Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRT5P5I)

• DOT Name: Ceramide glucosyltransferase
• Synonyms: EC 2.4.1.80; GLCT-1; Glucosylceramide synthase; GCS; Glycosylceramide synthase; UDP-glucose ceramide glucosyltransferase; UDP-glucose:N-acylsphingosine D-glucosyltransferase
• Gene Name: UGCG
• Related Disease: Non-syndromic ichthyosis
• UniProt ID: CEGT_HUMAN
• EC Number: 2.4.1.80
• Pfam ID: PF13506
• Sequence:
  MALLDLALEGMAVFGFVLFLVLWLMHFMAIIYTRLHLNKKATDKQPYSKLPGVSLLKPLK
  GVDPNLINNLETFFELDYPKYEVLLCVQDHDDPAIDVCKKLLGKYPNVDARLFIGGKKVG
  INPKINNLMPGYEVAKYDLIWICDSGIRVIPDTLTDMVNQMTEKVGLVHGLPYVADRQGF
  AATLEQVYFGTSHPRYYISANVTGFKCVTGMSCLMRKDVLDQAGGLIAFAQYIAEDYFMA
  KAIADRGWRFAMSTQVAMQNSGSYSISQFQSRMIRWTKLRINMLPATIICEPISECFVAS
  LIIGWAAHHVFRWDIMVFFMCHCLAWFIFDYIQLRGVQGGTLCFSKLDYAVAWFIRESMT
  IYIFLSALWDPTISWRTGRYRLRCGGTAEEILDV
• Function: Participates in the initial step of the glucosylceramide-based glycosphingolipid/GSL synthetic pathway at the cytosolic surface of the Golgi. Catalyzes the transfer of glucose from UDP-glucose to ceramide to produce glucosylceramide/GlcCer (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine). GlcCer is the core component of glycosphingolipids/GSLs, amphipathic molecules consisting of a ceramide lipid moiety embedded in the outer leaflet of the membrane, linked to one of hundreds of different externally oriented oligosaccharide structures. Glycosphingolipids are essential components of membrane microdomains that mediate membrane trafficking and signal transduction, implicated in many fundamental cellular processes, including growth, differentiation, migration, morphogenesis, cell-to-cell and cell-to-matrix interactions. They are required for instance in the proper development and functioning of the nervous system. As an example of their role in signal transduction, they regulate the leptin receptor/LEPR in the leptin-mediated signaling pathway. They also play an important role in the establishment of the skin barrier regulating keratinocyte differentiation and the proper assembly of the cornified envelope. The biosynthesis of GSLs is also required for the proper intestinal endocytic uptake of nutritional lipids. Catalyzes the synthesis of xylosylceramide/XylCer (such as beta-D-xylosyl-(1<->1')-N-acylsphing-4-enine) using UDP-Xyl as xylose donor.
• Tissue Specificity: Found in all tissues examined.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glycosphingolipid biosynthesis (R-HSA-9840309)
• BioCyc Pathway: MetaCyc:HS07494-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-syndromic ichthyosis	DISZ9QBQ	Limited	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Ceramide glucosyltransferase affects the response to substance of Methotrexate.	[30]

35 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ceramide glucosyltransferase.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ceramide glucosyltransferase.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Ceramide glucosyltransferase.	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ceramide glucosyltransferase.	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ceramide glucosyltransferase.	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ceramide glucosyltransferase.	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ceramide glucosyltransferase.	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ceramide glucosyltransferase.	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ceramide glucosyltransferase.	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ceramide glucosyltransferase.	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ceramide glucosyltransferase.	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ceramide glucosyltransferase.	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Ceramide glucosyltransferase.	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ceramide glucosyltransferase.	[14]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Ceramide glucosyltransferase.	[15]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Ceramide glucosyltransferase.	[16]
Bleomycin	DMNER5S	Approved	Bleomycin decreases the expression of Ceramide glucosyltransferase.	[17]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Ceramide glucosyltransferase.	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ceramide glucosyltransferase.	[19]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Ceramide glucosyltransferase.	[20]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Ceramide glucosyltransferase.	[4]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Ceramide glucosyltransferase.	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ceramide glucosyltransferase.	[11]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 increases the expression of Ceramide glucosyltransferase.	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ceramide glucosyltransferase.	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ceramide glucosyltransferase.	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ceramide glucosyltransferase.	[24]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Ceramide glucosyltransferase.	[25]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Ceramide glucosyltransferase.	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ceramide glucosyltransferase.	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ceramide glucosyltransferase.	[25]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Ceramide glucosyltransferase.	[27]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Ceramide glucosyltransferase.	[28]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Ceramide glucosyltransferase.	[29]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Ceramide glucosyltransferase.	[17]

References

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