EC 1.1.1.-
Chlordecone reductase
CDR
EC 1.1.1.225
3-alpha-hydroxysteroid dehydrogenase type I
EC 1.1.1.50
3-alpha-HSD1
Dihydrodiol dehydrogenase 4
DD-4
DD4

Gene name

Name:

AKR1C4

From

Macaca fuscata fuscata (Japanese macaque)

[TaxID: 9543]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Cercopithecidae; Cercopithecinae; Macaca.

Protein existence

1: Evidence at protein level;

References

[1]

NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND TISSUE SPECIFICITY.
TISSUE=Liver;
DOI=10.2133/dmpk.17.348; PubMed=15618685 [NCBI, ExPASy, EBI, Israel, Japan]
Higaki Y., Kamiya T., Usami N., Shintani S., Shiraishi H., Ishikura S., Yamamoto I., Hara A.;
"Molecular characterization of two monkey dihydrodiol dehydrogenases.";
Drug Metab. Pharmacokinet. 17:348-356(2002).

Comments

FUNCTION: Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid dehydrogenase activity. The biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route. Can oxidize both 3-alpha- and 20-alpha-hydroxysteroids with preference for 3-alpha-hydroxypreganes and 3-alpha-hydroxyandrostanes. Non-steroid substrates include R-tetralol and trans-benzene dihydroliol. Reduces both 3-ketoandrostanes and 3-ketopregnanes. Lower activity towards 20-ketopregnanes.
CATALYTIC ACTIVITY: Chlordecone alcohol + NADP⁺ = chlordecone + NADPH.
CATALYTIC ACTIVITY: Androsterone + NAD(P)⁺ = 5-alpha-androstane-3,17-dione + NAD(P)H.
ENZYME REGULATION: Potently inhibited by benzbromarone, 3',3", 5', 5"-tetrabromophenolphthalein (TBPP) and o-cresolphthalein.
SUBUNIT: Monomer (By similarity).
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
TISSUE SPECIFICITY: High expression in liver. Also expressed in kidney.
SIMILARITY: Belongs to the aldo/keto reductase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AB070212; BAB63209.2; -; mRNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

3D structure databases

HSSP

Q04828; 1MRQ. [HSSP ENTRY / PDB]

SMR

Q95JH4; 1-323.

ModBase

Q95JH4.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-KW).
GO:0047042;	Molecular function: 3-alpha-hydroxysteroid dehydrogenase (B-specific) activity (inferred from electronic annotation from EC).
GO:0047743;	Molecular function: chlordecone reductase activity (inferred from electronic annotation from EC).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR001395; Aldo/ket_red.
Graphical view of domain structure.

Gene3D

G3DSA:3.20.20.100; Aldo/ket_red; 1.

PANTHER

PTHR11732; Aldo/ket_red; 1.

Pfam

PF00248; Aldo_ket_red; 1.
Pfam graphical view of domain structure.

PRINTS

PR00069; ALDKETRDTASE.

ProDom

PD000288; Aldo/ket_red; 1.
[Domain structure / List of seq. sharing at least 1 domain]

PROSITE

PS00798; ALDOKETO_REDUCTASE_1; 1.
PS00062; ALDOKETO_REDUCTASE_2; 1.
PS00063; ALDOKETO_REDUCTASE_3; 1.

ProtoNet

Q95JH4.

Phylogenomic databases

HOVERGEN

Q95JH4; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Cytoplasm; NADP; Oxidoreductase; Phosphoprotein.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 323`	`323`	`Aldo-keto reductase family 1 member C4.`	`PRO_0000124642`
`NP_BIND`	`13 22`	`10`	`NADP (Potential).`
`NP_BIND`	`217 280`	`64`	`NADP (By similarity).`
`ACT_SITE`	`55 55`		`Proton donor (By similarity).`
`BINDING`	`117 117`		`Substrate (By similarity).`
`SITE`	`54 54`	`1`	`Important for substrate specificity (By similarity).`
`SITE`	`84 84`	`1`	`Lowers pKa of active site Tyr (By similarity).`
`MOD_RES`	`196 196`		`Phosphotyrosine (By similarity).`

Sequence information

Length: 323 AA [This is the length of the unprocessed precursor]

Molecular weight: 37103 Da [This is the MW of the unprocessed precursor]

CRC64: 38382E7AD7EB7AFA [This is a checksum on the sequence]

        10         20         30         40         50         60 
MDPKYQRVAL NDGHFMPVLG FGSYAPPEVP RNRVVEVTKL AIEAGFRHID SAYLYNNEEQ 

        70         80         90        100        110        120 
VGLAIRSKIA DGSVKREDIF YTSKLWCTFF RPQLVQPALE SSLKKLQLDY VDLYLIHFPM 

       130        140        150        160        170        180 
ALKPGETPLP KDENGKVMFD TVDLCAIWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNNP 

       190        200        210        220        230        240 
GLKYKPVCNQ VECHPYLNQS KLLDFCKSKD IVLVAHSALG TQRHKLWVDQ NSPALLEDPV 

       250        260        270        280        290        300 
LCALAKKHKR SPALIALRYQ LQRGVVVLAK SYNEQRIREN VQVFEFQLTS EDMKVLDDLN 

       310        320 
RNFRYVVMDF LVDHPDYPFS DEY

Q95JH4 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools