Reviewed, UniProtKB/Swiss-Prot P80508 (PE2R_RABIT)

Names and origin

Protein names

Recommended name:
    Prostaglandin-E(2) 9-reductase
    EC=1.1.1.189
Alternative name(s):
    20-alpha-hydroxysteroid dehydrogenase
      Short name=20-alpha-HSD
    EC=1.1.1.149

Gene names

Name:

AKR1C5

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Can convert prostaglandin E2 to prostaglandin F2-alpha.
Catalytic activity	(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH. 17-alpha,20-alpha-dihydroxypregn-4-en-3-one + NAD(P)+ = 17-alpha-hydroxyprogesterone + NAD(P)H.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the aldo/keto reductase family.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis Prostaglandin biosynthesis
Cellular component	Cytoplasm
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW prostaglandin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	20-alpha-hydroxysteroid dehydrogenase activity Inferred from electronic annotation. Source: EC prostaglandin-E2 9-reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 323

323

Prostaglandin-E(2) 9-reductase

PRO_0000124651

Regions

Nucleotide binding

13 – 22

10

NADP Potential

Nucleotide binding

217 – 280

64

NADP By similarity

Sites

Active site

55

1

Proton donor By similarity

Binding site

117

1

Substrate By similarity

Site

54

1

Required for substrate specificity

Site

84

1

Lowers pKa of active site Tyr By similarity

Experimental info

Mutagenesis

54

1

F → L: 49% reduction in 20alpha-HSD activity; little effect on 3-alpha-HSD. Ref.4

Mutagenesis

54

1

F → V: 73% reduction in 20alpha-HSD activity; little effect on 3-alpha-HSD. Ref.4

Mutagenesis

306

1

V → F: Greatly reduced 3alpha-HSD activity toward DHT; little effect on 20alpha-HSD activity. Ref.4

Secondary structure

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323

Helix Strand Turn

Details...

Helix

3 – 5

3

Beta strand

7 – 9

3

Beta strand

15 – 22

8

Helix

31 – 44

14

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

Helix

92 – 106

15

Beta strand

111 – 117

7

Helix

144 – 156

13

Beta strand

159 – 167

9

Helix

170 – 177

8

Beta strand

188 – 192

5

Helix

200 – 208

9

Beta strand

212 – 217

6

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 – 281

8

Helix

282 – 285

4

Helix

290 – 297

8

Helix

309 – 311

3

Beta strand

318 – 321

4

Sequences

	Sequence		Length	Mass (Da)
	P80508-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 110ADD9FF56061B7	FASTA	323	36,670
	10 20 30 40 50 60 MDPKFQRVAL SDGHFIPVLG FGTYAPEEVP KSKAMEATKI AIDAGFRHID SAYFYKNEKE 70 80 90 100 110 120 VGLAIRSKIA DGTVKREDIF YTSKLWCTFH RPELVRPSLE DSLKNLQLDY VDLYIIHFPT 130 140 150 160 170 180 ALKPGVEIIP TDEHGKAIFD TVDICATWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNKP 190 200 210 220 230 240 GLKYKPVCNQ VECHPYLNQG KLLEFCKSKG IVLVAYSALG SHREPEWVDQ SAPVLLEDPL 250 260 270 280 290 300 IGALAKKHQQ TPALIALRYQ LQRGIVVLAK SFTEKRIKEN IQVFEFQLPS EDMKVIDSLN 310 320 RNFRYVTADF AIGHPNYPFS DEY

References

[1]	"Molecular cloning and expression of an abundant rabbit ovarian protein with 20 alpha-hydroxysteroid dehydrogenase activity." Lacy W.R., Washenick K.J., Cook R.G., Dunbar B.S. Mol. Endocrinol. 7:58-66(1993) [PubMed: 8446108] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: New Zealand white. Tissue: Ovary.
[2]	Erratum Lacy W.R., Dunbar B.S. Mol. Endocrinol. 7:1239-1239(1993) [PubMed: 8247025] [Abstract]
[3]	"Prostaglandin-E2 9-reductase from corpus luteum of pseudopregnant rabbit is a member of the aldo-keto reductase superfamily featuring 20 alpha-hydroxysteroid dehydrogenase activity." Wintergalen N., Thole H.H., Galla H.-J., Schlegel W. Eur. J. Biochem. 234:264-270(1995) [PubMed: 8529651] [Abstract] Cited for: PROTEIN SEQUENCE OF 134-170 AND 279-314. Tissue: Corpus luteum.
[4]	"Loop relaxation, a mechanism that explains the reduced specificity of rabbit 20alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamily." Couture J.-F., Legrand P., Cantin L., Labrie F., Luu-The V., Breton R. J. Mol. Biol. 339:89-102(2004) [PubMed: 15123423] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEX WITH NADPH; NADP AND TESTOSTERONE, MUTAGENESIS OF PHE-54 AND VAL-306.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L17006 mRNA. Translation: AAA31155.1.

PIR

A45366.

RefSeq

NP_001075719.1.

UniGene

Ocu.3559

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q13	X-ray	2.08	A/B	1-323	[»]
1Q5M	X-ray	1.32	A/B	2-323	[»]

ModBase

Search...

Genome annotation databases

GeneID

100009071.

Phylogenomic databases

HOVERGEN

P80508.

Enzyme and pathway databases

BRENDA

1.1.1.149. 255.
1.1.1.189. 255.

Family and domain databases

InterPro

IPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
[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]

ProDom

PD000288. Aldo/ket_red. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

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

ProtoNet

Search...

Entry information

Entry name

PE2R_RABIT

Accession

Primary (citable) accession number: P80508

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	June 16, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)