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ID HS10_PE101 STANDARD; PRT; 323 AA.
AC HS10_PE101; P17516; Q5T6A3; Q8WW84; Q9NS54;
DT 00-JAN-0000 (Rel. 1, Created)
DT 00-JAN-0000 (Rel. 2, Last sequence update)
DT 00-JAN-0000 (Rel. 3, Last annotation update)
DE RecName: Full=Aldo-keto reductase family 1 member C4; EC=1.1.1.-;AltName:
DE Full=3-alpha-HSD1;AltName: Full=3-alpha-hydroxysteroid dehydrogenase type
DE I; EC=1.1.1.50;AltName: Full=Chlordecone reductase; Short=CDR; EC=1.1.1
DE 225;AltName: Full=Dihydrodiol dehydrogenase 4; Short=DD-4;
DE Short=DD4;AltName: Full=HAKRA; (HS10.PE101).
GN Name=AKR1C4; Synonyms=CHDR;
OS HOMO SAPIENS.
OC Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC Hominoidea; Hominidae; Homininae; Homo.
OX NCBI_TaxID=9606;
RN [0]
RP -.;
RG -.;
RL -.;
CC -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS10.PE101.
CC Homo sapiens chromosome 10 GRCh37 sequence 1..135524747 annotated by
CC Ensembl
CC -!- ANNOTATIONS ORIGIN:AK1C4_HUMAN
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.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Liver specific.
CC -!- PTM: The N-terminus is blocked.
CC -!- POLYMORPHISM: The allele with Cys-145/Val-311 shows a three- to
CC five-fold decrease in catalytic efficiency for xenobiotic and
CC steroidal substrates compared to the Ser-145/Leu-311 allele.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35658.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- GENE_FAMILY: HOG000250272 [ FAMILY / ALN / TREE ]
DR HOGENOM:Homo_sapiens;ENSG00000198610;ENST00000263126;ENSP00000263126.
DR EMBL; AB031085; - ;
DR EMBL; AB032163; - ;
DR EMBL; AB045829; - ;
DR EMBL; AL355303; - ;
DR EMBL; BC020744; - ;
DR EMBL; D26125; - ;
DR EMBL; D89962; - ;
DR EMBL; M33375; - ;
DR EMBL; S68287; - ;
DR UniProtKB/Swiss-Prot; P17516; Q5T6A3; Q8WW84; Q9NS54; -.
DR EMBL; S68287; AAD14010.1; -; mRNA.
DR EMBL; AB045829; BAA99542.1; -; mRNA.
DR EMBL; AB031085; BAA92885.1; -; mRNA.
DR EMBL; AB032163; BAA92893.1; -; Genomic_DNA.
DR EMBL; AL355303; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020744; AAH20744.1; -; mRNA.
DR EMBL; M33375; AAA35658.1; ALT_INIT; mRNA.
DR EMBL; D26125; BAA05122.1; -; mRNA.
DR IPI; IPI00289524; -.
DR PIR; A57407; A57407.
DR PIR; S59620; S59620.
DR RefSeq; NP_001809.3; NM_001818.3.
DR UniGene; Hs.567245; -.
DR PDB; 2FVL; X-ray; 2.40 A; A/B/C=1-323.
DR PDBsum; 2FVL; -.
DR ProteinModelPortal; P17516; -.
DR SMR; P17516; 1-323.
DR STRING; P17516; -.
DR PhosphoSite; P17516; -.
DR PRIDE; P17516; -.
DR Ensembl; ENST00000263126; ENSP00000263126; ENSG00000198610.
DR Ensembl; ENST00000380448; ENSP00000369814; ENSG00000198610.
DR GeneID; 1109; -.
DR KEGG; hsa:1109; -.
DR UCSC; uc001ihw.1; human.
DR CTD; 1109; -.
DR GeneCards; GC10P005228; -.
DR H-InvDB; HIX0008607; -.
DR HGNC; HGNC:387; AKR1C4.
DR HPA; CAB006258; -.
DR MIM; 600451; gene.
DR neXtProt; NX_P17516; -.
DR PharmGKB; PA24680; -.
DR eggNOG; prNOG19511; -.
DR InParanoid; P17516; -.
DR OMA; KYQRVEL; -.
DR OrthoDB; EOG4Q2DG2; -.
DR PhylomeDB; P17516; -.
DR Reactome; REACT_22258; Metabolism of lipids and lipoproteins.
DR DrugBank; DB00157; NADH.
DR NextBio; 4602; -.
DR ArrayExpress; P17516; -.
DR Bgee; P17516; -.
DR CleanEx; HS_AKR1C4; -.
DR Genevestigator; P17516; -.
DR GermOnline; ENSG00000198610; Homo sapiens.
DR GO; GO:0005829; C:cytosol; EXP:Reactome.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; EXP:Reactome.
DR GO; GO:0047042; F:androsterone dehydrogenase (B-specific) activity; IEA:EC.
DR GO; GO:0015125; F:bile acid transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0047743; F:chlordecone reductase activity; IEA:EC.
DR GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; TAS:ProtInc.
DR GO; GO:0006699; P:bile acid biosynthetic process; TAS:Reactome.
DR InterPro; IPR001395; Aldo/ket_red.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR020471; Aldo/keto_reductase_subgr.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
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 PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; 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.
DR HOGENOMDNA; HS10.PE101; -.
KW ENSG000001986101755old_1320000031; ENSP000002631267901old_1320000031;
KW Q96SD9_HUMAN; AB031085; AB032163; AB045829; AL355303; BC020744; D26125;
KW M33375; S68287;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NADP; Oxidoreductase; Phosphoprotein;
KW Polymorphism; Reference proteome.
SQ SEQUENCE 323 AA; UNKNOWN MW; UNKNOWN CRC64;
MDPKYQRVEL NDGHFMPVLG FGTYAPPEVP RNRAVEVTKL AIEAGFRHID SAYLYNNEEQ
VGLAIRSKIA DGSVKREDIF YTSKLWCTFF QPQMVQPALE SSLKKLQLDY VDLYLLHFPM
ALKPGETPLP KDENGKVIFD TVDLSATWEV MEKCKDAGLA KSIGVSNFNC RQLEMILNKP
GLKYKPVCNQ VECHPYLNQS KLLDFCKSKD IVLVAHSALG TQRHKLWVDP NSPVLLEDPV
LCALAKKHKQ TPALIALRYQ LQRGVVVLAK SYNEQRIREN IQVFEFQLTS EDMKVLDGLN
RNYRYVVMDF LMDHPDYPFS DEY
//
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