Reviewed, UniProtKB/Swiss-Prot P23457 (DIDH_RAT)

Names and origin

Protein names

Recommended name:
    3-alpha-hydroxysteroid dehydrogenase
      Short name=3-alpha-HSD
    EC=1.1.1.213
Alternative name(s):
    Hydroxyprostaglandin dehydrogenase

Gene names

Name:

Akr1c9

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	322 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Besides being a 3-alpha-hydroxysteroid dehydrogenase, the enzyme can accomplish diverse functions: as quinone reductase, as an aromatic alcohol dehydrogenase, as dihydrodiol dehydrogenase, and as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase.
Catalytic activity	Androsterone + NAD(P)+ = 5-alpha-androstane-3,17-dione + NAD(P)H.
Enzyme regulation	Potently inhibited by the nonsteroidal anti-inflammatory drugs (NSAID).
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Tissue specificity	In brain, highest levels found in olfactory bulb. Moderate levels present in cerebellum, cerebral cortex, hypothalamus and pituitary. Low levels present in amygdala, brain stem, caudate putamen, cingulate cortex, hippocampus, midbrain, and thalamus. Ref.10
Sequence similarities	Belongs to the aldo/keto reductase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW steroid metabolic process Ref.2 Traceable author statement. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3-alpha-hydroxysteroid dehydrogenase (A-specific) 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 – 322

322

3-alpha-hydroxysteroid dehydrogenase

PRO_0000124654

Regions

Nucleotide binding

217 – 280

64

NADP

Sites

Active site

55

1

Proton donor

Binding site

117

1

Substrate

Site

84

1

Lowers pKa of active site Tyr By similarity

Amino acid modifications

Modified residue

1

1

Blocked amino end (Met)

Experimental info

Sequence conflict

108

1

L → Q in AAB19918. Ref.3

Sequence conflict

273 – 274

2

NA → KP in AAB19918. Ref.3

Sequence conflict

280

1

L → P in AAB19918. Ref.3

Secondary structure

1

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322

Helix Strand Turn

Details...

Helix

3 – 5

3

Beta strand

7 – 9

3

Beta strand

15 – 22

8

Helix

33 – 43

11

Beta strand

48 – 50

3

Turn

53 – 56

4

Helix

58 – 70

13

Helix

76 – 78

3

Beta strand

80 – 85

6

Helix

87 – 89

3

Helix

92 – 94

3

Helix

95 – 106

12

Beta strand

109 – 117

9

Beta strand

124 – 129

6

Helix

144 – 156

13

Beta strand

159 – 167

9

Helix

170 – 177

8

Beta strand

187 – 192

6

Helix

200 – 209

10

Beta strand

212 – 217

6

Turn

225 – 227

3

Helix

235 – 237

3

Helix

239 – 247

9

Helix

252 – 262

11

Beta strand

266 – 269

4

Helix

274 – 280

7

Turn

281 – 284

4

Helix

290 – 297

8

Helix

309 – 311

3

Sequences

	Sequence		Length	Mass (Da)
	P23457-1 [UniParc]. Last modified November 1, 1991. Version 1. Checksum: 592EFC584726A4F6	FASTA	322	37,028
	10 20 30 40 50 60 MDSISLRVAL NDGNFIPVLG FGTTVPEKVA KDEVIKATKI AIDNGFRHFD SAYLYEVEEE 70 80 90 100 110 120 VGQAIRSKIE DGTVKREDIF YTSKLWSTFH RPELVRTCLE KTLKSTQLDY VDLYIIHFPM 130 140 150 160 170 180 ALQPGDIFFP RDEHGKLLFE TVDICDTWEA MEKCKDAGLA KSIGVSNFNC RQLERILNKP 190 200 210 220 230 240 GLKYKPVCNQ VECHLYLNQS KMLDYCKSKD IILVSYCTLG SSRDKTWVDQ KSPVLLDDPV 250 260 270 280 290 300 LCAIAKKYKQ TPALVALRYQ LQRGVVPLIR SFNAKRIKEL TQVFEFQLAS EDMKALDGLN 310 320 RNFRYNNAKY FDDHPNHPFT DE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase." Pawlowski J.E., Huizinga M., Penning T.M. J. Biol. Chem. 266:8820-8825(1991) [PubMed: 1840601] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family." Stolz A., Rahimi-Kiani M., Ameis D., Chan E., Ronk M., Shively J.E. J. Biol. Chem. 266:15253-15257(1991) [PubMed: 1714456] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[3]	"Molecular cloning and expression of rat liver 3 alpha-hydroxysteroid dehydrogenase." Cheng K.-C., White P.C., Qin K.-N. Mol. Endocrinol. 5:823-828(1991) [PubMed: 1922097] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[4]	"Rat hepatic 3 alpha-hydroxysteroid dehydrogenase: expression of cDNA and physiological function in bile acid biosynthetic pathway." Usui E., Okuda K., Kato Y., Noshiro M. J. Biochem. 115:230-237(1994) [PubMed: 7515872] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Genomic structure of rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD, AKR1C9)." Lin H.K., Hung C.F., Moore M., Penning T.M. J. Steroid Biochem. Mol. Biol. 71:29-39(1999) [PubMed: 10619355] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley.
[6]	"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: Liver.
[7]	"Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase." Del Bello B., Maellaro E., Sugherini L., Santucci A., Comporti M., Casini A.F. Biochem. J. 304:385-390(1994) [PubMed: 7998972] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16; 121-135; 152-166 AND 203-217. Tissue: Liver.
[8]	"Isolation and partial characterization of a full-length cDNA clone for 3 alpha-hydroxysteroid dehydrogenase: a potential target enzyme for nonsteroidal anti-inflammatory drugs." Pawlowski J., Huizinga M., Penning T.M. Agents Actions 34:289-293(1991) [PubMed: 1793046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-169 AND 238-322.
[9]	"Affinity labeling of 3 alpha-hydroxysteroid dehydrogenase with 3 alpha-bromoacetoxyandrosterone and 11 alpha-bromoacetoxyprogesterone. Isolation and sequence of active site peptides containing reactive cysteines; sequence confirmation using nucleotide sequence from a cDNA clone." Penning T.M., Abrams W.R., Pawlowski J.E. J. Biol. Chem. 266:8826-8834(1991) [PubMed: 2026597] [Abstract] Cited for: PROTEIN SEQUENCE OF 162-171; 208-223 AND 232-246.
[10]	"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: TISSUE SPECIFICITY. Tissue: Brain.
[11]	"Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily." Hoog S.S., Pawlowski J.E., Alzari P.M., Penning T.M., Lewis M. Proc. Natl. Acad. Sci. U.S.A. 91:2517-2521(1994) [PubMed: 8146147] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). Tissue: Liver.
[12]	"Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+." Bennett M.J., Schlegel B.P., Jez J.M., Penning T.M., Lewis M. Biochemistry 35:10702-10711(1996) [PubMed: 8718859] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M64393 mRNA. Translation: AAA40605.1.
M61937 mRNA. Translation: AAA41077.1.
D17310 mRNA. Translation: BAA04132.1.
S57790 mRNA. Translation: AAB19918.1.
AF180334 , AF180326, AF180327, AF180328, AF180329, AF180330, AF180331, AF180332, AF180333 Genomic DNA. Translation: AAF25813.1.
BC091123 mRNA. Translation: AAH91123.1.
S35751 mRNA. Translation: AAB21512.1.
S35752 mRNA. Translation: AAB21513.1.

IPI

IPI00211100.

PIR

A39350.
PC2175.

RefSeq

NP_612556.1.

UniGene

Rn.10021
Rn.206655

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AFS	X-ray	2.50	A/B	1-322	[»]
1LWI	X-ray	2.70	A/B	1-322	[»]
1RAL	X-ray	3.00	A	1-308	[»]

ModBase

Search...

Proteomic databases

PRIDE

P23457.

Genome annotation databases

Ensembl

ENSRNOG00000017672. Rattus norvegicus. [Contig view]

GeneID

191574.

KEGG

rno:191574.

Organism-specific databases

RGD

708361. LOC191574.

Phylogenomic databases

HOVERGEN

P23457.

OMA

P23457. QLASEDM.

Enzyme and pathway databases

BRENDA

1.1.1.213. 248.

Gene expression databases

ArrayExpress

P23457.

GermOnline

ENSRNOG00000017672. Rattus norvegicus.

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...

Other Resources

NextBio

622656.

Entry information

Entry name

DIDH_RAT

Accession

Primary (citable) accession number: P23457
Secondary accession number(s): Q5BKC8, Q6LDE6, Q6LDE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	November 1, 1991
Last modified:	June 16, 2009
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)