ID   AK1C4_MACFA             Reviewed;         323 AA.
AC   Q95JH5;
DT   07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   16-JUN-2009, entry version 40.
DE   RecName: Full=Aldo-keto reductase family 1 member C4;
DE            EC=1.1.1.-;
DE   AltName: Full=Chlordecone reductase;
DE            Short=CDR;
DE            EC=1.1.1.225;
DE   AltName: Full=3-alpha-hydroxysteroid dehydrogenase type I;
DE            EC=1.1.1.50;
DE   AltName: Full=3-alpha-HSD1;
DE   AltName: Full=Dihydrodiol dehydrogenase 4;
DE            Short=DD-4;
DE            Short=DD4;
GN   Name=AKR1C4;
OS   Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-23; 69-116;
RP   137-153; 184-246 AND 250-323.
RC   TISSUE=Liver;
RX   PubMed=15618685; DOI=10.2133/dmpk.17.348;
RA   Higaki Y., Kamiya T., Usami N., Shintani S., Shiraishi H.,
RA   Ishikura S., Yamamoto I., Hara A.;
RT   "Molecular characterization of two monkey dihydrodiol
RT   dehydrogenases.";
RL   Drug Metab. Pharmacokinet. 17:348-356(2002).
CC   -!- FUNCTION: Catalyzes the transformation of the potent androgen
CC       dihydrotestosterone (DHT) into the less active form, 5-alpha-
CC       androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-
CC       alpha-hydroxysteroid dehydrogenase activity. The biotransformation
CC       of the pesticide chlordecone (kepone) to its corresponding alcohol
CC       leads to increased biliary excretion of the pesticide and
CC       concomitant reduction of its neurotoxicity since bile is the major
CC       excretory route.
CC   -!- CATALYTIC ACTIVITY: Chlordecone alcohol + NADP(+) = chlordecone +
CC       NADPH.
CC   -!- CATALYTIC ACTIVITY: Androsterone + NAD(P)(+) = 5-alpha-androstane-
CC       3,17-dione + NAD(P)H.
CC   -!- SUBUNIT: Monomer (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family.
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DR   EMBL; AB070211; BAB63208.1; -; mRNA.
DR   HSSP; Q04828; 1MRQ.
DR   SMR; Q95JH5; 1-323.
DR   HOVERGEN; Q95JH5; -.
DR   BRENDA; 1.1.1.225; 3438.
DR   BRENDA; 1.1.1.50; 3438.
DR   BRENDA; 1.3.1.20; 3438.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0047042; F:3-alpha-hydroxysteroid dehydrogenase (B-spe...; IEA:EC.
DR   GO; GO:0047743; F:chlordecone reductase activity; IEA:EC.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   InterPro; IPR001395; Aldo/ket_red.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   Gene3D; G3DSA:3.20.20.100; Aldo/ket_red; 1.
DR   PANTHER; PTHR11732; Aldo/ket_red; 1.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   ProDom; PD000288; Aldo/ket_red; 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   Phosphoprotein.
FT   CHAIN         1    323       Aldo-keto reductase family 1 member C4.
FT                                /FTId=PRO_0000124641.
FT   NP_BIND      13     22       NADP (Potential).
FT   NP_BIND     217    280       NADP (By similarity).
FT   ACT_SITE     55     55       Proton donor (By similarity).
FT   BINDING     117    117       Substrate (By similarity).
FT   SITE         54     54       Important for substrate specificity (By
FT                                similarity).
FT   SITE         84     84       Lowers pKa of active site Tyr (By
FT                                similarity).
FT   MOD_RES     196    196       Phosphotyrosine (By similarity).
SQ   SEQUENCE   323 AA;  37117 MW;  3E7F2E78815AA196 CRC64;
     MDPKYQRVAL NDGHFMPVLG FGTYAPPEVP RNRVVEVTKL AIEAGFRHID SAYLYNNEEQ
     VGLAIRSKIA DGSVKREDIF YTSKLWCTFF RPQLVQPALE SSLKKLQLDY VDLYLIHFPM
     ALKPGETPLP KDENGKVMFD TVDLCAIWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNNP
     GLKYKPVCNQ VECHPYLNQS KLLDFCKSKD IVLVAHSALG TQRHKLWVDQ NSPALLEDPV
     LCALAKKHKR SPALIALRYQ LQRGVVVLAK SYNEQRIREN VQVFEFQLTS EDMKVLDDLN
     RNFRYVVMDF LVDHPDYPFS DEY
//