Details of the Target

General Information of Target

Target ID LDTP04543
Target Name Aldo-keto reductase family 1 member C2 (AKR1C2)
Gene Name AKR1C2
Gene ID 1646
Synonyms
DDH2; Aldo-keto reductase family 1 member C2; EC 1.-.-.-; EC 1.1.1.112; EC 1.1.1.209; EC 1.1.1.53; EC 1.1.1.62; EC 1.3.1.20; 3-alpha-HSD3; Chlordecone reductase homolog HAKRD; Dihydrodiol dehydrogenase 2; DD-2; DD2; Dihydrodiol dehydrogenase/bile acid-binding protein; DD/BABP; Type III 3-alpha-hydroxysteroid dehydrogenase; EC 1.1.1.357
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV
SVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKP
GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN
RNVRYLTLDIFAGPPNYPFSDEY
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. Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH. Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens. Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Also specifically able to produce 17beta-hydroxy-5alpha-androstan-3-one/5alphaDHT. May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate. Displays affinity for bile acids.
Uniprot ID
P52895
Ensemble ID
ENST00000380753.9
HGNC ID
HGNC:385
ChEMBL ID
CHEMBL5847

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
MEWO SNV: p.R91Ter; p.D229N .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 19 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info  		K161(7.69)  LDD0277  [1]
DBIA
 Probe Info  		C242(0.85)  LDD3312  [2]
BTD
 Probe Info  		C188(1.02)  LDD2093  [3]
5E-2FA
 Probe Info  		H14(0.00); H170(0.00)  LDD2235  [4]
m-APA
 Probe Info  		N.A.  LDD2231  [4]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [5]
IA-alkyne
 Probe Info  		C154(0.00); C188(0.00); C193(0.00); C7(0.00)  LDD0162  [6]
IPM
 Probe Info  		C188(0.00); C193(0.00)  LDD0025  [7]
JW-RF-010
 Probe Info  		C7(0.00); C188(0.00); C193(0.00)  LDD0026  [7]
TFBX
 Probe Info  		C7(0.00); C188(0.00); C206(0.00); C193(0.00)  LDD0027  [7]
WYneN
 Probe Info  		N.A.  LDD0021  [8]
Acrolein
 Probe Info  		H14(0.00); H170(0.00)  LDD0217  [9]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [9]
Methacrolein
 Probe Info  		C188(0.00); C193(0.00)  LDD0218  [9]
W1
 Probe Info  		C193(0.00); C188(0.00); D12(0.00); Y24(0.00)  LDD0236  [10]
NAIA_5
 Probe Info  		C145(0.00); C242(0.00); C206(0.00); C7(0.00)  LDD2223  [11]
HHS-465
 Probe Info  		N.A.  LDD2240  [12]
HHS-475
 Probe Info  		Y110(0.70); Y114(1.61); Y184(1.43); Y196(1.27)  LDD2238  [13]
HHS-482
 Probe Info  		Y110(1.46); Y114(1.53); Y184(1.02); Y196(0.85)  LDD2239  [13]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info  		3.89  LDD0136  [14]
STS-2
 Probe Info  		6.44  LDD0138  [14]
AEA-DA
 Probe Info  		9.20  LDD0146  [15]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa H14(0.00); H170(0.00); H90(0.00)  LDD0222  [9]
 LDCM0082  FK866 A-549 9.20  LDD0146  [15]
 LDCM0107  IAA HeLa H14(0.00); H170(0.00); H90(0.00)  LDD0221  [9]
 LDCM0022  KB02 22RV1 C242(0.67)  LDD2243  [2]
 LDCM0023  KB03 22RV1 C242(0.68)  LDD2660  [2]
 LDCM0024  KB05 HMCB C242(0.85)  LDD3312  [2]
 LDCM0109  NEM HeLa H14(0.00); H90(0.00); H170(0.00)  LDD0223  [9]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C188(1.02)  LDD2093  [3]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C193(0.95)  LDD2119  [3]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C188(0.90); C193(0.81)  LDD2123  [3]
 LDCM0110  W12 Hep-G2 K201(1.26); K209(2.12); S208(2.12)  LDD0237  [10]
 LDCM0111  W14 Hep-G2 K185(0.73); S208(1.75); K209(1.78); S32(1.78)  LDD0238  [10]
 LDCM0112  W16 Hep-G2 K185(0.98); K179(1.24); N178(1.24); Y184(1.24)  LDD0239  [10]
 LDCM0113  W17 Hep-G2 K185(0.60); Y184(0.60); K209(1.24); S208(1.24)  LDD0240  [10]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 9 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Chenodeoxycholic Acid Small molecular drug DB06777
Fenofibrate Small molecular drug DB01039
Lumateperone Small molecular drug DB06077
Methylprednisolone Small molecular drug DB00959
Nabumetone Small molecular drug DB00461
Nadh Small molecular drug DB00157
Ursodeoxycholic Acid Small molecular drug DB01586
Glycyrrhizic Acid . DB13751
Ozanimod . DB12612
Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Epitestosterone . DB07768
Nicotinamide Adenine Dinucleotide Phosphate . DB03461

References

1 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
2 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
3 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
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 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
6 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
7 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
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 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.
10 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.
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 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
15 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.