Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

3-alpha-hydroxysteroid dehydrogenase

Gene

Akr1c9

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

A 3-alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H.

Enzyme regulationi

Potently inhibited by the nonsteroidal anti-inflammatory drugs (NSAID).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei50 – 501NADP1 Publication
Active sitei55 – 551Proton donor
Sitei84 – 841Lowers pKa of active site TyrBy similarity
Binding sitei117 – 1171Substrate
Binding sitei190 – 1901NADP1 Publication
Binding sitei227 – 2271Substrate

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi20 – 245NADP1 Publication
Nucleotide bindingi166 – 1672NADP1 Publication
Nucleotide bindingi216 – 2216NADP1 Publication
Nucleotide bindingi270 – 28011NADP1 PublicationAdd
BLAST

GO - Molecular functioni

  • androsterone dehydrogenase (B-specific) activity Source: UniProtKB-EC
  • steroid dehydrogenase activity Source: RGD

GO - Biological processi

  • hippocampus development Source: RGD
  • steroid metabolic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-14305.
BRENDAi1.1.1.213. 5301.
1.6.5.10. 5301.
ReactomeiR-RNO-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-RNO-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
R-RNO-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
R-RNO-2162123. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
R-RNO-5365859. RA biosynthesis pathway.
R-RNO-975634. Retinoid metabolism and transport.
SABIO-RKP23457.

Names & Taxonomyi

Protein namesi
Recommended name:
3-alpha-hydroxysteroid dehydrogenase (EC:1.1.1.50)
Short name:
3-alpha-HSD
Alternative name(s):
Hydroxyprostaglandin dehydrogenase
Gene namesi
Name:Akr1c9
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi708361. LOC191574.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL1075221.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 3223223-alpha-hydroxysteroid dehydrogenasePRO_0000124654Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11Blocked amino end (Met)

Proteomic databases

PaxDbiP23457.
PRIDEiP23457.

PTM databases

iPTMnetiP23457.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

GenevisibleiP23457. RN.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

MINTiMINT-4567560.
STRINGi10116.ENSRNOP00000023835.

Structurei

Secondary structure

1
322
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 53Combined sources
Beta strandi7 – 93Combined sources
Turni11 – 133Combined sources
Beta strandi15 – 228Combined sources
Turni28 – 303Combined sources
Helixi33 – 4311Combined sources
Beta strandi48 – 503Combined sources
Turni53 – 564Combined sources
Helixi58 – 7013Combined sources
Helixi76 – 783Combined sources
Beta strandi80 – 856Combined sources
Helixi87 – 893Combined sources
Helixi92 – 943Combined sources
Helixi95 – 10612Combined sources
Beta strandi109 – 1179Combined sources
Beta strandi124 – 1296Combined sources
Beta strandi131 – 1377Combined sources
Helixi144 – 15613Combined sources
Beta strandi159 – 1679Combined sources
Helixi170 – 1778Combined sources
Beta strandi187 – 1926Combined sources
Helixi200 – 20910Combined sources
Beta strandi212 – 2176Combined sources
Turni225 – 2273Combined sources
Helixi235 – 2373Combined sources
Helixi239 – 2479Combined sources
Helixi252 – 26211Combined sources
Beta strandi266 – 2694Combined sources
Helixi274 – 2807Combined sources
Turni281 – 2844Combined sources
Helixi290 – 2978Combined sources
Helixi309 – 3113Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AFSX-ray2.50A/B1-322[»]
1LWIX-ray2.70A/B1-322[»]
1RALX-ray3.00A1-308[»]
ProteinModelPortaliP23457.
SMRiP23457. Positions 1-319.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23457.

Family & Domainsi

Sequence similaritiesi

Belongs to the aldo/keto reductase family.Curated

Phylogenomic databases

eggNOGiKOG1577. Eukaryota.
COG0656. LUCA.
GeneTreeiENSGT00760000119041.
HOGENOMiHOG000250272.
HOVERGENiHBG000020.
InParanoidiP23457.
OMAiMLDYCKS.
OrthoDBiEOG70KGQF.
PhylomeDBiP23457.
TreeFamiTF106492.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red/Kv-b.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 2 hits.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFiPIRSF000097. AKR. 1 hit.
PRINTSiPR00069. ALDKETRDTASE.
SUPFAMiSSF51430. SSF51430. 1 hit.
PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P23457-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSISLRVAL NDGNFIPVLG FGTTVPEKVA KDEVIKATKI AIDNGFRHFD
60 70 80 90 100
SAYLYEVEEE VGQAIRSKIE DGTVKREDIF YTSKLWSTFH RPELVRTCLE
110 120 130 140 150
KTLKSTQLDY VDLYIIHFPM ALQPGDIFFP RDEHGKLLFE TVDICDTWEA
160 170 180 190 200
MEKCKDAGLA KSIGVSNFNC RQLERILNKP GLKYKPVCNQ VECHLYLNQS
210 220 230 240 250
KMLDYCKSKD IILVSYCTLG SSRDKTWVDQ KSPVLLDDPV LCAIAKKYKQ
260 270 280 290 300
TPALVALRYQ LQRGVVPLIR SFNAKRIKEL TQVFEFQLAS EDMKALDGLN
310 320
RNFRYNNAKY FDDHPNHPFT DE
Length:322
Mass (Da):37,028
Last modified:November 1, 1991 - v1
Checksum:i592EFC584726A4F6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081L → Q in AAB19918 (PubMed:1922097).Curated
Sequence conflicti273 – 2742NA → KP in AAB19918 (PubMed:1922097).Curated
Sequence conflicti280 – 2801L → P in AAB19918 (PubMed:1922097).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA39350.
PC2175.
RefSeqiNP_612556.1. NM_138547.3.
UniGeneiRn.10021.
Rn.206655.

Genome annotation databases

EnsembliENSRNOT00000023835; ENSRNOP00000023835; ENSRNOG00000017672.
GeneIDi191574.
KEGGirno:191574.
UCSCiRGD:708361. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA39350.
PC2175.
RefSeqiNP_612556.1. NM_138547.3.
UniGeneiRn.10021.
Rn.206655.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AFSX-ray2.50A/B1-322[»]
1LWIX-ray2.70A/B1-322[»]
1RALX-ray3.00A1-308[»]
ProteinModelPortaliP23457.
SMRiP23457. Positions 1-319.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4567560.
STRINGi10116.ENSRNOP00000023835.

Chemistry

ChEMBLiCHEMBL1075221.

PTM databases

iPTMnetiP23457.

Proteomic databases

PaxDbiP23457.
PRIDEiP23457.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000023835; ENSRNOP00000023835; ENSRNOG00000017672.
GeneIDi191574.
KEGGirno:191574.
UCSCiRGD:708361. rat.

Organism-specific databases

CTDi105387.
RGDi708361. LOC191574.

Phylogenomic databases

eggNOGiKOG1577. Eukaryota.
COG0656. LUCA.
GeneTreeiENSGT00760000119041.
HOGENOMiHOG000250272.
HOVERGENiHBG000020.
InParanoidiP23457.
OMAiMLDYCKS.
OrthoDBiEOG70KGQF.
PhylomeDBiP23457.
TreeFamiTF106492.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-14305.
BRENDAi1.1.1.213. 5301.
1.6.5.10. 5301.
ReactomeiR-RNO-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-RNO-193775. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
R-RNO-193807. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
R-RNO-2162123. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
R-RNO-5365859. RA biosynthesis pathway.
R-RNO-975634. Retinoid metabolism and transport.
SABIO-RKP23457.

Miscellaneous databases

EvolutionaryTraceiP23457.
PROiP23457.

Gene expression databases

GenevisibleiP23457. RN.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red/Kv-b.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 2 hits.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFiPIRSF000097. AKR. 1 hit.
PRINTSiPR00069. ALDKETRDTASE.
SUPFAMiSSF51430. SSF51430. 1 hit.
PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
  13. "Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase."
    Bennett M.J., Albert R.H., Jez J.M., Ma H., Penning T.M., Lewis M.
    Structure 5:799-812(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH NADP AND TESTOSTERONE.

Entry informationi

Entry nameiDIDH_RAT
AccessioniPrimary (citable) accession number: P23457
Secondary accession number(s): Q5BKC8, Q6LDE6, Q6LDE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 8, 2016
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.