Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3RJU3I)

DOT Name	Alkaline ceramidase 1 (ACER1)
Synonyms	AlkCDase 1; Alkaline CDase 1; EC 3.5.1.-; EC 3.5.1.23; Acylsphingosine deacylase 3; N-acylsphingosine amidohydrolase 3
Gene Name	ACER1
Related Disease	Alopecia ( )
UniProt ID	ACER1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.5.1.-; 3.5.1.23
Pfam ID	PF05875
Sequence	MPSIFAYQSSEVDWCESNFQYSELVAEFYNTFSNIPFFIFGPLMMLLMHPYAQKRSRYIY VVWVLFMIIGLFSMYFHMTLSFLGQLLDEIAILWLLGSGYSIWMPRCYFPSFLGGNRSQF IRLVFITTVVSTLLSFLRPTVNAYALNSIALHILYIVCQEYRKTSNKELRHLIEVSVVLW AVALTSWISDRLLCSFWQRIHFFYLHSIWHVLISITFPYGMVTMALVDANYEMPGETLKV RYWPRDSWPVGLPYVEIRGDDKDC
Function	Endoplasmic reticulum ceramidase that catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids at alkaline 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. Exhibits a strong substrate specificity towards the natural stereoisomer of ceramides with D-erythro-sphingosine as a backbone and has a higher activity towards very long-chain unsaturated fatty acids like the C24:1-ceramide. May also hydrolyze dihydroceramides to produce dihydrosphingosine. ACER1 is a skin-specific ceramidase that regulates the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes and more generally plays an important role in skin homeostasis.
Tissue Specificity	Mainly expressed in epidermis.
KEGG Pathway	Sphingolipid metabolism (hsa00600 ) Metabolic pathways (hsa01100 ) Sphingolipid sig.ling pathway (hsa04071 )
Reactome Pathway	Sphingolipid metabolism (R-HSA-428157 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Alopecia	DIS37HU4	Strong	Altered Expression	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alkaline ceramidase 1 (ACER1).	[2]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Alkaline ceramidase 1 (ACER1).	[3]
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References

1	Alkaline Ceramidase 1 Protects Mice from Premature Hair Loss by Maintaining the Homeostasis of Hair Follicle Stem Cells.Stem Cell Reports. 2017 Nov 14;9(5):1488-1500. doi: 10.1016/j.stemcr.2017.09.015. Epub 2017 Oct 19.
2	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
3	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.