Details of the Target

General Information of Target

Target ID LDTP03976
Target Name Aldo-keto reductase family 1 member C3 (AKR1C3)
Gene Name AKR1C3
Gene ID 8644
Synonyms
DDH1; HSD17B5; KIAA0119; PGFS; Aldo-keto reductase family 1 member C3; EC 1.1.1.-; EC 1.1.1.210; EC 1.1.1.53; EC 1.1.1.62; 17-beta-hydroxysteroid dehydrogenase type 5; 17-beta-HSD 5; 3-alpha-HSD type II, brain; 3-alpha-hydroxysteroid dehydrogenase type 2; 3-alpha-HSD type 2; EC 1.1.1.357; Chlordecone reductase homolog HAKRb; Dihydrodiol dehydrogenase 3; DD-3; DD3; Dihydrodiol dehydrogenase type I; HA1753; Prostaglandin F synthase; PGFS; EC 1.1.1.188; Testosterone 17-beta-dehydrogenase 5; EC 1.1.1.239, EC 1.1.1.64
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY
Target Type
Successful
Target Bioclass
Enzyme
Family
Aldo/keto reductase family
Subcellular location
Cytoplasm
Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone. 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 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone. Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol . 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 displays retinaldehyde reductase activity toward 9-cis-retinal.
TTD ID
T60857
Uniprot ID
P42330
DrugMap ID
TT5ZWB6
Ensemble ID
ENST00000380554.5
HGNC ID
HGNC:386
ChEMBL ID
CHEMBL4681

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
C32 SNV: p.R223Q .
ETK1 SNV: p.C206R .
HEPG2 SNV: p.I69T NAIA_5    Probe Info 
MFE319 Insertion: p.K105EfsTer8 DBIA    Probe Info 
NCIH1703 SNV: p.N198K DBIA    Probe Info 
RKO SNV: p.A269G DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 21 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
P1
 Probe Info  		2.95  LDD0452  [1]
P2
 Probe Info  		1.51  LDD0453  [1]
P8
 Probe Info  		2.86  LDD0455  [1]
STPyne
 Probe Info  		K185(5.26); K201(0.38); K209(8.97); K33(6.92)  LDD0277  [2]
OPA-S-S-alkyne
 Probe Info  		K161(2.19)  LDD3494  [3]
DBIA
 Probe Info  		C26(1.06)  LDD3314  [4]
W1
 Probe Info  		Q172(1.98); K209(2.12); S208(2.12)  LDD0237  [5]
m-APA
 Probe Info  		N.A.  LDD2231  [6]
4-Iodoacetamidophenylacetylene
 Probe Info  		C145(0.00); C242(0.00); C193(0.00); C188(0.00)  LDD0038  [7]
IA-alkyne
 Probe Info  		C206(0.00); C242(0.00); C193(0.00); C188(0.00)  LDD0036  [7]
Lodoacetamide azide
 Probe Info  		C206(0.00); C145(0.00); C242(0.00); C193(0.00)  LDD0037  [7]
BTD
 Probe Info  		N.A.  LDD0004  [8]
IPM
 Probe Info  		C193(0.00); C188(0.00); C242(0.00)  LDD0025  [9]
JW-RF-010
 Probe Info  		C188(0.00); C242(0.00); C193(0.00)  LDD0026  [9]
TFBX
 Probe Info  		C193(0.00); C206(0.00)  LDD0027  [9]
WYneN
 Probe Info  		C242(0.00); C193(0.00)  LDD0021  [8]
Acrolein
 Probe Info  		H304(0.00); H314(0.00)  LDD0217  [10]
NAIA_5
 Probe Info  		C206(0.00); C145(0.00); C242(0.00); C7(0.00)  LDD2223  [11]
HHS-465
 Probe Info  		N.A.  LDD2240  [12]
HHS-475
 Probe Info  		Y184(1.30)  LDD2238  [13]
HHS-482
 Probe Info  		Y110(0.80); Y184(1.25); Y216(1.25); Y24(1.22)  LDD2239  [13]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
A-DA
 Probe Info  		2.17  LDD0140  [14]
AEA-DA
 Probe Info  		6.02  LDD0146  [14]
Kambe_3
 Probe Info  		20.00  LDD0130  [15]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C188(0.79); C193(0.74)  LDD2117  [16]
 LDCM0083  Avasimibe A-549 2.77  LDD0143  [14]
 LDCM0108  Chloroacetamide HeLa H304(0.00); C188(0.00)  LDD0222  [10]
 LDCM0632  CL-Sc Hep-G2 C242(3.65); C7(0.63)  LDD2227  [11]
 LDCM0082  FK866 A-549 3.25  LDD0142  [14]
 LDCM0080  Flurbiprofen A-549 2.17  LDD0140  [14]
 LDCM0107  IAA HeLa H304(0.00); H314(0.00)  LDD0221  [10]
 LDCM0074  Kambe_cp66 PC-3 20.00  LDD0130  [15]
 LDCM0022  KB02 769-P C242(0.92); C26(0.87)  LDD2246  [4]
 LDCM0023  KB03 42-MG-BA C26(1.29)  LDD2661  [4]
 LDCM0024  KB05 IGR37 C26(1.06)  LDD3314  [4]
 LDCM0109  NEM HeLa H304(0.00); H48(0.00); H53(0.00); H314(0.00)  LDD0223  [10]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C188(0.85)  LDD2099  [16]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C188(1.04)  LDD2107  [16]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C193(0.83)  LDD2109  [16]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C193(0.76)  LDD2119  [16]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C188(1.12); C193(0.95)  LDD2123  [16]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C193(0.74)  LDD2125  [16]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C193(1.29)  LDD2136  [16]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C193(1.97)  LDD2144  [16]
 LDCM0081  Rofecoxib A-549 2.17  LDD0141  [14]
 LDCM0110  W12 Hep-G2 Q172(1.98); K209(2.12); S208(2.12)  LDD0237  [5]
 LDCM0111  W14 Hep-G2 S162(0.91); Q271(0.93); R51(1.02); Q208(1.06)  LDD0238  [5]
 LDCM0112  W16 Hep-G2 K270(0.96); S271(0.96); K209(1.18); S208(1.22)  LDD0239  [5]
 LDCM0113  W17 Hep-G2 K209(1.24); S208(1.24); E174(1.30); Q172(1.30)  LDD0240  [5]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Doxorubicin Small molecular drug DB00997
Fenofibrate Small molecular drug DB01039
Flufenamic Acid Small molecular drug D0B2WJ
Flufenamic Acid Small molecular drug DB02266
Indomethacin Small molecular drug DB00328
Lumateperone Small molecular drug DB06077
Methylprednisolone Small molecular drug DB00959
Nadh Small molecular drug DB00157
Olaparib Small molecular drug DB09074
Glycyrrhizic Acid . DB13751
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Asp-9521 . D0H7XJ
Investigative
Click To Hide/Show 18 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
2'-monophosphoadenosine 5'-diphosphoribose Small molecular drug D0J2FY
2,2-dibenzylcyclopentanol Small molecular drug D0V5AQ
2-(4-chlorobenzylidene)Cyclopentanone Small molecular drug D0MC5H
2-(4-chlorobenzylidene)Cyclopentyl Ethyl Ether Small molecular drug D00XMO
2-(4-chlorobenzylidene)Cyclopentylmethyl Ether Small molecular drug D0Q9RA
2-methyl-2,4-pentanediol Small molecular drug D06GOK
2-[(2,2-diphenylacetyl)Amino]Benzoic Acid Small molecular drug D03POE
3-bromo-5-phenylsalicylc Acid Small molecular drug D00DDO
3-phenylcyclopentanecarboxylic Acid Small molecular drug D0Z0IR
4-androstene-3-17-dione Small molecular drug D0M8RO
Acetate Ion Small molecular drug D0F2ME
Em-1424 Small molecular drug D0ZR1V
Em1396 Small molecular drug D0K9YS
M-phenoxybenzoic Acid For Cis-isomer Small molecular drug D0DF1Z
Prostaglandin D2 Small molecular drug DB02056
Rutin Small molecular drug D09ALJ
3-carboxamido-135(10)-estratrien-17(R)-spiro-2'(5'5'-dimethyl-6'oxo)Tetrahydropyran . DB07700
Nicotinamide Adenine Dinucleotide Phosphate . DB03461
Patented
Click To Hide/Show 13 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Beta-naphthylacetic Acids Derivative 1 Small molecular drug D0G8VB
Indomethacin Analog 1 Small molecular drug D0GY2Z
Indomethacin Analog 2 Small molecular drug D0F0PK
Indomethacin Analog 3 Small molecular drug D0E2TY
Isoquinolone Derivative 1 Small molecular drug D0Y7XJ
N-(Benzimidazole/Indole) Benzoic Acid Derivative 1 Small molecular drug D0S6TL
N-(Benzimidazole/Indole) Benzoic Acid Derivative 2 Small molecular drug D02JPV
N-(Benzimidazolylcarbonyl)-piperidine Derivative 1 Small molecular drug D0N3XY
N-(Indolylcarbonyl)-piperidine Derivative 1 Small molecular drug D0Q8RC
N-(Naphthylamino)-benzoate Derivative 1 Small molecular drug D0M6LX
N-(Phenylamino)-benzoate Derivative 1 Small molecular drug D05GKS
N-(Pyridinepyrroylylcarbonyl)-piperidine Derivative 1 Small molecular drug D0SM2O
Nitrogen/Sulfur-substituted Estrene Derivative 1 Small molecular drug D0PI1W
Discontinued
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Androstanedione Small molecular drug DB01561
Androstenedione Small molecular drug DB01536
Stanolone Small molecular drug DB02901

References

1 Comparison of Different Competitive Proteome Profiling Approaches in Target Identification of Covalent Inhibitors. Chembiochem. 2022 Dec 16;23(24):e202200389. doi: 10.1002/cbic.202200389. Epub 2022 Nov 22.
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 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
4 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
5 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.
6 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
7 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
8 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
9 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
10 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.
11 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
12 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010
13 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
14 A Global Map of Lipid-Binding Proteins and Their Ligandability in Cells. Cell. 2015 Jun 18;161(7):1668-80. doi: 10.1016/j.cell.2015.05.045.
15 Mapping the protein interaction landscape for fully functionalized small-molecule probes in human cells. J Am Chem Soc. 2014 Jul 30;136(30):10777-82. doi: 10.1021/ja505517t. Epub 2014 Jul 21.
16 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761