1H_RAT
ID AKC1H_RAT Reviewed; 323 AA.
AC P51652; Q498E4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Aldo-keto reductase family 1 member C18;
DE EC=1.1.-.-;
DE AltName: Full=20-alpha-hydroxysteroid dehydrogenase;
DE Short=20-alpha-HSD;
DE EC=1.1.1.149;
DE AltName: Full=HSD1;
GN Name=Akr1c18;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 257-269 AND 315-323.
RC STRAIN=Sprague-Dawley; TISSUE=Corpus luteum;
RX PubMed=8024573; DOI=10.1006/bbrc.1994.1844;
RA Mao J., Duan W.R., Albarracin C.T., Parmer T.G., Gibori G.;
RT "Isolation and characterization of a rat luteal cDNA encoding 20 alpha-
RT hydroxysteroid dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 201:1289-1295(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar Imamichi; TISSUE=Ovary;
RX PubMed=8172618; DOI=10.1042/bj2990561;
RA Miura R., Shiota K., Noda K., Yagi S., Ogawa T., Takahashi M.;
RT "Molecular cloning of cDNA for rat ovarian 20 alpha-hydroxysteroid
RT dehydrogenase (HSD1).";
RL Biochem. J. 299:561-567(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 233-243; 252-269 AND 315-323.
RC STRAIN=Sprague-Dawley; TISSUE=Corpus luteum;
RX PubMed=8194472; DOI=10.1210/endo.134.6.8194472;
RA Albarracin C.T., Parmer T.G., Duan W.R., Nelson S.E., Gibori G.;
RT "Identification of a major prolactin-regulated protein as 20 alpha-
RT hydroxysteroid dehydrogenase: coordinate regulation of its activity,
RT protein content, and messenger ribonucleic acid expression.";
RL Endocrinology 134:2453-2460(1994).
RN [5]
RP PROTEIN SEQUENCE OF 3-21.
RA Noda K., Shiota K., Ogawa T., Yagi S., Takahashi M.;
RL J. Reprod. Dev. 39:169-173(1993).
CC -!- FUNCTION: Catalyzes the conversion of progesterone into 20-alpha-
CC dihydroprogesterone (20 alpha-OHP).
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 -!- 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 -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Corpus luteum (large luteal cells).
CC -!- DEVELOPMENTAL STAGE: Remains repressed throughout pregnancy and becomes
CC highly and rapidly expressed before parturition.
CC -!- INDUCTION: Repressed by prolactin.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; L32601; AAA40601.1; -; mRNA.
DR EMBL; D14424; BAA03317.1; -; mRNA.
DR EMBL; BC100248; AAI00249.1; -; mRNA.
DR PIR; JC2330; JC2330.
DR RefSeq; NP_612519.1; NM_138510.1.
DR AlphaFoldDB; P51652; -.
DR SMR; P51652; -.
DR STRING; 10116.ENSRNOP00000023739; -.
DR jPOST; P51652; -.
DR PaxDb; P51652; -.
DR Ensembl; ENSRNOT00000023739; ENSRNOP00000023739; ENSRNOG00000017531.
DR GeneID; 171516; -.
DR KEGG; rno:171516; -.
DR UCSC; RGD:708428; rat.
DR CTD; 8644; -.
DR RGD; 708428; Akr1c18.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000153677; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; P51652; -.
DR OMA; TKLPNQH; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; P51652; -.
DR TreeFam; TF106492; -.
DR PRO; PR:P51652; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000017531; Expressed in ovary and 9 other tissues.
DR Genevisible; P51652; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; ISO:RGD.
DR GO; GO:0047006; F:17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; IDA:RGD.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:RGD.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IDA:RGD.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; ISO:RGD.
DR GO; GO:0032052; F:bile acid binding; IBA:GO_Central.
DR GO; GO:0047787; F:delta4-3-oxosteroid 5beta-reductase activity; ISO:RGD.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; ISO:RGD.
DR GO; GO:0045550; F:geranylgeranyl reductase activity; ISO:RGD.
DR GO; GO:0045703; F:ketoreductase activity; ISO:RGD.
DR GO; GO:0047086; F:ketosteroid monooxygenase activity; ISO:RGD.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISO:RGD.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; ISO:RGD.
DR GO; GO:0018636; F:phenanthrene 9,10-monooxygenase activity; ISO:RGD.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISO:RGD.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR GO; GO:0071384; P:cellular response to corticosteroid stimulus; ISO:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:1904322; P:cellular response to forskolin; IEP:RGD.
DR GO; GO:0097211; P:cellular response to gonadotropin-releasing hormone; IEP:RGD.
DR GO; GO:0071395; P:cellular response to jasmonic acid stimulus; ISO:RGD.
DR GO; GO:1990646; P:cellular response to prolactin; IEP:RGD.
DR GO; GO:0071799; P:cellular response to prostaglandin D stimulus; ISO:RGD.
DR GO; GO:0071379; P:cellular response to prostaglandin stimulus; ISO:RGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IMP:RGD.
DR GO; GO:0044597; P:daunorubicin metabolic process; ISO:RGD.
DR GO; GO:0044598; P:doxorubicin metabolic process; ISO:RGD.
DR GO; GO:0016488; P:farnesol catabolic process; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:RGD.
DR GO; GO:0043170; P:macromolecule metabolic process; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; ISO:RGD.
DR GO; GO:1900053; P:negative regulation of retinoic acid biosynthetic process; ISO:RGD.
DR GO; GO:0007567; P:parturition; ISO:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0006709; P:progesterone catabolic process; ISO:RGD.
DR GO; GO:0042448; P:progesterone metabolic process; IDA:RGD.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD.
DR GO; GO:0048385; P:regulation of retinoic acid receptor signaling pathway; ISO:RGD.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IDA:RGD.
DR GO; GO:2000224; P:regulation of testosterone biosynthetic process; ISO:RGD.
DR GO; GO:0007584; P:response to nutrient; ISO:RGD.
DR GO; GO:0042574; P:retinal metabolic process; ISO:RGD.
DR GO; GO:0008202; P:steroid metabolic process; ISO:RGD.
DR GO; GO:0061370; P:testosterone biosynthetic process; ISO:RGD.
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 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C18"
FT /id="PRO_0000124650"
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 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..221
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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"
FT CONFLICT 242
FT /note="C -> L (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 37300 MW; D14270961515195E CRC64;
MNSKIQKMEL NDGHSIPVLG FGTYATEENL RKKSMESTKI AIDVGFRHID CSHLYQNEEE
IGQAIVSKIE DGTVKREDIF YTSKLWSTSH RPELVRPSLE NSLRKLNLDY VDLYLIHFPV
SLKPGDELLP QDEHGNLILD TVDLCDTWEA MEKCKDAGLA KSIGVSNFNR RQLEKILNKP
GLKHRPVCNQ VECHLYLNQS KLLAYCKMND IVLVAYGALG TQRYKYCINE DTPVLLDDPI
LCTMAKKYKR TPALIALRYQ LERGIVTLVK SFNEERIREN LQVFDFQLAS DDMEILDNLD
RNLRYFPANM FKAHPNFPFS DEY
