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Reviewed, UniProtKB/Swiss-Prot Q04828 (AK1C1_HUMAN)

Last modified November 25, 2008. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Aldo-keto reductase family 1 member C1
    EC=1.1.1.-
Alternative name(s):
    20-alpha-hydroxysteroid dehydrogenase
      Short name=20-alpha-HSD
    EC=1.1.1.149
    Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
    EC=1.3.1.20
    Dihydrodiol dehydrogenase 1/2
      Short name=DD1/DD2
    Chlordecone reductase homolog HAKRC
    High-affinity hepatic bile acid-binding protein
      Short name=HBAB
Gene names
Name: AKR1C1
Synonyms: DDH, DDH1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length323 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.

Catalytic activity

17-alpha,20-alpha-dihydroxypregn-4-en-3-one + NAD(P)(+) = 17-alpha-hydroxyprogesterone + NAD(P)H.

Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol + NADPH.

Enzyme regulation

Inhibited by hexestrol with an IC50 of 9.5 µM, 1,10-phenanthroline with an IC50 of 55 µM, 1,7-phenanthroline with an IC50 of 72 µM, flufenamic acid with an IC50 of 6.0 µM, indomethacin with an IC50 of 140 µM, ibuprofen with an IC50 of 950 µM, lithocholic acid with an IC50 of 25 µM, ursodeoxycholic acid with an IC50 of 340 µM and chenodeoxycholic acid with an IC50 of 570 µM.

Subunit structure

Monomer.

Subcellular location

Cytoplasm.

Tissue specificity

Expressed in all tissues tested including liver, prostate, testis, adrenal gland, brain, uterus, mammary gland and keratinocytes. Highest levels found in liver, mammary gland and brain.

Sequence similarities

Belongs to the aldo/keto reductase family.

Biophysicochemical properties

Kinetic parameters:

KM=5 µM for (s)-tetralol

KM=38 µM for (s)-indan-1-ol

KM=580 µM for benzene dihydrodiol

KM=3 µM for 5-beta-pregnane-3-alpha,20-alpha-diol

KM=3 µM for 5-beta-pregnan-20-alpha-ol-3-one

KM=12 µM for 4-pregnen-20-alpha-ol-3-one

KM=133 µM for 9-alpha,11-beta-PGF2

KM=2 µM for 5-beta-pregnan-3-alpha-ol-20-one

KM=1 µM for 5-beta-androstane-3,17-dione

KM=12 µM for PGD2

KM=0.6 µM for 20-alpha-hydroxyprogesterone (with NADH)

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 323323Aldo-keto reductase family 1 member C1
PRO_0000124633

Regions

Nucleotide binding13 – 2210NADP Potential
Nucleotide binding217 – 28064NADP By similarity

Sites

Active site551Proton donor By similarity
Binding site1171Substrate By similarity
Binding site3041Progesterone
Site541Important for substrate specificity By similarity
Site841Lowers pKa of active site Tyr By similarity
Site2221May be involved in the mediating step between the transformation of progesterone and the release of the cofactor

Experimental info

Mutagenesis1271E → D: 30-fold decrease in k(cat)/K(m) value for progesterone reduction; no effect on the K(m) value
Mutagenesis2221H → I: Marked decrease in k(cat)/K(m) value for progesterone; 24-fold decrease for progesterone reduction; 18-fold decrease for 20alpha-OHProg oxidation. 95-fold decrease in K(m) value for NADPH
Mutagenesis2221H → S: Marked decrease in k(cat)/K(m) value for progesterone; 10-fold decrease for progesterone reduction; 3-fold decrease for 20alpha-OHProg oxidation. 10-fold decrease in K(m) value for NADPH
Mutagenesis3041R → L: 70-fold decrease in progesterone reduction. No effect on DHT reduction
Mutagenesis3051Y → F: No effect on progesterone reduction
Mutagenesis3071T → V: No effect on progesterone reduction
Mutagenesis3091D → V: No effect on progesterone reduction
Sequence conflict31S → A Ref.4
Sequence conflict951V → D in AAD14012. Ref.4 Ref.10
Sequence conflict1581G → E in AAD14012. Ref.4 Ref.10
Sequence conflict171 – 1722RQ → ST in AAD14012. Ref.4 Ref.10
Sequence conflict183 – 1842KY → QV in AAD14012. Ref.4 Ref.10
Sequence conflict2221H → L in AAD14012. Ref.4 Ref.10
Sequence conflict3191F → I in AAD14012. Ref.4 Ref.10

Secondary structure

.................................................... 323
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04828-1 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: 9CB215478FBD29D5

FASTA32336,788
        10         20         30         40         50         60 
MDSKYQCVKL NDGHFMPVLG FGTYAPAEVP KSKALEATKL AIEAGFRHID SAHLYNNEEQ 

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

       130        140        150        160        170        180 
SVKPGEEVIP KDENGKILFD TVDLCATWEA VEKCKDAGLA KSIGVSNFNR RQLEMILNKP 

       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 

« Hide

References

« Hide 'large scale' references
[1]"cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family."
Stolz A., Hammond L., Lou H., Takikawa H., Ronk M., Shively J.E.
J. Biol. Chem. 268:10448-10457(1993) [PubMed: 8486699] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Genomic organization and chromosomal localization of a novel human hepatic dihydrodiol dehydrogenase with high affinity bile acid binding."
Lou H., Hammond L., Sharma V., Sparkes R.S., Lusis A.J., Stolz A.
J. Biol. Chem. 269:8416-8422(1994) [PubMed: 8132567] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[3]"Regulation of human dihydrodiol dehydrogenase by Michael acceptor xenobiotics."
Ciaccio P.J., Jaiswal A.K., Tew K.D.
J. Biol. Chem. 269:15558-15562(1994) [PubMed: 7515059] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Colon.
[4]"Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans."
Khanna M., Qin K.-N., Cheng K.-C.
J. Steroid Biochem. Mol. Biol. 53:41-46(1995) [PubMed: 7626489] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[5]"Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes."
Nishizawa M., Nakajima T., Yasuda K., Kanzaki H., Sasaguri Y., Watanabe K., Ito S.
Genes Cells 5:111-125(2000) [PubMed: 10672042] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[6]"Characterization of a human 20alpha-hydroxysteroid dehydrogenase."
Zhang Y., Dufort I., Rheault P., Luu-The V.
J. Mol. Endocrinol. 25:221-228(2000) [PubMed: 11013348] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Tissue: Skin fibroblast.
[7]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
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.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"The DNA sequence and comparative analysis of human chromosome 10."
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. expand/collapse author list , 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.
Nature 429:375-381(2004) [PubMed: 15164054] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung and Testis.
[10]"Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase."
Qin K.-N., New M.I., Cheng K.-C.
J. Steroid Biochem. Mol. Biol. 46:673-679(1993) [PubMed: 8274401] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-323.
Tissue: Liver.
[11]"Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells."
Hara A., Matsuura K., Tamada Y., Sato K., Miyabe Y., Deyashiki Y., Ishida N.
Biochem. J. 313:373-376(1996) [PubMed: 8573067] [Abstract]
Cited for: PROTEIN SEQUENCE OF 10-31; 40-61; 69-126; 137-153; 162-206; 209-230; 250-267; 271-289 AND 295-323, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[12]"Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder."
Deyashiki Y., Ogasawara A., Nakayama T., Nakanishi M., Miyabe Y., Sato K., Hara A.
Biochem. J. 299:545-552(1994) [PubMed: 8172617] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-323, PROTEIN SEQUENCE OF 18-31; 105-131; 176-193 AND 271-294.
Tissue: Liver.
[13]"Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids."
Couture J.-F., Legrand P., Cantin L., Luu-The V., Labrie F., Breton R.
J. Mol. Biol. 331:593-604(2003) [PubMed: 12899831] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH NADP AND 20ALPHA-HYDROXY-PROGESTERONE, MUTAGENESIS OF GLU-127; HIS-222; ARG-304; TYR-305; THR-307 AND ASP-309.
+Additional computationally mapped references.

Cross-references

Sequence databases

M86609 mRNA. Translation: AAB02880.1.
U05861