General Information of Target

Target ID LDTP02902
Target Name Aldo-keto reductase family 1 member C4 (AKR1C4)
Gene Name AKR1C4
Gene ID 1109
Synonyms
CHDR; Aldo-keto reductase family 1 member C4; EC 1.1.1.-; EC 1.1.1.209; EC 1.1.1.210; EC 1.1.1.51; EC 1.1.1.53; EC 1.1.1.62; 3-alpha-hydroxysteroid dehydrogenase type I; 3-alpha-HSD1; EC 1.1.1.357; 3alpha-hydroxysteroid 3-dehydrogenase; Chlordecone reductase; CDR; EC 1.1.1.225; Dihydrodiol dehydrogenase 4; DD-4; DD4; HAKRA
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDPKYQRVELNDGHFMPVLGFGTYAPPEVPRNRAVEVTKLAIEAGFRHIDSAYLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWCTFFQPQMVQPALESSLKKLQLDYVDLYLLHFPM
ALKPGETPLPKDENGKVIFDTVDLSATWEVMEKCKDAGLAKSIGVSNFNCRQLEMILNKP
GLKYKPVCNQVECHPYLNQSKLLDFCKSKDIVLVAHSALGTQRHKLWVDPNSPVLLEDPV
LCALAKKHKQTPALIALRYQLQRGVVVLAKSYNEQRIRENIQVFEFQLTSEDMKVLDGLN
RNYRYVVMDFLMDHPDYPFSDEY
Target Bioclass
Enzyme
Family
Aldo/keto reductase family
Subcellular location
Cytoplasm, cytosol
Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Liver specific enzyme that acts as an NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain. Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH. Acts preferentially as a 3-alpha-hydroxysteroid dehydrogenase (HSD) with a subsidiary 3-beta-HSD activity. Catalyzes efficiently the transformation of the potent androgen 5-alpha-dihydrotestosterone (5alpha-DHT or 17beta-hydroxy-5alpha-androstan-3-one) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Catalyzes the reduction of estrone into 17beta-estradiol but with low efficiency. Metabolizes a broad spectrum of natural and synthetic therapeutic steroid and plays an important role in metabolism of androgens, estrogens, progestereone and conjugated steroids. Catalyzes the biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leading to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route.
Uniprot ID
P17516
Ensemble ID
ENST00000263126.3
HGNC ID
HGNC:387
ChEMBL ID
CHEMBL4999

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 10 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info 
C154(0.00); C193(0.00); C188(0.00)  LDD0241  [1]
OPA-S-S-alkyne
 Probe Info 
K68(2.24); K75(2.78); K270(2.79)  LDD3494  [2]
DBIA
 Probe Info 
C242(0.90)  LDD3364  [3]
5E-2FA
 Probe Info 
N.A.  LDD2235  [4]
m-APA
 Probe Info 
N.A.  LDD2231  [4]
KY-26
 Probe Info 
N.A.  LDD0301  [5]
Acrolein
 Probe Info 
C242(0.00); H14(0.00); C206(0.00)  LDD0217  [6]
Crotonaldehyde
 Probe Info 
N.A.  LDD0219  [6]
Methacrolein
 Probe Info 
C242(0.00); C206(0.00)  LDD0218  [6]
NAIA_5
 Probe Info 
N.A.  LDD2223  [7]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DA-2
 Probe Info 
N.A.  LDD0073  [8]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa H14(0.00); C206(0.00)  LDD0222  [6]
 LDCM0107  IAA HeLa H14(0.00); C206(0.00)  LDD0221  [6]
 LDCM0022  KB02 769-P C242(0.83)  LDD2246  [3]
 LDCM0023  KB03 769-P C242(0.82)  LDD2663  [3]
 LDCM0024  KB05 NCI-N87 C242(0.90)  LDD3364  [3]
 LDCM0109  NEM HeLa N.A.  LDD0223  [6]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Lumateperone Small molecular drug DB06077
Methylprednisolone Small molecular drug DB00959
Nabumetone Small molecular drug DB00461
Nadh Small molecular drug DB00157
Norethisterone Small molecular drug DB00717
Glycyrrhizic Acid . DB13751

References

1 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
2 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
3 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
4 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
5 Direct Target Site Identification of a Sulfonyl-Triazole Covalent Kinase Probe by LC-MS Chemical Proteomics. Anal Chem. 2021 Sep 7;93(35):11946-11955. doi: 10.1021/acs.analchem.1c01591. Epub 2021 Aug 25.
6 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
7 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
8 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.