Q91WR5 (AK1CL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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-alpha-hydroxysteroid dehydrogenase
Dihydrodiol dehydrogenase type 1
Short name=DD1
Dihydrodiol dehydrogenase type 3
Short name=DD3

Gene names

Name:

Akr1c21

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into epitestosterone. 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.6
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.8 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.

Ontologies

Keywords
Biological process	Lipid metabolism Steroid metabolism
Cellular component	Cytoplasm
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	steroid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 323

323

Aldo-keto reductase family 1 member C21

PRO_0000326222

Regions

Nucleotide binding

13 – 24

12

NADP

Nucleotide binding

166 – 167

2

NADP

Nucleotide binding

216 – 224

9

NADP

Nucleotide binding

270 – 279

10

NADP

Sites

Active site

55

1

Proton donor

Binding site

31

1

Substrate

Binding site

50

1

NADP

Binding site

117

1

Substrate

Site

84

1

Lowers pKa of active site Tyr By similarity

Amino acid modifications

Modified residue

88

1

Phosphothreonine Ref.5

Modified residue

89

1

Phosphoserine Ref.5

Experimental info

Mutagenesis

24

1

A → Y: Reduces enzyme activity and affinity for substrate. Alters the stereospecificity, so that androstenedione is converted to testosterone. Ref.6

Mutagenesis

31

1

K → A: No effect on affinity for androstenedione. Slight increase of catalytic activity. Ref.8

Sequence conflict

27

1

L → V in BAD18929. Ref.1

Sequence conflict

27

1

L → V in AAH13531. Ref.4

Sequence conflict

27

1

L → V in AAH91761. Ref.4

Sequence conflict

60

1

H → R in BAD18929. Ref.1

Sequence conflict

60

1

H → R in AAH13531. Ref.4

Sequence conflict

60

1

H → R in AAH91761. Ref.4

Sequence conflict

91

1

H → R in BAD18929. Ref.1

Sequence conflict

91

1

H → R in AAH13531. Ref.4

Sequence conflict

91

1

H → R in AAH91761. Ref.4

Sequence conflict

100

1

E → V in BAD18929. Ref.1

Sequence conflict

100

1

E → V in AAH13531. Ref.4

Sequence conflict

100

1

E → V in AAH91761. Ref.4

Sequence conflict

170

1

Y → S in BAD18929. Ref.1

Sequence conflict

170

1

Y → S in AAH13531. Ref.4

Sequence conflict

170

1

Y → S in AAH91761. Ref.4

Sequence conflict

294

1

K → E in AAH61057. Ref.4

Secondary structure

1

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323

Helix Strand Turn

Details...

Beta strand

7 – 9

3

Beta strand

15 – 22

8

Helix

33 – 44

12

Beta strand

48 – 50

3

Helix

53 – 55

3

Helix

58 – 70

13

Helix

76 – 78

3

Beta strand

80 – 85

6

Helix

87 – 89

3

Turn

92 – 94

3

Helix

95 – 106

12

Beta strand

111 – 117

7

Helix

144 – 156

13

Beta strand

159 – 167

9

Helix

170 – 177

8

Beta strand

187 – 192

6

Helix

200 – 208

9

Beta strand

212 – 216

5

Turn

225 – 227

3

Helix

235 – 237

3

Helix

239 – 248

10

Helix

252 – 261

10

Turn

262 – 264

3

Beta strand

266 – 269

4

Helix

274 – 280

7

Helix

281 – 285

5

Helix

290 – 297

8

Helix

309 – 311

3

Sequences

	Sequence		Length	Mass (Da)
	Q91WR5 [UniParc]. Last modified March 18, 2008. Version 2. Checksum: 0D598A0559EFBF11	FASTA	323	36,877
	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

References

	« Hide 'large scale' referencesShow '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: 15577209] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 16018803] [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. , 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: 16141072] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Kidney.
[5]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed: 17203969] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-88 AND SER-89, MASS SPECTROMETRY. Tissue: Liver.
[6]	"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: 17034817] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION, MUTAGENESIS OF ALA-24.
[7]	"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: 17909281] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH NADP.
[8]	"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: 17442338] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 6-323 IN COMPLEX WITH EPITESTOSTERONE, MUTAGENESIS OF LYS-31, BIOPHYSICOCHEMICAL PROPERTIES.
+	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.

IPI

IPI00830240.

RefSeq

NP_084177.2. NM_029901.2.

UniGene

Mm.27085.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HE5	X-ray	2.90	A/B/C/D	1-323	[»]
2HE8	X-ray	1.90	A/B	1-323	[»]
2HEJ	X-ray	1.35	A/B	1-323	[»]
2IPF	X-ray	1.85	A/B	6-323	[»]
2IPG	X-ray	1.90	A/B	5-323	[»]
2P5N	X-ray	1.80	A/B	1-323	[»]
3CV6	X-ray	2.10	A/B	1-323	[»]
3FJN	X-ray	2.30	A/B	1-323	[»]

ProteinModelPortal

Q91WR5.

SMR

Q91WR5. Positions 6-323.

ModBase

Search...

Protein-protein interaction databases

STRING

Q91WR5.

PTM databases

PhosphoSite

Q91WR5.

Proteomic databases

PRIDE

Q91WR5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000021628; ENSMUSP00000021628; ENSMUSG00000021207.

GeneID

77337.

KEGG

mmu:77337.

UCSC

uc007pjr.1. mouse.

Organism-specific databases

CTD

77337.

MGI

MGI:1924587. Akr1c21.

Phylogenomic databases

eggNOG

roNOG15221.

GeneTree

ENSGT00550000074107.

HOGENOM

HBG605727.

HOVERGEN

HBG000020.

InParanoid

Q91WR5.

OMA

NTEDHVG.

OrthoDB

EOG4QJRNQ.

PhylomeDB

Q91WR5.

Gene expression databases

ArrayExpress

Q91WR5.

Bgee

Q91WR5.

CleanEx

MM_AKR1C21.

Genevestigator

Q91WR5.

Family and domain databases

InterPro

IPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]

Gene3D

G3DSA:3.20.20.100. Aldo/ket_red. 1 hit.

PANTHER

PTHR11732. Aldo/ket_red. 1 hit.

Pfam

PF00248. Aldo_ket_red. 1 hit.
[Graphical view]

PIRSF

PIRSF000097. AKR. 1 hit.

PRINTS

PR00069. ALDKETRDTASE.

SUPFAM

SSF51430. Aldo/ket_red. 1 hit.

PROSITE

PS00798. ALDOKETO_REDUCTASE_1. False negative.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

346785.

SOURCE

Search...

Entry information

Entry name

AK1CL_MOUSE

Accession

Primary (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:	September 21, 2011
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program