AKC1H_MOUSE
ID AKC1H_MOUSE Reviewed; 323 AA.
AC Q8K023; Q99N44;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
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;
GN Name=Akr1c18;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Ovary;
RA Ishida M., Chang K., Hirabayashi K., Nishihara M., Takahashi M.;
RT "Cloning of mouse 20alpha-hydroxysteroid dehydrogenase cDNA and its mRNA
RT localization during pregnancy.";
RL J. Reprod. Dev. 45:321-329(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K023-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K023-2; Sequence=VSP_014039;
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; AB059565; BAB40958.1; -; mRNA.
DR EMBL; BC034259; AAH34259.1; -; mRNA.
DR CCDS; CCDS26219.1; -. [Q8K023-1]
DR CCDS; CCDS84006.1; -. [Q8K023-2]
DR RefSeq; NP_001333464.1; NM_001346535.1. [Q8K023-2]
DR RefSeq; NP_598827.1; NM_134066.2. [Q8K023-1]
DR AlphaFoldDB; Q8K023; -.
DR SMR; Q8K023; -.
DR IntAct; Q8K023; 1.
DR STRING; 10090.ENSMUSP00000021635; -.
DR iPTMnet; Q8K023; -.
DR PhosphoSitePlus; Q8K023; -.
DR jPOST; Q8K023; -.
DR MaxQB; Q8K023; -.
DR PaxDb; Q8K023; -.
DR PeptideAtlas; Q8K023; -.
DR PRIDE; Q8K023; -.
DR ProteomicsDB; 282063; -. [Q8K023-1]
DR ProteomicsDB; 282064; -. [Q8K023-2]
DR DNASU; 105349; -.
DR Ensembl; ENSMUST00000021635; ENSMUSP00000021635; ENSMUSG00000021214. [Q8K023-1]
DR Ensembl; ENSMUST00000110704; ENSMUSP00000106332; ENSMUSG00000021214. [Q8K023-2]
DR GeneID; 105349; -.
DR KEGG; mmu:105349; -.
DR UCSC; uc007pjj.1; mouse. [Q8K023-1]
DR UCSC; uc007pjk.1; mouse. [Q8K023-2]
DR CTD; 105349; -.
DR MGI; MGI:2145420; Akr1c18.
DR VEuPathDB; HostDB:ENSMUSG00000021214; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000153677; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; Q8K023; -.
DR OMA; TKLPNQH; -.
DR PhylomeDB; Q8K023; -.
DR TreeFam; TF106492; -.
DR BRENDA; 1.1.1.149; 3474.
DR BioGRID-ORCS; 105349; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q8K023; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8K023; protein.
DR Bgee; ENSMUSG00000021214; Expressed in skin of external ear and 66 other tissues.
DR ExpressionAtlas; Q8K023; baseline and differential.
DR Genevisible; Q8K023; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; ISO:MGI.
DR GO; GO:0047006; F:17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; IDA:MGI.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; ISO:MGI.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; ISO:MGI.
DR GO; GO:0047042; F:androsterone dehydrogenase (B-specific) activity; ISO:MGI.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; ISO:MGI.
DR GO; GO:0032052; F:bile acid binding; ISO:MGI.
DR GO; GO:0031406; F:carboxylic acid binding; ISO:MGI.
DR GO; GO:0047743; F:chlordecone reductase activity; ISO:MGI.
DR GO; GO:0047787; F:delta4-3-oxosteroid 5beta-reductase activity; ISO:MGI.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; ISO:MGI.
DR GO; GO:0045550; F:geranylgeranyl reductase activity; ISO:MGI.
DR GO; GO:0045703; F:ketoreductase activity; ISO:MGI.
DR GO; GO:0047086; F:ketosteroid monooxygenase activity; ISO:MGI.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISO:MGI.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; ISO:MGI.
DR GO; GO:0018636; F:phenanthrene 9,10-monooxygenase activity; ISO:MGI.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISO:MGI.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; ISO:MGI.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:1904322; P:cellular response to forskolin; IEA:Ensembl.
DR GO; GO:0097211; P:cellular response to gonadotropin-releasing hormone; IEA:Ensembl.
DR GO; GO:1990646; P:cellular response to prolactin; IEA:Ensembl.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0044597; P:daunorubicin metabolic process; IBA:GO_Central.
DR GO; GO:0044598; P:doxorubicin metabolic process; IBA:GO_Central.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007567; P:parturition; IMP:MGI.
DR GO; GO:0006709; P:progesterone catabolic process; IDA:MGI.
DR GO; GO:0042448; P:progesterone metabolic process; ISO:MGI.
DR GO; GO:0006693; P:prostaglandin metabolic process; IBA:GO_Central.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; ISO:MGI.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
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; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C18"
FT /id="PRO_0000124649"
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 VAR_SEQ 124..149
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014039"
SQ SEQUENCE 323 AA; 37177 MW; F2732C09C60B4544 CRC64;
MNSKIQKIEL NDGHSIPVLG FGTYATEEHL KKKSMESTKI AIDVGFCHID CSHLYQNEEE
IGQAILSKIE DGTVKREDIF YTSKLWSTSH RPELVRPSLE NSLRKLNLDY VDLYLIHFPV
SLKPGNELLP KDEHGNLIFD TVDLCDTWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNKP
GLKYKPVCNQ VECHLYLNQS KLLAYCKMND IVLVAYGALG TQRYKYCINE DTPVLLDDPV
LCAMAKKYKR TPALIALRYQ LDRGIVALAK SFNEERIREN MQVFDFQLAS DDMKILDGLD
RNLRYFPADM FKAHPNFPFF DEY
