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Q91WR5 (AK1CL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aldo-keto reductase family 1 member C21

EC=1.1.1.-
Alternative name(s):
17-alpha-hydroxysteroid dehydrogenase
Short name=17-alpha-HSD
3(or 17)-alpha-hydroxysteroid dehydrogenase
EC=1.1.1.209
3-alpha-hydroxysteroid dehydrogenase
Dihydrodiol dehydrogenase type 1
Short name=DD1
Dihydrodiol dehydrogenase type 3
Short name=DD3
Gene names
Name:Akr1c21
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length323 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids. Ref.1 Ref.2 Ref.5 Ref.7 Ref.9

Catalytic activity

Androsterone + NAD(P)+ = 5-alpha-androstane-3,17-dione + NAD(P)H. Ref.1 Ref.7 Ref.9

Enzyme regulation

Inhibited by high concentrations of substrate. Ref.1

Subunit structure

Monomer. Ref.1

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Detected in kidney and brain. Ref.1 Ref.2

Sequence similarities

Belongs to the aldo/keto reductase family.

Biophysicochemical properties

Kinetic parameters:

KM=1.8 µM for NADP Ref.1 Ref.7

KM=19 µM for androstenedione

KM=0.5 µM for 5-beta-pregnane-3-alpha,20-alpha-diol

KM=0.5 µM for 5-beta-pregnane-3,20-dione

KM=0.6 µM for epitestosterone

KM=0.3 µM for androst-4-ene-3,17-dione

pH dependence:

Optimum pH is 10.0.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 323323Aldo-keto reductase family 1 member C21
PRO_0000326222

Regions

Nucleotide binding20 – 245NADP
Nucleotide binding166 – 1672NADP
Nucleotide binding216 – 2249NADP
Nucleotide binding270 – 28011NADP

Sites

Active site551Proton donor
Binding site311Substrate
Binding site501NADP
Binding site1171Substrate
Binding site1901NADP
Site841Lowers pKa of active site Tyr By similarity

Experimental info

Mutagenesis241A → Y: Reduces enzyme activity and affinity for substrate. Alters the stereospecificity, so that androstenedione is converted to testosterone. Ref.5
Mutagenesis311K → A: No effect on affinity for androstenedione. Slight increase of catalytic activity. Ref.7
Mutagenesis2221Q → N: Decreases affinity for NADP. Changes enzyme activity, leading to the production of testosterone and concomitantly reducing the production of epi-testosterone. Ref.9
Mutagenesis2241Y → D: Decreases affinity for NADP. Changes enzyme activity, leading to the production of testosterone and concomitantly reducing the production of epi-testosterone. Ref.9
Mutagenesis2241Y → F: No effect on enzyme activity. Decreases affinity for NADP. Ref.9
Sequence conflict271L → V in BAD18929. Ref.1
Sequence conflict271L → V in AAH13531. Ref.4
Sequence conflict271L → V in AAH91761. Ref.4
Sequence conflict601H → R in BAD18929. Ref.1
Sequence conflict601H → R in AAH13531. Ref.4
Sequence conflict601H → R in AAH91761. Ref.4
Sequence conflict911H → R in BAD18929. Ref.1
Sequence conflict911H → R in AAH13531. Ref.4
Sequence conflict911H → R in AAH91761. Ref.4
Sequence conflict1001E → V in BAD18929. Ref.1
Sequence conflict1001E → V in AAH13531. Ref.4
Sequence conflict1001E → V in AAH91761. Ref.4
Sequence conflict1701Y → S in BAD18929. Ref.1
Sequence conflict1701Y → S in AAH13531. Ref.4
Sequence conflict1701Y → S in AAH91761. Ref.4
Sequence conflict2941K → E in AAH61057. Ref.4

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Q91WR5 [UniParc].

Last modified March 18, 2008. Version 2.
Checksum: 0D598A0559EFBF11

FASTA32336,877
        10         20         30         40         50         60 
MNSKCHCVIL NDGNFIPVLG FGTALPLECP KSKAKELTKI AIDAGFHHFD SASVYNTEDH 

        70         80         90        100        110        120 
VGEAIRSKIA DGTVRREDIF YTSKVWCTSL HPELVRASLE RSLQKLQFDY VDLYLIHYPM 

       130        140        150        160        170        180 
ALKPGEENFP VDEHGKLIFD RVDLCATWEA MEKCKDAGLT KSIGVSNFNY RQLEMILNKP 

       190        200        210        220        230        240 
GLKYKPVCNQ VECHPYLNQM KLLDFCKSKD IVLVAYGVLG TQRYGGWVDQ NSPVLLDEPV 

       250        260        270        280        290        300 
LGSMAKKYNR TPALIALRYQ LQRGIVVLNT SLKEERIKEN MQVFEFQLSS EDMKVLDGLN 

       310        320 
RNMRYIPAAI FKGHPNWPFL DEY 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of two isoforms of mouse 3(17)alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase family."
Ishikura S., Usami N., Nakajima S., Shiraishi H., El-Kabbani O., Hara A.
Biol. Pharm. Bull. 27:1939-1945(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Strain: ICR.
Tissue: Kidney.
[2]"Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17-alpha-HSD) and its involvement in the biosynthesis of epitestosterone."
Bellemare V., Faucher F., Breton R., Luu-The V.
BMC Biochem. 6:12-12(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Strain: C57BL/6.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Embryo.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Kidney.
[5]"Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular determinants responsible for the unique 17alpha-reductive activity of this enzyme."
Faucher F., Pereira de Jesus-Tran K., Cantin L., Luu-The V., Labrie F., Breton R.
J. Mol. Biol. 364:747-763(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION, MUTAGENESIS OF ALA-24.
[6]"Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme."
Dhagat U., Carbone V., Chung R.P.-T., Schulze-Briese C., Endo S., Hara A., El-Kabbani O.
Acta Crystallogr. F 63:825-830(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH NADP.
[7]"Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently from other aldo-keto reductases: identification and characterization of amino acid residues critical for substrate binding."
Faucher F., Cantin L., Pereira de Jesus-Tran K., Lemieux M., Luu-The V., Labrie F., Breton R.
J. Mol. Biol. 369:525-540(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 6-323 IN COMPLEX WITH EPITESTOSTERONE, MUTAGENESIS OF LYS-31, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, FUNCTION.
[8]"Structure of the G225P/G226P mutant of mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) ternary complex: implications for the binding of inhibitor and substrate."
Dhagat U., Endo S., Mamiya H., Hara A., El-Kabbani O.
Acta Crystallogr. D 65:257-265(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH NADP.
[9]"Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme."
Dhagat U., Endo S., Mamiya H., Hara A., El-Kabbani O.
Acta Crystallogr. D 66:198-204(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANT ASP-224, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLN-222 AND TYR-224.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB178898 mRNA. Translation: BAD18929.1.
AY742217 mRNA. Translation: AAW65159.1.
AK020439 mRNA. Translation: BAB32101.1.
BC013531 mRNA. Translation: AAH13531.1.
BC061057 mRNA. Translation: AAH61057.1.
BC091761 mRNA. Translation: AAH91761.1.
CCDSCCDS26225.1.
RefSeqNP_084177.2. NM_029901.2.
UniGeneMm.27085.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2HE5X-ray2.90A/B/C/D1-323[»]
2HE8X-ray1.90A/B1-323[»]
2HEJX-ray1.35A/B1-323[»]
2IPFX-ray1.85A/B6-323[»]
2IPGX-ray1.90A/B5-323[»]
2P5NX-ray1.80A/B1-323[»]
3CV6X-ray2.10A/B1-323[»]
3FJNX-ray2.30A/B1-323[»]
DisProtDP00690.
ProteinModelPortalQ91WR5.
SMRQ91WR5. Positions 6-323.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000021628.

Chemistry

ChEMBLCHEMBL1075270.

PTM databases

PhosphoSiteQ91WR5.

Proteomic databases

MaxQBQ91WR5.
PaxDbQ91WR5.
PRIDEQ91WR5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021628; ENSMUSP00000021628; ENSMUSG00000021207.
GeneID77337.
KEGGmmu:77337.
UCSCuc007pjr.1. mouse.

Organism-specific databases

CTD77337.
MGIMGI:1924587. Akr1c21.

Phylogenomic databases

eggNOGCOG0656.
GeneTreeENSGT00750000117516.
HOGENOMHOG000250272.
HOVERGENHBG000020.
InParanoidQ91WR5.
OMANTEDHVG.
OrthoDBEOG70KGQF.
PhylomeDBQ91WR5.
TreeFamTF106492.

Enzyme and pathway databases

SABIO-RKQ91WR5.

Gene expression databases

BgeeQ91WR5.
CleanExMM_AKR1C21.
GenevestigatorQ91WR5.

Family and domain databases

Gene3D3.20.20.100. 1 hit.
InterProIPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERPTHR11732. PTHR11732. 1 hit.
PfamPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFPIRSF000097. AKR. 1 hit.
PRINTSPR00069. ALDKETRDTASE.
SUPFAMSSF51430. SSF51430. 1 hit.
PROSITEPS00062. ALDOKETO_REDUCTASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ91WR5.
NextBio346785.
PROQ91WR5.
SOURCESearch...

Entry information

Entry nameAK1CL_MOUSE
AccessionPrimary (citable) accession number: Q91WR5
Secondary accession number(s): Q6P8V0, Q9CX32
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: July 9, 2014
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot