Reviewed, UniProtKB/Swiss-Prot Q95JH4 (AK1C4_MACFU)

Names and origin

Protein names

Recommended name:
    Aldo-keto reductase family 1 member C4
    EC=1.1.1.-
Alternative name(s):
    Chlordecone reductase
      Short name=CDR
    EC=1.1.1.225
    3-alpha-hydroxysteroid dehydrogenase type I
    EC=1.1.1.50
    3-alpha-HSD1
    Dihydrodiol dehydrogenase 4
      Short name=DD-4
      Short name=DD4

Gene names

Name:

AKR1C4

Organism

Macaca fuscata fuscata (Japanese macaque)

Taxonomic identifier

9543 [NCBI]

Taxonomic lineage

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

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	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. 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 structure	Monomer By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	High expression in liver. Also expressed in kidney. Ref.1
Sequence similarities	Belongs to the aldo/keto reductase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3-alpha-hydroxysteroid dehydrogenase (B-specific) activity Inferred from electronic annotation. Source: EC chlordecone 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	Aldo-keto reductase family 1 member C4		PRO_0000124642
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	Important for substrate specificity By similarity
	Site	84	1	Lowers pKa of active site Tyr By similarity
Amino acid modifications
	Modified residue	196	1	Phosphotyrosine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q95JH4-1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 38382E7AD7EB7AFA	FASTA	323	37,103
	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

References

[1]

"Molecular characterization of two monkey dihydrodiol dehydrogenases." Higaki Y., Kamiya T., Usami N., Shintani S., Shiraishi H., Ishikura S., Yamamoto I., Hara A. Drug Metab. Pharmacokinet. 17:348-356(2002) [PubMed: 15618685] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, TISSUE SPECIFICITY. Tissue: Liver.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB070212 mRNA. Translation: BAB63209.2.
3D structure databases
HSSP	HSSP built from PDB template 1MRQ based on UniProtKB Q04828.
SMR	Q95JH4. Positions 1-323.
ModBase	Search...
Phylogenomic databases
HOVERGEN	Q95JH4.
Enzyme and pathway databases
BRENDA	1.1.1.225. 276174. 1.1.1.50. 276174. 1.3.1.20. 276174.
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

AK1C4_MACFU

Accession

Primary (citable) accession number: Q95JH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 40 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)