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Database: UniProt
Entry: P52895
LinkDB: P52895
Original site: P52895 
ID   AK1C2_HUMAN             Reviewed;         323 AA.
AC   P52895; A8K2N9; B4DKR9; Q14133; Q5SR16; Q7M4N1; Q96A71;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2002, sequence version 3.
DT   09-JUL-2014, entry version 147.
DE   RecName: Full=Aldo-keto reductase family 1 member C2;
DE            EC=1.-.-.-;
DE   AltName: Full=3-alpha-HSD3;
DE   AltName: Full=Chlordecone reductase homolog HAKRD;
DE   AltName: Full=Dihydrodiol dehydrogenase 2;
DE            Short=DD-2;
DE            Short=DD2;
DE   AltName: Full=Dihydrodiol dehydrogenase/bile acid-binding protein;
DE            Short=DD/BABP;
DE   AltName: Full=Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase;
DE            EC=1.3.1.20;
DE   AltName: Full=Type III 3-alpha-hydroxysteroid dehydrogenase;
DE            EC=1.1.1.357;
GN   Name=AKR1C2; Synonyms=DDH2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=8274401; DOI=10.1016/0960-0760(93)90308-J;
RA   Qin K.-N., New M.I., Cheng K.-C.;
RT   "Molecular cloning of multiple cDNAs encoding human enzymes
RT   structurally related to 3 alpha-hydroxysteroid dehydrogenase.";
RL   J. Steroid Biochem. Mol. Biol. 46:673-679(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
RX   PubMed=8011662; DOI=10.1016/0005-2728(94)90144-9;
RA   Ciaccio P.J., Tew K.D.;
RT   "cDNA and deduced amino acid sequences of a human colon dihydrodiol
RT   dehydrogenase.";
RL   Biochim. Biophys. Acta 1186:129-132(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT TYR-46.
RX   PubMed=7959017; DOI=10.1016/0378-1119(94)90176-7;
RA   Qin K.-N., Khanna M., Cheng K.-C.;
RT   "Structure of a gene coding for human dihydrodiol dehydrogenase/bile
RT   acid-binding protein.";
RL   Gene 149:357-361(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC   TISSUE=Prostate;
RX   PubMed=8920937; DOI=10.1006/bbrc.1996.1684;
RA   Dufort I., Soucy P., Labrie F., Luu-The V.;
RT   "Molecular cloning of human type 3 3 alpha-hydroxysteroid
RT   dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase
RT   by seven amino acids.";
RL   Biochem. Biophys. Res. Commun. 228:474-479(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=9716498;
RA   Shiraishi H., Ishikura S., Matsuura K., Deyashiki Y., Ninomiya M.,
RA   Sakai S., Hara A.;
RT   "Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform
RT   (AKR1C2) and tissue distribution of its mRNA.";
RL   Biochem. J. 334:399-405(1998).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=10672042; DOI=10.1046/j.1365-2443.2000.00310.x;
RA   Nishizawa M., Nakajima T., Yasuda K., Kanzaki H., Sasaguri Y.,
RA   Watanabe K., Ito S.;
RT   "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with
RT   three aldo-keto reductase genes.";
RL   Genes Cells 5:111-125(2000).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA   Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA   Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA   Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA   Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA   Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA   Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA   Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA   Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA   Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA   Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA   Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA   Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA   Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA   Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA   Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA   Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung, and Urinary bladder;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   PROTEIN SEQUENCE OF 2-31; 40-62; 69-100; 105-131; 137-153; 162-206;
RP   209-231; 250-269 AND 271-323, FUNCTION, CATALYTIC ACTIVITY, ENZYME
RP   REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=8573067;
RA   Hara A., Matsuura K., Tamada Y., Sato K., Miyabe Y., Deyashiki Y.,
RA   Ishida N.;
RT   "Relationship of human liver dihydrodiol dehydrogenases to hepatic
RT   bile-acid-binding protein and an oxidoreductase of human colon
RT   cells.";
RL   Biochem. J. 313:373-376(1996).
RN   [12]
RP   PROTEIN SEQUENCE OF 10-29; 40-55; 76-101; 105-128; 137-146; 162-197;
RP   208-223; 259-270 AND 305-322.
RC   TISSUE=Liver;
RX   PubMed=8486699;
RA   Stolz A., Hammond L., Lou H., Takikawa H., Ronk M., Shively J.E.;
RT   "cDNA cloning and expression of the human hepatic bile acid-binding
RT   protein. A member of the monomeric reductase gene family.";
RL   J. Biol. Chem. 268:10448-10457(1993).
RN   [13]
RP   TISSUE SPECIFICITY, VARIANTS SRXY8 VAL-79; GLN-90; GLN-222 AND
RP   THR-300, AND CHARACTERIZATION OF VARIANTS SRXY8 VAL-79; GLN-90;
RP   GLN-222 AND THR-300.
RX   PubMed=21802064; DOI=10.1016/j.ajhg.2011.06.009;
RA   Fluck C.E., Meyer-Boni M., Pandey A.V., Kempna P., Miller W.L.,
RA   Schoenle E.J., Biason-Lauber A.;
RT   "Why boys will be boys: two pathways of fetal testicular androgen
RT   biosynthesis are needed for male sexual differentiation.";
RL   Am. J. Hum. Genet. 89:201-218(2011).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH NADP AND
RP   URSODEOXYCHOLATE.
RX   PubMed=11513593; DOI=10.1021/bi010919a;
RA   Jin Y., Stayrook S.E., Albert R.H., Palackal N.T., Penning T.M.,
RA   Lewis M.;
RT   "Crystal structure of human type III 3alpha-hydroxysteroid
RT   dehydrogenase/bile acid binding protein complexed with NADP(+) and
RT   ursodeoxycholate.";
RL   Biochemistry 40:10161-10168(2001).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH NADP AND
RP   TESTOSTERONE.
RX   PubMed=11514561; DOI=10.1074/jbc.M105610200;
RA   Nahoum V., Gangloff A., Legrand P., Zhu D.-W., Cantin L., Zhorov B.S.,
RA   Luu-The V., Labrie F., Breton R., Lin S.X.;
RT   "Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in
RT   complex with testosterone and NADP at 1.25-A resolution.";
RL   J. Biol. Chem. 276:42091-42098(2001).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-323 IN COMPLEX WITH NADP,
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-301 AND ARG-304.
RX   PubMed=15929998; DOI=10.1110/ps.051353205;
RA   Couture J.F., de Jesus-Tran K.P., Roy A.M., Cantin L., Cote P.L.,
RA   Legrand P., Luu-The V., Labrie F., Breton R.;
RT   "Comparison of crystal structures of human type 3 3alpha-
RT   hydroxysteroid dehydrogenase reveals an 'induced-fit' mechanism and a
RT   conserved basic motif involved in the binding of androgen.";
RL   Protein Sci. 14:1485-1497(2005).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION,
RP   AND CATALYTIC ACTIVITY.
RX   PubMed=17034817; DOI=10.1016/j.jmb.2006.09.030;
RA   Faucher F., Pereira de Jesus-Tran K., Cantin L., Luu-The V.,
RA   Labrie F., Breton R.;
RT   "Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase
RT   (apoenzyme and enzyme-NADP(H) binary complex): identification of
RT   molecular determinants responsible for the unique 17alpha-reductive
RT   activity of this enzyme.";
RL   J. Mol. Biol. 364:747-763(2006).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 3-323 IN COMPLEX WITH NADP
RP   AND HYDROXYANDROSTERONE, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS
RP   OF TYR-24 AND LYS-31.
RX   PubMed=17442338; DOI=10.1016/j.jmb.2007.03.058;
RA   Faucher F., Cantin L., Pereira de Jesus-Tran K., Lemieux M.,
RA   Luu-The V., Labrie F., Breton R.;
RT   "Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids
RT   differently from other aldo-keto reductases: identification and
RT   characterization of amino acid residues critical for substrate
RT   binding.";
RL   J. Mol. Biol. 369:525-540(2007).
CC   -!- FUNCTION: Works in concert with the 5-alpha/5-beta-steroid
CC       reductases to convert steroid hormones into the 3-alpha/5-alpha
CC       and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation
CC       of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-
CC       DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol).
CC       Has a high bile-binding ability.
CC   -!- CATALYTIC ACTIVITY: Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) =
CC       catechol + NADPH.
CC   -!- CATALYTIC ACTIVITY: A 3-alpha-hydroxysteroid + NAD(P)(+) = a 3-
CC       oxosteroid + NAD(P)H.
CC   -!- ENZYME REGULATION: Inhibited by hexestrol with an IC(50) of 2.8
CC       uM, 1,10-phenanthroline with an IC(50) of 2100 uM, 1,7-
CC       phenanthroline with an IC(50) of 1500 uM, flufenamic acid with an
CC       IC(50) of 0.9 uM, indomethacin with an IC(50) of 75 uM, ibuprofen
CC       with an IC(50) of 6.9 uM, lithocholic acid with an IC(50) of 0.07
CC       uM, ursodeoxycholic acid with an IC(50) of 0.08 uM and
CC       chenodeoxycholic acid with an IC(50) of 0.13 uM.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=260 uM for (s)-tetralol;
CC         KM=520 uM for (s)-indan-1-ol;
CC         KM=5000 uM for benzene dihydrodiol;
CC         KM=1 uM for 5-beta-pregnane-3-alpha,20-alpha-diol;
CC         KM=208 uM for 9-alpha,11-beta-PGF2;
CC         KM=0.3 uM for 5-beta-androstane-3,17-dione;
CC         KM=79 uM for PGD2;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P52895-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P52895-2; Sequence=VSP_043779, VSP_043780;
CC         Note=No experimental confirmation available;
CC   -!- TISSUE SPECIFICITY: Expressed in fetal testes. Expressed in fetal
CC       and adult adrenal glands.
CC   -!- DISEASE: 46,XY sex reversal 8 (SRXY8) [MIM:614279]: A disorder of
CC       sex development. Affected individuals have a 46,XY karyotype but
CC       present as phenotypically normal females. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family.
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DR   EMBL; S68330; AAD14013.1; -; mRNA.
DR   EMBL; U05598; AAA20937.1; -; mRNA.
DR   EMBL; L32592; AAB38486.1; -; Genomic_DNA.
DR   EMBL; AB021654; BAA36169.1; -; mRNA.
DR   EMBL; AB031084; BAA92884.1; -; mRNA.
DR   EMBL; AB032153; BAA92891.1; -; Genomic_DNA.
DR   EMBL; AK290304; BAF82993.1; -; mRNA.
DR   EMBL; AK296686; BAG59281.1; -; mRNA.
DR   EMBL; BT006653; AAP35299.1; -; mRNA.
DR   EMBL; AL713867; CAI16408.1; -; Genomic_DNA.
DR   EMBL; AL391427; CAI16408.1; JOINED; Genomic_DNA.
DR   EMBL; BC007024; AAH07024.1; -; mRNA.
DR   EMBL; BC063574; AAH63574.1; -; mRNA.
DR   CCDS; CCDS44350.1; -. [P52895-2]
DR   CCDS; CCDS7062.1; -. [P52895-1]
DR   PIR; I73676; I73676.
DR   PIR; JC5240; JC5240.
DR   PIR; S61516; S61516.
DR   RefSeq; NP_001128713.1; NM_001135241.2. [P52895-2]
DR   RefSeq; NP_001345.1; NM_001354.5. [P52895-1]
DR   RefSeq; NP_995317.1; NM_205845.2. [P52895-1]
DR   UniGene; Hs.460260; -.
DR   UniGene; Hs.567256; -.
DR   UniGene; Hs.734597; -.
DR   PDB; 1IHI; X-ray; 3.00 A; A/B=1-323.
DR   PDB; 1J96; X-ray; 1.25 A; A/B=2-323.
DR   PDB; 1XJB; X-ray; 1.90 A; A/B=2-323.
DR   PDB; 2HDJ; X-ray; 2.00 A; A/B=1-323.
DR   PDB; 2IPJ; X-ray; 1.80 A; A/B=3-323.
DR   PDB; 4JQ1; X-ray; 1.60 A; A/B=1-323.
DR   PDB; 4JQ2; X-ray; 1.75 A; A/B=1-323.
DR   PDB; 4JQ3; X-ray; 1.75 A; A/B=1-323.
DR   PDB; 4JQ4; X-ray; 1.52 A; A/B=1-323.
DR   PDB; 4JQA; X-ray; 1.45 A; A/B=1-323.
DR   PDB; 4JTQ; X-ray; 1.60 A; A/B=1-323.
DR   PDB; 4JTR; X-ray; 1.30 A; A/B=1-323.
DR   PDB; 4L1W; X-ray; 2.20 A; A/B=2-323.
DR   PDB; 4L1X; X-ray; 2.00 A; A/B=2-323.
DR   PDBsum; 1IHI; -.
DR   PDBsum; 1J96; -.
DR   PDBsum; 1XJB; -.
DR   PDBsum; 2HDJ; -.
DR   PDBsum; 2IPJ; -.
DR   PDBsum; 4JQ1; -.
DR   PDBsum; 4JQ2; -.
DR   PDBsum; 4JQ3; -.
DR   PDBsum; 4JQ4; -.
DR   PDBsum; 4JQA; -.
DR   PDBsum; 4JTQ; -.
DR   PDBsum; 4JTR; -.
DR   PDBsum; 4L1W; -.
DR   PDBsum; 4L1X; -.
DR   ProteinModelPortal; P52895; -.
DR   SMR; P52895; 2-323.
DR   BioGrid; 108013; 1.
DR   IntAct; P52895; 1.
DR   STRING; 9606.ENSP00000370129; -.
DR   BindingDB; P52895; -.
DR   ChEMBL; CHEMBL5847; -.
DR   DrugBank; DB00157; NADH.
DR   DrugBank; DB01586; Ursodeoxycholic acid.
DR   PhosphoSite; P52895; -.
DR   DMDM; 20532374; -.
DR   MaxQB; P52895; -.
DR   PaxDb; P52895; -.
DR   PRIDE; P52895; -.
DR   DNASU; 1646; -.
DR   Ensembl; ENST00000380753; ENSP00000370129; ENSG00000151632. [P52895-1]
DR   Ensembl; ENST00000407674; ENSP00000385221; ENSG00000151632. [P52895-1]
DR   Ensembl; ENST00000455190; ENSP00000408440; ENSG00000151632. [P52895-2]
DR   Ensembl; ENST00000580545; ENSP00000464045; ENSG00000265231. [P52895-1]
DR   GeneID; 1646; -.
DR   KEGG; hsa:101930400; -.
DR   KEGG; hsa:1646; -.
DR   UCSC; uc001ihs.3; human. [P52895-1]
DR   UCSC; uc010qao.2; human. [P52895-2]
DR   CTD; 1646; -.
DR   GeneCards; GC10M005021; -.
DR   HGNC; HGNC:385; AKR1C2.
DR   HPA; CAB047304; -.
DR   MIM; 600450; gene.
DR   MIM; 614279; phenotype.
DR   neXtProt; NX_P52895; -.
DR   Orphanet; 90796; 46,XY disorder of sex development due to isolated 17, 20 lyase deficiency.
DR   PharmGKB; PA24678; -.
DR   eggNOG; COG0656; -.
DR   HOGENOM; HOG000250272; -.
DR   HOVERGEN; HBG000020; -.
DR   InParanoid; P52895; -.
DR   KO; K00089; -.
DR   KO; K00212; -.
DR   OMA; YTSKLWI; -.
DR   PhylomeDB; P52895; -.
DR   TreeFam; TF106492; -.
DR   BioCyc; MetaCyc:HS07754-MONOMER; -.
DR   BRENDA; 1.1.1.213; 2681.
DR   Reactome; REACT_111217; Metabolism.
DR   SABIO-RK; P52895; -.
DR   SignaLink; P52895; -.
DR   EvolutionaryTrace; P52895; -.
DR   NextBio; 6772; -.
DR   PRO; PR:P52895; -.
DR   ArrayExpress; P52895; -.
DR   Bgee; P52895; -.
DR   CleanEx; HS_AKR1C2; -.
DR   Genevestigator; P52895; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:UniProtKB.
DR   GO; GO:0032052; F:bile acid binding; IDA:UniProtKB.
DR   GO; GO:0031406; F:carboxylic acid binding; IDA:UniProtKB.
DR   GO; GO:0047086; F:ketosteroid monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR   GO; GO:0018636; F:phenanthrene 9,10-monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0004958; F:prostaglandin F receptor activity; IDA:UniProtKB.
DR   GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0071395; P:cellular response to jasmonic acid stimulus; IDA:UniProtKB.
DR   GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB.
DR   GO; GO:0007586; P:digestion; IDA:UniProtKB.
DR   GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB.
DR   GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProt.
DR   GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0055114; P:oxidation-reduction process; IDA:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR   GO; GO:0042448; P:progesterone metabolic process; IDA:UniProtKB.
DR   GO; GO:0006693; P:prostaglandin metabolic process; IDA:UniProtKB.
DR   GO; GO:0034694; P:response to prostaglandin; IDA:UniProtKB.
DR   GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR   Gene3D; 3.20.20.100; -; 1.
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   PANTHER; PTHR11732; PTHR11732; 1.
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   3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW   Direct protein sequencing; Disease mutation; Lipid metabolism; NADP;
KW   Oxidoreductase; Polymorphism; Reference proteome; Steroid metabolism.
FT   CHAIN         1    323       Aldo-keto reductase family 1 member C2.
FT                                /FTId=PRO_0000124637.
FT   NP_BIND      20     24       NADP.
FT   NP_BIND     166    167       NADP.
FT   NP_BIND     216    222       NADP.
FT   NP_BIND     270    280       NADP.
FT   ACT_SITE     55     55       Proton donor.
FT   BINDING      24     24       Substrate (By similarity).
FT   BINDING      50     50       NADP.
FT   BINDING     117    117       Substrate.
FT   BINDING     190    190       NADP.
FT   BINDING     222    222       Substrate (By similarity).
FT   BINDING     227    227       Substrate.
FT   SITE         84     84       Lowers pKa of active site Tyr (By
FT                                similarity).
FT   VAR_SEQ     124    139       PGEEVIPKDENGKILF -> EDIGILTWKKSPKHNS (in
FT                                isoform 2).
FT                                /FTId=VSP_043779.
FT   VAR_SEQ     140    323       Missing (in isoform 2).
FT                                /FTId=VSP_043780.
FT   VARIANT      46     46       F -> Y (in dbSNP:rs2854482).
FT                                /FTId=VAR_048216.
FT   VARIANT      79     79       I -> V (in SRXY8; partially impaired
FT                                activity).
FT                                /FTId=VAR_066632.
FT   VARIANT      90     90       H -> Q (in SRXY8; partially impaired
FT                                activity).
FT                                /FTId=VAR_066633.
FT   VARIANT     172    172       L -> Q (in dbSNP:rs11474).
FT                                /FTId=VAR_014748.
FT   VARIANT     222    222       H -> Q (in SRXY8; partially impaired
FT                                activity).
FT                                /FTId=VAR_066634.
FT   VARIANT     300    300       N -> T (in SRXY8; partially impaired
FT                                activity).
FT                                /FTId=VAR_066635.
FT   MUTAGEN      24     24       Y->A: Strongly decreases affinity for
FT                                androstenedione. Decreases
FT                                androstenedione reductase activity about
FT                                60-fold.
FT   MUTAGEN      31     31       K->A,M: Increases the low androstenedione
FT                                reductase activity.
FT   MUTAGEN     301    301       R->A: Decreases 3-alpha-hydroxysteroid
FT                                reductase activity about 50-fold.
FT   MUTAGEN     304    304       R->A: Decreases 3-alpha-hydroxysteroid
FT                                reductase activity about 500-fold.
FT   CONFLICT     76     76       R -> S (in Ref. 12; AA sequence).
FT   CONFLICT     87     87       S -> C (in Ref. 12; AA sequence).
FT   CONFLICT     93     93       E -> EE (in Ref. 12; AA sequence).
FT   CONFLICT    111    111       V -> A (in Ref. 3; AAB38486).
FT   CONFLICT    164    164       G -> R (in Ref. 7; BAF82993).
FT   CONFLICT    179    179       K -> E (in Ref. 1; AAD14013 and 3;
FT                                AAB38486).
FT   CONFLICT    185    185       K -> E (in Ref. 1; AAD14013 and 3;
FT                                AAB38486).
FT   CONFLICT    188    188       C -> H (in Ref. 12; AA sequence).
FT   CONFLICT    193    193       C -> H (in Ref. 12; AA sequence).
FT   CONFLICT    319    319       F -> I (in Ref. 1; AAD14013 and 3;
FT                                AAB38486).
FT   STRAND        7      9
FT   STRAND       15     22
FT   HELIX        32     44
FT   STRAND       48     50
FT   HELIX        53     55
FT   HELIX        58     70
FT   HELIX        76     78
FT   STRAND       80     85
FT   HELIX        87     89
FT   HELIX        92     94
FT   HELIX        95    106
FT   STRAND      111    116
FT   STRAND      119    122
FT   STRAND      124    126
FT   HELIX       144    156
FT   STRAND      159    167
FT   HELIX       170    177
FT   STRAND      187    192
FT   HELIX       200    208
FT   STRAND      212    217
FT   TURN        225    227
FT   HELIX       235    237
FT   HELIX       239    248
FT   HELIX       252    262
FT   STRAND      266    270
FT   HELIX       274    280
FT   HELIX       281    285
FT   HELIX       290    297
FT   HELIX       309    311
FT   STRAND      318    321
SQ   SEQUENCE   323 AA;  36735 MW;  0D7B6F983FCE85E1 CRC64;
     MDSKYQCVKL NDGHFMPVLG FGTYAPAEVP KSKALEAVKL AIEAGFHHID SAHVYNNEEQ
     VGLAIRSKIA DGSVKREDIF YTSKLWSNSH RPELVRPALE RSLKNLQLDY VDLYLIHFPV
     SVKPGEEVIP KDENGKILFD TVDLCATWEA MEKCKDAGLA KSIGVSNFNH RLLEMILNKP
     GLKYKPVCNQ VECHPYFNQR KLLDFCKSKD IVLVAYSALG SHREEPWVDP NSPVLLEDPV
     LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTS EEMKAIDGLN
     RNVRYLTLDI FAGPPNYPFS DEY
//
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