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UniProtKB/Swiss-Prot entry P52895


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name AK1C2_HUMAN
Primary accession number P52895
Secondary accession numbers A8K2N9 Q14133 Q5SR16 Q7M4N1 Q96A71
Integrated into Swiss-Prot on October 1, 1996
Sequence was last modified on May 10, 2002 (Sequence version 3)
Annotations were last modified on    November 4, 2008 (Entry version 84)
Name and origin of the protein
Protein name Aldo-keto reductase family 1 member C2
Synonyms EC 1.-.-.-
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
EC 1.3.1.20
Type III 3-alpha-hydroxysteroid dehydrogenase
EC 1.1.1.213
3-alpha-HSD3
Dihydrodiol dehydrogenase 2
DD-2
DD2
Dihydrodiol dehydrogenase/bile acid-binding protein
DD/BABP
Chlordecone reductase homolog HAKRD
Gene name
Name: AKR1C2
Synonyms: DDH2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
DOI=10.1016/0960-0760(93)90308-J; PubMed=8274401 [NCBI, ExPASy, EBI, Israel, Japan]
Qin K.-N., New M.I., Cheng K.-C.;
"Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase.";
J. Steroid Biochem. Mol. Biol. 46:673-679(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Colon;
DOI=10.1016/0005-2728(94)90144-9; PubMed=8011662 [NCBI, ExPASy, EBI, Israel, Japan]
Ciaccio P.J., Tew K.D.;
"cDNA and deduced amino acid sequences of a human colon dihydrodiol dehydrogenase.";
Biochim. Biophys. Acta 1186:129-132(1994).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1016/0378-1119(94)90176-7; PubMed=7959017 [NCBI, ExPASy, EBI, Israel, Japan]
Qin K.-N., Khanna M., Cheng K.-C.;
"Structure of a gene coding for human dihydrodiol dehydrogenase/bile acid-binding protein.";
Gene 149:357-361(1994).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Prostate;
DOI=10.1006/bbrc.1996.1684; PubMed=8920937 [NCBI, ExPASy, EBI, Israel, Japan]
Dufort I., Soucy P., Labrie F., Luu-The V.;
"Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino acids.";
Biochem. Biophys. Res. Commun. 228:474-479(1996).
[5]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
PubMed=9716498 [NCBI, ExPASy, EBI, Israel, Japan]
Shiraishi H., Ishikura S., Matsuura K., Deyashiki Y., Ninomiya M., Sakai S., Hara A.;
"Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.";
Biochem. J. 334:399-405(1998).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
TISSUE=Liver;
DOI=10.1046/j.1365-2443.2000.00310.x; PubMed=10672042 [NCBI, ExPASy, EBI, Israel, Japan]
Nishizawa M., Nakajima T., Yasuda K., Kanzaki H., Sasaguri Y., Watanabe K., Ito S.;
"Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes.";
Genes Cells 5:111-125(2000).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Tongue;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02462; PubMed=15164054 [NCBI, ExPASy, EBI, Israel, Japan]
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung, and Urinary bladder;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[11]
PROTEIN SEQUENCE OF 2-31; 40-62; 69-100; 105-131; 137-153; 162-206; 209-231; 250-269 AND 271-323, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=8573067 [NCBI, ExPASy, EBI, Israel, Japan]
Hara A., Matsuura K., Tamada Y., Sato K., Miyabe Y., Deyashiki Y., Ishida N.;
"Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells.";
Biochem. J. 313:373-376(1996).
[12]
PROTEIN SEQUENCE OF 10-29; 40-55; 76-101; 105-128; 137-146; 162-197; 208-223; 259-270 AND 305-322.
TISSUE=Liver;
PubMed=8486699 [NCBI, ExPASy, EBI, Israel, Japan]
Stolz A., Hammond L., Lou H., Takikawa H., Ronk M., Shively J.E.;
"cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family.";
J. Biol. Chem. 268:10448-10457(1993).
[13]
X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH NADP AND URSODEOXYCHOLATE.
DOI=10.1021/bi010919a; PubMed=11513593 [NCBI, ExPASy, EBI, Israel, Japan]
Jin Y., Stayrook S.E., Albert R.H., Palackal N.T., Penning T.M., Lewis M.;
"Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate.";
Biochemistry 40:10161-10168(2001).
[14]
X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH NADP AND TESTOSTERONE.
DOI=10.1074/jbc.M105610200; PubMed=11514561 [NCBI, ExPASy, EBI, Israel, Japan]
Nahoum V., Gangloff A., Legrand P., Zhu D.-W., Cantin L., Zhorov B.S., Luu-The V., Labrie F., Breton R., Lin S.X.;
"Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution.";
J. Biol. Chem. 276:42091-42098(2001).
Comments
  • FUNCTION: Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.
  • CATALYTIC ACTIVITY: Trans-1,2-dihydrobenzene-1,2-diol + NADP+ = catechol + NADPH.
  • CATALYTIC ACTIVITY: Androsterone + NAD(P)+ = 5-alpha-androstane-3,17-dione + NAD(P)H.
  • ENZYME REGULATION: Inhibited by hexestrol with an IC50 of 2.8 µM, 1,10-phenanthroline with an IC50 of 2100 µM, 1,7-phenanthroline with an IC50 of 1500 µM, flufenamic acid with an IC50 of 0.9 µM, indomethacin with an IC50 of 75 µM, ibuprofen with an IC50 of 6.9 µM, lithocholic acid with an IC50 of 0.07 µM, ursodeoxycholic acid with an IC50 of 0.08 µM and chenodeoxycholic acid with an IC50 of 0.13 µM.
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=260 µM for (s)-tetralol;
    KM=520 µM for (s)-indan-1-ol;
    KM=5000 µM for benzene dihydrodiol;
    KM=1 µM for 5-beta-pregnane-3-alpha,20-alpha-diol;
    KM=208 µM for 9-alpha,11-beta-PGF2;
    KM=0.3 µM for 5-beta-androstane-3,17-dione;
    KM=79 µM for PGD2;
  • SUBCELLULAR LOCATION: Cytoplasm (Potential).
  • SIMILARITY: Belongs to the aldo/keto reductase family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
S68330; AAD14013.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U05598; AAA20937.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L32592; AAB38486.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB021654; BAA36169.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB031084; BAA92884.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB032153; BAA92891.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK290304; BAF82993.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT006653; AAP35299.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL391427; CAI14726.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL713867; CAI14726.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL713867; CAI16408.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL391427; CAI16408.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC007024; AAH07024.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC063574; AAH63574.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR I73676; I73676.
JC5240; JC5240.
S61516; S61516.
RefSeq NP_001345.1; -.
NP_995317.1; -.
UniGene Hs.460260
3D structure databases
PDB
1IHI; X-ray; 3.00 A; A/B=1-323.[ExPASy / RCSB / EBI]
1J96; X-ray; 1.25 A; A/B=2-323.[ExPASy / RCSB / EBI]
1XJB; X-ray; 1.90 A; A/B=2-323.[ExPASy / RCSB / EBI]
2HDJ; X-ray; 2.00 A; A/B=1-323.[ExPASy / RCSB / EBI]
2IPJ; X-ray; 1.80 A; A/B=3-323.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1IHI; -.
1J96; -.
1XJB; -.
2HDJ; -.
2IPJ; -.
ModBase P52895.
PTM databases
PhosphoSite P52895; -.
Organism-specific databases
H-InvDB HIX0008604; -.
HGNC HGNC:385; AKR1C2.
GenAtlas AKR1C2.
MIM 600450; gene. [NCBI / EBI]
PharmGKB PA24678; -.
GeneCards P52895.
Gene expression databases
CleanEx HS_AKR1C2; -.
GermOnline ENSG00000151632; Homo sapiens.
Ontologies
GO
GO:0032052; Molecular function: bile acid binding (inferred from direct assay from UniProtKB).
GO:0047115; Molecular function: trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity (inferred from direct assay from UniProtKB).
GO:0007586; Biological process: digestion (inferred from direct assay from UniProtKB).
GO:0006693; Biological process: prostaglandin metabolic process (inferred from direct assay from UniProtKB).
GO:0008202; Biological process: steroid metabolic process (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001395; Aldo/ket_red.
Graphical view of domain structure.
Gene3D G3DSA:3.20.20.100; Aldo/ket_red; 1.
PANTHER PTHR11732; Aldo/ket_red; 1.
Pfam PF00248; Aldo_ket_red; 1.
Pfam graphical view of domain structure.
PRINTS PR00069; ALDKETRDTASE.
ProDom PD000288; Aldo/ket_red; 1.
[Domain structure / List of seq. sharing at least 1 domain]
PROSITE PS00798; ALDOKETO_REDUCTASE_1; FALSE_NEG.
PS00062; ALDOKETO_REDUCTASE_2; 1.
PS00063; ALDOKETO_REDUCTASE_3; 1.
BLOCKS P52895.
ProtoNet P52895.
Genome annotation databases
Ensembl ENSG00000151632; Homo sapiens. [Contig view]
GeneID 1646; -.
KEGG hsa:1646; -.
Phylogenomic databases
HOGENOM P52895; -.
HOVERGEN P52895; -.
Other
DrugBank DB00157; NADH.
DB01586; Ursodeoxycholic acid.
NextBio 6772; -.
SOURCE AKR1C2; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase; Polymorphism; Steroid metabolism.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
CHAIN   1   323  323     Aldo-keto reductase family 1 member C2. PRO_0000124637
NP_BIND   216   280  65     NADP. 
ACT_SITE   55    55        Proton donor. 
BINDING   117   117        Substrate. 
SITE   84    84  1     Lowers pKa of active site Tyr (By similarity). 
VARIANT   172   172  1     L -> Q (in dbSNP:rs11474 [NCBI]). VAR_014748 [3D]
CONFLICT   46    46        F -> Y (in Ref. 3; AAB38486). 
CONFLICT   76    76        R -> S (in Ref. 12; AA sequence). 
CONFLICT   87    87        S -> C (in Ref. 12; AA sequence). 
CONFLICT   93    93        E -> EE (in Ref. 12; AA sequence). 
CONFLICT   111   111        V -> A (in Ref. 3; AAB38486). 
CONFLICT   164   164        G -> R (in Ref. 7; BAF82993). 
CONFLICT   179   179        K -> E (in Ref. 1; AAD14013 and 3; AAB38486). 
CONFLICT   185   185        K -> E (in Ref. 1; AAD14013 and 3; AAB38486). 
CONFLICT   188   188        C -> H (in Ref. 12; AA sequence). 
CONFLICT   193   193        C -> H (in Ref. 12; AA sequence). 
CONFLICT   319   319        F -> I (in Ref. 1; AAD14013 and 3; AAB38486). 
STRAND   7     9  3      
STRAND   15    22  8      
HELIX   32    44  13      
STRAND   48    50  3      
HELIX   53    55  3      
HELIX   58    70  13      
HELIX   76    78  3      
STRAND   80    85  6      
HELIX   87    89  3      
HELIX   92    94  3      
HELIX   95   106  12      
STRAND   111   116  6      
HELIX   144   156  13      
STRAND   159   167  9      
HELIX   170   177  8      
STRAND   187   192  6      
HELIX   200   208  9      
STRAND   212   217  6      
TURN   225   227  3      
HELIX   235   237  3      
HELIX   239   248  10      
HELIX   252   262  11      
STRAND   266   270  5      
HELIX   274   280  7      
HELIX   281   285  5      
HELIX   290   297  8      
HELIX   309   311  3      
Sequence information
Length: 323 AA [This is the length of the unprocessed precursor] Molecular weight: 36735 Da [This is the MW of the unprocessed precursor] CRC64: 0D7B6F983FCE85E1 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MDSKYQCVKL NDGHFMPVLG FGTYAPAEVP KSKALEAVKL AIEAGFHHID SAHVYNNEEQ 

        70         80         90        100        110        120 
VGLAIRSKIA DGSVKREDIF YTSKLWSNSH RPELVRPALE RSLKNLQLDY VDLYLIHFPV 

       130        140        150        160        170        180 
SVKPGEEVIP KDENGKILFD TVDLCATWEA MEKCKDAGLA KSIGVSNFNH RLLEMILNKP 

       190        200        210        220        230        240 
GLKYKPVCNQ VECHPYFNQR KLLDFCKSKD IVLVAYSALG SHREEPWVDP NSPVLLEDPV 

       250        260        270        280        290        300 
LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTS EEMKAIDGLN 

       310        320 
RNVRYLTLDI FAGPPNYPFS DEY 

P52895 in FASTA format

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View entry in raw text format (no links)
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