Details of Drug Off-Target (DOT)

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

• DOT Name: CMP-sialic acid transporter (SLC35A1)
• Synonyms: CMP-SA-Tr; CMP-Sia-Tr; CST; Solute carrier family 35 member A1
• Gene Name: SLC35A1
• Related Disease:
  SLC35A1-congenital disorder of glycosylation
  SRD5A3-congenital disorder of glycosylation
• UniProt ID: S35A1_HUMAN
• Pfam ID: PF04142
• Sequence:
  MAAPRDNVTLLFKLYCLAVMTLMAAVYTIALRYTRTSDKELYFSTTAVCITEVIKLLLSV
  GILAKETGSLGRFKASLRENVLGSPKELLKLSVPSLVYAVQNNMAFLALSNLDAAVYQVT
  YQLKIPCTALCTVLMLNRTLSKLQWVSVFMLCAGVTLVQWKPAQATKVVVEQNPLLGFGA
  IAIAVLCSGFAGVYFEKVLKSSDTSLWVRNIQMYLSGIIVTLAGVYLSDGAEIKEKGFFY
  GYTYYVWFVIFLASVGGLYTSVVVKYTDNIMKGFSAAAAIVLSTIASVMLFGLQITLTFA
  LGTLLVCVSIYLYGLPRQDTTSIQQGETASKERVIGV
• Function: Transports CMP-sialic acid from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges CMP-sialic acid for CMP. Binds both CMP-sialic acid and free CMP, but has higher affinity for free CMP. Also able to exchange CMP-sialic acid for AMP and UMP. Also mediates the transport of CDP-ribitol.
• Reactome Pathway:
  Defective SLC35A1 causes congenital disorder of glycosylation 2F (CDG2F) (R-HSA-5619037)
  Defective SLC35A1 causes congenital disorder of glycosylation 2F (CDG2F) (R-HSA-5663020)
  Transport of nucleotide sugars (R-HSA-727802)
  Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
SLC35A1-congenital disorder of glycosylation	DISH0T2X	Strong	Autosomal recessive	[1]
SRD5A3-congenital disorder of glycosylation	DISGHPPC	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of CMP-sialic acid transporter (SLC35A1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CMP-sialic acid transporter (SLC35A1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CMP-sialic acid transporter (SLC35A1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CMP-sialic acid transporter (SLC35A1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of CMP-sialic acid transporter (SLC35A1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CMP-sialic acid transporter (SLC35A1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of CMP-sialic acid transporter (SLC35A1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of CMP-sialic acid transporter (SLC35A1).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of CMP-sialic acid transporter (SLC35A1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CMP-sialic acid transporter (SLC35A1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of CMP-sialic acid transporter (SLC35A1).	[11]

References

• [1] Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter. Blood. 2005 Apr 1;105(7):2671-6. doi: 10.1182/blood-2004-09-3509. Epub 2004 Dec 2.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.