General Information of Target

Target ID LDTP05905
Target Name Acid ceramidase (ASAH1)
Gene Name ASAH1
Gene ID 427
Synonyms
ASAH; Acid ceramidase; AC; ACDase; Acid CDase; EC 3.5.1.23; Acylsphingosine deacylase; N-acylethanolamine hydrolase ASAH1; EC 3.5.1.-; N-acylsphingosine amidohydrolase; Putative 32 kDa heart protein; PHP32) [Cleaved into: Acid ceramidase subunit alpha; Acid ceramidase subunit beta]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPGRSCVALVLLAAAVSCAVAQHAPPWTEDCRKSTYPPSGPTYRGAVPWYTINLDLPPYK
RWHELMLDKAPVLKVIVNSLKNMINTFVPSGKIMQVVDEKLPGLLGNFPGPFEEEMKGIA
AVTDIPLGEIISFNIFYELFTICTSIVAEDKKGHLIHGRNMDFGVFLGWNINNDTWVITE
QLKPLTVNLDFQRNNKTVFKASSFAGYVGMLTGFKPGLFSLTLNERFSINGGYLGILEWI
LGKKDVMWIGFLTRTVLENSTSYEEAKNLLTKTKILAPAYFILGGNQSGEGCVITRDRKE
SLDVYELDAKQGRWYVVQTNYDRWKHPFFLDDRRTPAKMCLNRTSQENISFETMYDVLST
KPVLNKLTVYTTLIDVTKGQFETYLRDCPDPCIGW
Target Bioclass
Enzyme
Family
Acid ceramidase family
Subcellular location
Lysosome; Nucleus
Function
Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. Has a higher catalytic efficiency towards C12-ceramides versus other ceramides. Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine. For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used. Has also an N-acylethanolamine hydrolase activity. By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes. Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis. By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis.; [Isoform 2]: May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity.
Uniprot ID
Q13510
Ensemble ID
ENST00000314146.10
HGNC ID
HGNC:735
ChEMBL ID
CHEMBL5463

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
IM95 SNV: p.L54P .
OAW28 SNV: p.P2S .
OCUM1 SNV: p.T222A .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Alkylaryl probe 1
 Probe Info 
20.00  LDD0387  [1]
Alkylaryl probe 2
 Probe Info 
20.00  LDD0391  [1]
FBPP2
 Probe Info 
152.19  LDD0318  [2]
FBP2
 Probe Info 
2.63  LDD0317  [2]
YN-1
 Probe Info 
100.00  LDD0444  [3]
STPyne
 Probe Info 
K152(5.56); K325(9.07)  LDD0277  [4]
Alkylaryl probe 3
 Probe Info 
3.82  LDD0384  [1]
Jackson_14
 Probe Info 
2.38  LDD0123  [5]
IPM
 Probe Info 
N.A.  LDD2156  [6]
PAL-AfBPP Probe
Click To Hide/Show 126 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C004
 Probe Info 
5.82  LDD1714  [7]
C010
 Probe Info 
5.17  LDD1719  [7]
C022
 Probe Info 
24.93  LDD1728  [7]
C026
 Probe Info 
5.54  LDD1732  [7]
C040
 Probe Info 
13.45  LDD1740  [7]
C041
 Probe Info 
16.56  LDD1741  [7]
C045
 Probe Info 
5.78  LDD1744  [7]
C056
 Probe Info 
16.91  LDD1753  [7]
C063
 Probe Info 
13.83  LDD1760  [7]
C067
 Probe Info 
6.41  LDD1763  [7]
C070
 Probe Info 
29.45  LDD1766  [7]
C072
 Probe Info 
11.47  LDD1768  [7]
C082
 Probe Info 
5.24  LDD1774  [7]
C085
 Probe Info 
5.28  LDD1777  [7]
C087
 Probe Info 
11.00  LDD1779  [7]
C091
 Probe Info 
24.59  LDD1782  [7]
C092
 Probe Info 
36.00  LDD1783  [7]
C094
 Probe Info 
27.67  LDD1785  [7]
C106
 Probe Info 
52.35  LDD1793  [7]
C107
 Probe Info 
17.63  LDD1794  [7]
C108
 Probe Info 
25.46  LDD1795  [7]
C112
 Probe Info 
53.08  LDD1799  [7]
C129
 Probe Info 
8.00  LDD1811  [7]
C130
 Probe Info 
8.75  LDD1812  [7]
C134
 Probe Info 
32.22  LDD1816  [7]
C135
 Probe Info 
10.63  LDD1817  [7]
C139
 Probe Info 
11.39  LDD1821  [7]
C140
 Probe Info 
18.38  LDD1822  [7]
C141
 Probe Info 
25.46  LDD1823  [7]
C143
 Probe Info 
26.91  LDD1825  [7]
C149
 Probe Info 
5.94  LDD1830  [7]
C153
 Probe Info 
39.67  LDD1834  [7]
C159
 Probe Info 
23.92  LDD1839  [7]
C160
 Probe Info 
8.82  LDD1840  [7]
C161
 Probe Info 
25.28  LDD1841  [7]
C163
 Probe Info 
19.16  LDD1843  [7]
C165
 Probe Info 
19.97  LDD1845  [7]
C170
 Probe Info 
30.91  LDD1850  [7]
C171
 Probe Info 
8.51  LDD1851  [7]
C177
 Probe Info 
7.41  LDD1856  [7]
C178
 Probe Info 
27.10  LDD1857  [7]
C183
 Probe Info 
5.31  LDD1861  [7]
C186
 Probe Info 
17.15  LDD1864  [7]
C187
 Probe Info 
69.07  LDD1865  [7]
C194
 Probe Info 
17.39  LDD1870  [7]
C197
 Probe Info 
6.23  LDD1873  [7]
C198
 Probe Info 
18.51  LDD1874  [7]
C201
 Probe Info 
94.35  LDD1877  [7]
C206
 Probe Info 
28.05  LDD1881  [7]
C208
 Probe Info 
6.87  LDD1883  [7]
C211
 Probe Info 
20.11  LDD1885  [7]
C213
 Probe Info 
20.97  LDD1887  [7]
C219
 Probe Info 
11.55  LDD1893  [7]
C220
 Probe Info 
32.45  LDD1894  [7]
C221
 Probe Info 
7.21  LDD1895  [7]
C223
 Probe Info 
9.65  LDD1897  [7]
C225
 Probe Info 
13.18  LDD1898  [7]
C228
 Probe Info 
24.08  LDD1901  [7]
C229
 Probe Info 
9.58  LDD1902  [7]
C231
 Probe Info 
20.39  LDD1904  [7]
C232
 Probe Info 
61.39  LDD1905  [7]
C233
 Probe Info 
18.13  LDD1906  [7]
C235
 Probe Info 
28.25  LDD1908  [7]
C237
 Probe Info 
6.41  LDD1910  [7]
C240
 Probe Info 
17.51  LDD1913  [7]
C243
 Probe Info 
20.25  LDD1916  [7]
C246
 Probe Info 
33.82  LDD1919  [7]
C249
 Probe Info 
21.86  LDD1922  [7]
C264
 Probe Info 
63.56  LDD1935  [7]
C265
 Probe Info 
22.32  LDD1936  [7]
C270
 Probe Info 
13.93  LDD1940  [7]
C273
 Probe Info 
6.15  LDD1943  [7]
C277
 Probe Info 
25.46  LDD1947  [7]
C280
 Probe Info 
15.67  LDD1950  [7]
C281
 Probe Info 
5.54  LDD1951  [7]
C282
 Probe Info 
29.04  LDD1952  [7]
C284
 Probe Info 
27.47  LDD1954  [7]
C287
 Probe Info 
37.79  LDD1957  [7]
C288
 Probe Info 
15.14  LDD1958  [7]
C289
 Probe Info 
30.91  LDD1959  [7]
C293
 Probe Info 
42.81  LDD1963  [7]
C296
 Probe Info 
35.51  LDD1966  [7]
C299
 Probe Info 
7.31  LDD1968  [7]
C302
 Probe Info 
5.31  LDD1971  [7]
C305
 Probe Info 
23.26  LDD1974  [7]
C307
 Probe Info 
8.51  LDD1975  [7]
C310
 Probe Info 
8.94  LDD1977  [7]
C314
 Probe Info 
44.02  LDD1981  [7]
C326
 Probe Info 
16.56  LDD1990  [7]
C339
 Probe Info 
14.12  LDD2002  [7]
C343
 Probe Info 
24.42  LDD2005  [7]
C346
 Probe Info 
14.42  LDD2007  [7]
C348
 Probe Info 
15.89  LDD2009  [7]
C349
 Probe Info 
26.17  LDD2010  [7]
C350
 Probe Info 
69.07  LDD2011  [7]
C355
 Probe Info 
45.89  LDD2016  [7]
C356
 Probe Info 
14.12  LDD2017  [7]
C357
 Probe Info 
8.11  LDD2018  [7]
C362
 Probe Info 
68.12  LDD2023  [7]
C363
 Probe Info 
38.59  LDD2024  [7]
C364
 Probe Info 
31.78  LDD2025  [7]
C376
 Probe Info 
17.63  LDD2036  [7]
C378
 Probe Info 
23.10  LDD2037  [7]
C380
 Probe Info 
7.73  LDD2039  [7]
C383
 Probe Info 
26.35  LDD2042  [7]
C386
 Probe Info 
25.81  LDD2045  [7]
C387
 Probe Info 
7.01  LDD2046  [7]
C388
 Probe Info 
44.63  LDD2047  [7]
C390
 Probe Info 
99.73  LDD2049  [7]
C393
 Probe Info 
5.31  LDD2052  [7]
C399
 Probe Info 
10.63  LDD2058  [7]
C403
 Probe Info 
19.84  LDD2061  [7]
C408
 Probe Info 
5.43  LDD2065  [7]
C413
 Probe Info 
23.92  LDD2069  [7]
C419
 Probe Info 
20.11  LDD2074  [7]
C420
 Probe Info 
29.65  LDD2075  [7]
C425
 Probe Info 
8.46  LDD2080  [7]
C426
 Probe Info 
19.16  LDD2081  [7]
C429
 Probe Info 
16.80  LDD2084  [7]
C431
 Probe Info 
47.18  LDD2086  [7]
FFF probe11
 Probe Info 
20.00  LDD0471  [8]
FFF probe12
 Probe Info 
20.00  LDD0473  [8]
FFF probe13
 Probe Info 
16.73  LDD0475  [8]
FFF probe14
 Probe Info 
20.00  LDD0477  [8]
FFF probe9
 Probe Info 
20.00  LDD0470  [8]
OEA-DA
 Probe Info 
20.00  LDD0046  [9]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0099  Phenelzine MDA-MB-231 3.82  LDD0384  [1]
 LDCM0016  Ranjitkar_cp1 MDA-MB-231 2.38  LDD0123  [5]

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
Beta-secretase 2 (BACE2) Peptidase A1 family Q9Y5Z0
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Steroidogenic factor 1 (NR5A1) Nuclear hormone receptor family Q13285

References

1 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
2 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
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 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
5 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
6 Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics. J Proteome Res. 2022 May 6;21(5):1349-1358. doi: 10.1021/acs.jproteome.2c00174. Epub 2022 Apr 25.
Mass spectrometry data entry: PXD031019
7 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
8 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.
9 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570