Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWKN3Z7)

• DOT Name: Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2)
• Synonyms: PAPS transporter 1; Putative MAPK-activating protein PM15; Putative NF-kappa-B-activating protein 48; Solute carrier family 35 member B2
• Gene Name: SLC35B2
• Related Disease: Leukodystrophy, hypomyelinating, 26, with chondrodysplasia
• UniProt ID: S35B2_HUMAN
• Pfam ID: PF08449
• Sequence:
  MDARWWAVVVLAAFPSLGAGGETPEAPPESWTQLWFFRFVVNAAGYASFMVPGYLLVQYF
  RRKNYLETGRGLCFPLVKACVFGNEPKASDEVPLAPRTEAAETTPMWQALKLLFCATGLQ
  VSYLTWGVLQERVMTRSYGATATSPGERFTDSQFLVLMNRVLALIVAGLSCVLCKQPRHG
  APMYRYSFASLSNVLSSWCQYEALKFVSFPTQVLAKASKVIPVMLMGKLVSRRSYEHWEY
  LTATLISIGVSMFLLSSGPEPRSSPATTLSGLILLAGYIAFDSFTSNWQDALFAYKMSSV
  QMMFGVNFFSCLFTVGSLLEQGALLEGTRFMGRHSEFAAHALLLSICSACGQLFIFYTIG
  QFGAAVFTIIMTLRQAFAILLSCLLYGHTVTVVGGLGVAVVFAALLLRVYARGRLKQRGK
  KAVPVESPVQKV
• Function: Probably functions as a 3'-phosphoadenylyl sulfate:adenosine 3',5'-bisphosphate antiporter at the Golgi membranes. Mediates the transport from the cytosol into the lumen of the Golgi of 3'-phosphoadenylyl sulfate/adenosine 3'-phospho 5'-phosphosulfate (PAPS), a universal sulfuryl donor for sulfation events that take place in that compartment.
• Tissue Specificity: Highly expressed in the placenta, pancreas, mammary gland and skeletal muscle. Weakly or not expressed in colon, heart and prostate . Expressed in the brain, predominantly in frontal lobe gray matter, subcortical frontal white matter and cerebellum .
• Reactome Pathway:
  Transport of nucleotide sugars (R-HSA-727802)
  Transport and synthesis of PAPS (R-HSA-174362)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukodystrophy, hypomyelinating, 26, with chondrodysplasia	DISQ6M2O	Limited	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[10]

2 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 Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Adenosine 3'-phospho 5'-phosphosulfate transporter 1 (SLC35B2).	[9]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] 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.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.