Details of the Target

General Information of Target

Target ID LDTP01767
Target Name Aldehyde dehydrogenase 1A1 (ALDH1A1)
Gene Name ALDH1A1
Gene ID 216
Synonyms
ALDC; ALDH1; PUMB1; Aldehyde dehydrogenase 1A1; EC 1.2.1.19; EC 1.2.1.28; EC 1.2.1.3; EC 1.2.1.36; 3-deoxyglucosone dehydrogenase; ALDH-E1; ALHDII; Aldehyde dehydrogenase family 1 member A1; Aldehyde dehydrogenase, cytosolic; Retinal dehydrogenase 1; RALDH 1; RalDH1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSSSGTPDLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKEDV
DKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMESMNGGKLYSNAYL
NDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHEPIGVCGQIIPWNFPLVMLIWKI
GPALSCGNTVVVKPAEQTPLTALHVASLIKEAGFPPGVVNIVPGYGPTAGAAISSHMDID
KVAFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQG
QCCIAASRIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDLIES
GKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSLDDVIKR
ANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYGVVSAQCPFGGFKMSGNGRELGE
YGFHEYTEVKTVTVKISQKNS
Target Bioclass
Enzyme
Family
Aldehyde dehydrogenase family
Subcellular location
Cytoplasm, cytosol
Function
Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid . Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid. This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic. Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification. Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins. Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission.
Uniprot ID
P00352
Ensemble ID
ENST00000297785.8
HGNC ID
HGNC:402
ChEMBL ID
CHEMBL3577

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 14 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Alkylaryl probe 3
 Probe Info  		20.00  LDD0381  [1]
W1
 Probe Info  		10.64  LDD0235  [2]
YN-1
 Probe Info  		45.43  LDD0444  [3]
YN-4
 Probe Info  		100.00  LDD0445  [3]
DBIA
 Probe Info  		C370(1.71)  LDD3312  [4]
AZ-9
 Probe Info  		10.00  LDD2154  [5]
IPM
 Probe Info  		C186(14.14); C370(8.82); C133(4.42)  LDD1701  [6]
IA-alkyne
 Probe Info  		C370(0.00); C163(0.00); C186(0.00); C126(0.00)  LDD0162  [7]
BTD
 Probe Info  		C50(0.00); C370(0.00)  LDD0004  [8]
WYneN
 Probe Info  		C133(0.00); C126(0.00); C370(0.00)  LDD0021  [8]
WYneO
 Probe Info  		N.A.  LDD0022  [8]
NHS
 Probe Info  		K412(0.00); K362(0.00)  LDD0010  [8]
HHS-475
 Probe Info  		Y115(1.05); Y119(1.57); Y132(1.27); Y154(0.89)  LDD2238  [9]
HHS-482
 Probe Info  		Y115(0.87); Y119(1.08); Y132(0.80); Y297(1.08)  LDD2239  [9]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
PARPYnD
 Probe Info  		2.03  LDD0374  [10]
FFF probe13
 Probe Info  		5.59  LDD0476  [11]
AEA-DA
 Probe Info  		7.55  LDD0146  [12]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0548  1-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-2-nitroethan-1-one MDA-MB-231 C133(0.66); C186(0.85)  LDD2142  [6]
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C370(0.77); C186(0.86)  LDD2112  [6]
 LDCM0502  1-(Cyanoacetyl)piperidine MDA-MB-231 C370(0.60); C133(0.48)  LDD2095  [6]
 LDCM0537  2-Cyano-N,N-dimethylacetamide MDA-MB-231 C370(0.85)  LDD2130  [6]
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C370(0.54); C133(0.83); C186(0.55); C126(0.75)  LDD2117  [6]
 LDCM0558  2-Cyano-N-phenylacetamide MDA-MB-231 C370(1.34); C186(0.92)  LDD2152  [6]
 LDCM0510  3-(4-(Hydroxydiphenylmethyl)piperidin-1-yl)-3-oxopropanenitrile MDA-MB-231 C370(1.03); C186(0.66)  LDD2103  [6]
 LDCM0539  3-(4-Isopropylpiperazin-1-yl)-3-oxopropanenitrile MDA-MB-231 C370(0.42)  LDD2132  [6]
 LDCM0520  AKOS000195272 MDA-MB-231 C370(0.57); C133(0.70); C186(0.76)  LDD2113  [6]
 LDCM0151  AZ-11 HeLa 10.00  LDD2154  [5]
 LDCM0498  BS-3668 MDA-MB-231 C133(0.85)  LDD2091  [6]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C186(6.99); C133(2.96); C370(2.74)  LDD1702  [6]
 LDCM0082  FK866 A-549 7.55  LDD0146  [12]
 LDCM0022  KB02 697 C370(1.65); C126(1.34); C133(1.64)  LDD2245  [4]
 LDCM0023  KB03 MDA-MB-231 C186(14.14); C370(8.82); C133(4.42)  LDD1701  [6]
 LDCM0024  KB05 HMCB C370(1.71)  LDD3312  [4]
 LDCM0509  N-(4-bromo-3,5-dimethylphenyl)-2-nitroacetamide MDA-MB-231 C370(0.99); C186(0.82)  LDD2102  [6]
 LDCM0528  N-(4-bromophenyl)-2-cyano-N-phenylacetamide MDA-MB-231 C370(0.65)  LDD2121  [6]
 LDCM0496  Nucleophilic fragment 11a MDA-MB-231 C133(1.04)  LDD2089  [6]
 LDCM0497  Nucleophilic fragment 11b MDA-MB-231 C370(1.54); C186(1.12)  LDD2090  [6]
 LDCM0499  Nucleophilic fragment 12b MDA-MB-231 C370(1.07); C133(1.04); C186(1.13)  LDD2092  [6]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C370(1.17); C186(0.54)  LDD2093  [6]
 LDCM0501  Nucleophilic fragment 13b MDA-MB-231 C370(1.14); C133(1.30); C186(0.77)  LDD2094  [6]
 LDCM0504  Nucleophilic fragment 15a MDA-MB-231 C370(0.71); C186(0.90)  LDD2097  [6]
 LDCM0505  Nucleophilic fragment 15b MDA-MB-231 C370(1.09); C133(1.03); C186(0.89)  LDD2098  [6]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C370(1.04); C133(1.41); C186(0.71)  LDD2099  [6]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C370(0.58); C133(0.55); C186(0.80); C50(0.09)  LDD2100  [6]
 LDCM0508  Nucleophilic fragment 17a MDA-MB-231 C370(0.65); C133(0.68)  LDD2101  [6]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C370(0.66); C186(0.65)  LDD2104  [6]
 LDCM0512  Nucleophilic fragment 19a MDA-MB-231 C370(1.37); C133(1.05); C186(0.85)  LDD2105  [6]
 LDCM0513  Nucleophilic fragment 19b MDA-MB-231 C186(0.96)  LDD2106  [6]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C370(0.96); C133(1.26); C186(0.74); C50(1.28)  LDD2107  [6]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C370(0.96); C133(0.85); C186(0.74)  LDD2108  [6]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C370(0.78); C133(0.67); C186(0.85); C126(0.82)  LDD2109  [6]
 LDCM0518  Nucleophilic fragment 22a MDA-MB-231 C370(1.21); C133(1.27); C186(0.86)  LDD2111  [6]
 LDCM0521  Nucleophilic fragment 23b MDA-MB-231 C370(0.61); C186(0.86)  LDD2114  [6]
 LDCM0522  Nucleophilic fragment 24a MDA-MB-231 C370(0.44); C133(0.43); C186(0.53)  LDD2115  [6]
 LDCM0525  Nucleophilic fragment 25b MDA-MB-231 C186(0.90)  LDD2118  [6]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C370(2.18); C133(0.81); C186(1.45)  LDD2119  [6]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C370(1.03)  LDD2120  [6]
 LDCM0529  Nucleophilic fragment 27b MDA-MB-231 C370(0.56); C186(0.86)  LDD2122  [6]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C370(0.98); C133(0.99); C186(0.88); C50(1.25)  LDD2123  [6]
 LDCM0531  Nucleophilic fragment 28b MDA-MB-231 C370(0.14); C133(0.31)  LDD2124  [6]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C370(0.82); C133(1.02); C186(0.59); C126(0.97)  LDD2125  [6]
 LDCM0533  Nucleophilic fragment 29b MDA-MB-231 C370(0.12); C133(0.37); C186(1.02)  LDD2126  [6]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C370(0.60); C133(0.83); C186(0.53); C50(1.05)  LDD2127  [6]
 LDCM0536  Nucleophilic fragment 31 MDA-MB-231 C370(1.19); C133(1.04)  LDD2129  [6]
 LDCM0540  Nucleophilic fragment 35 MDA-MB-231 C370(0.50)  LDD2133  [6]
 LDCM0541  Nucleophilic fragment 36 MDA-MB-231 C370(0.46)  LDD2134  [6]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C370(1.43); C186(1.09); C50(1.37)  LDD2135  [6]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C370(1.32); C133(1.66); C186(0.81); C126(1.31)  LDD2136  [6]
 LDCM0544  Nucleophilic fragment 39 MDA-MB-231 C370(1.01); C133(1.07); C186(0.81); C126(1.06)  LDD2137  [6]
 LDCM0211  Nucleophilic fragment 3b MDA-MB-231 C370(2.25); C186(1.55)  LDD1700  [6]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C370(0.87); C133(1.22); C186(0.52)  LDD2140  [6]
 LDCM0547  Nucleophilic fragment 41 MDA-MB-231 C370(0.56); C186(0.57)  LDD2141  [6]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C370(3.34); C133(1.18); C186(1.85)  LDD2144  [6]
 LDCM0551  Nucleophilic fragment 5b MDA-MB-231 C370(0.92); C186(0.70)  LDD2145  [6]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C370(0.97); C133(1.21); C186(0.67)  LDD2146  [6]
 LDCM0554  Nucleophilic fragment 7a MDA-MB-231 C370(0.49); C133(0.39); C186(0.42)  LDD2148  [6]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C370(0.63)  LDD2150  [6]
 LDCM0559  Nucleophilic fragment 9b MDA-MB-231 C186(1.44)  LDD2153  [6]
 LDCM0112  W16 Hep-G2 K398(1.38)  LDD0239  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Dopamine beta-hydroxylase (DBH) Copper type II ascorbate-dependent monooxygenase family P09172
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Junctophilin-3 (JPH3) Junctophilin family Q8WXH2
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Glial fibrillary acidic protein (GFAP) Intermediate filament family P14136

The Drug(s) Related To This Target

Approved
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Nadh Small molecular drug DB00157
Tretinoin Small molecular drug DB00755
Vitamin A Small molecular drug DB00162
Glycerin . DB09462
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
14-dithiothreitol Small molecular drug DB04447

References

1 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
2 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.
3 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
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 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
6 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
7 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
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 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.
10 Structure-Guided Design and In-Cell Target Profiling of a Cell-Active Target Engagement Probe for PARP Inhibitors. ACS Chem Biol. 2020 Feb 21;15(2):325-333. doi: 10.1021/acschembio.9b00963. Epub 2020 Feb 10.
11 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
12 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.