AK1CL_RAT
ID AK1CL_RAT Reviewed; 318 AA.
AC Q6AYQ2;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Aldo-keto reductase family 1 member C21;
DE EC=1.1.1.-;
DE AltName: Full=17-alpha-hydroxysteroid dehydrogenase;
DE Short=17-alpha-HSD;
DE AltName: Full=3(or 17)-alpha-hydroxysteroid dehydrogenase;
DE EC=1.1.1.209;
DE AltName: Full=3-alpha-hydroxysteroid dehydrogenase;
GN Name=Akr1c21;
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 [LARGE SCALE MRNA].
RC 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).
CC -!- FUNCTION: NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that
CC converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-
CC alpha-hydroxysteroid dehydrogenase activity. Has broad substrate
CC specificity and acts on various 17-alpha-hydroxysteroids, 17-
CC ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of
CC keto groups is strictly stereoselective. Reduction of 17-ketosteroids
CC yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-
CC ketosteroids yields only 3-alpha-hydroxysteroids (By similarity).
CC {ECO:0000250}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:20381,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.209;
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; BC078957; AAH78957.1; -; mRNA.
DR RefSeq; NP_001013075.1; NM_001013057.1.
DR AlphaFoldDB; Q6AYQ2; -.
DR SMR; Q6AYQ2; -.
DR STRING; 10116.ENSRNOP00000045355; -.
DR iPTMnet; Q6AYQ2; -.
DR PhosphoSitePlus; Q6AYQ2; -.
DR jPOST; Q6AYQ2; -.
DR PaxDb; Q6AYQ2; -.
DR GeneID; 291283; -.
DR KEGG; rno:291283; -.
DR UCSC; RGD:1311841; rat.
DR CTD; 1646; -.
DR RGD; 1311841; Akr1c21.
DR VEuPathDB; HostDB:ENSRNOG00000029844; -.
DR eggNOG; KOG1577; Eukaryota.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; Q6AYQ2; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; Q6AYQ2; -.
DR TreeFam; TF106492; -.
DR PRO; PR:Q6AYQ2; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000029844; Expressed in liver and 4 other tissues.
DR ExpressionAtlas; Q6AYQ2; baseline.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) activity; ISO:RGD.
DR GO; GO:0072555; F:17-beta-ketosteroid reductase activity; ISO:RGD.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; ISO:RGD.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; ISO:RGD.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; ISO:RGD.
DR GO; GO:0032052; F:bile acid binding; ISO:RGD.
DR GO; GO:0031406; F:carboxylic acid binding; ISO:RGD.
DR GO; GO:0047086; F:ketosteroid monooxygenase activity; ISO:RGD.
DR GO; GO:1902121; F:lithocholic acid binding; ISO:RGD.
DR GO; GO:0070401; F:NADP+ binding; ISO:RGD.
DR GO; GO:0070402; F:NADPH binding; 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:0005496; F:steroid binding; ISO:RGD.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0033764; F:steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; ISO:RGD.
DR GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; ISO:RGD.
DR GO; GO:0071395; P:cellular response to jasmonic acid stimulus; ISO:RGD.
DR GO; GO:0071799; P:cellular response to prostaglandin D stimulus; ISO:RGD.
DR GO; GO:0044597; P:daunorubicin metabolic process; ISO:RGD.
DR GO; GO:0007586; P:digestion; ISO:RGD.
DR GO; GO:0044598; P:doxorubicin metabolic process; ISO:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0042448; P:progesterone metabolic process; ISO:RGD.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD.
DR GO; GO:0008202; P:steroid metabolic 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; PS00062; ALDOKETO_REDUCTASE_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Lipid metabolism; NADP; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..318
FT /note="Aldo-keto reductase family 1 member C21"
FT /id="PRO_0000326223"
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 31
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..224
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 84
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
SQ SEQUENCE 318 AA; 36135 MW; 53909644919456D1 CRC64;
MNSKCHCVKL NDGHFIPVLG FGTAMPSELP KSKAKEVTKI AIDAGFHHFD SAFVYNTEDH
VGEAIREKIA NGTTRREDIF YTSKLWCTSL HPELVRSSLE CSLKKLQLDY VDLYLIHFPM
ALKPGDENFP VDEHGKLLFD TVDLCATWEA MEKCKDAGLA KSIGVSNFNR RQLEKILNKP
GLKYKPVCNQ VECHLYLNQM KLLDFCKTNG IILVAYGVLG TQRYNGWVDQ NSPVLLNEPV
LSSMAKKYNQ TPALIALRHQ LQRGIVVLNT SLKEERIKEN MKLSPEDMKV LDDLNRNLRY
IAGGIFEGHP NFPFLDEY
