Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBDPI8I)

• DOT Name: Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3)
• Synonyms: 3'-phosphoadenosine 5'-phosphosulfate transporter; PAPS transporter 2; Solute carrier family 35 member B3
• Gene Name: SLC35B3
• UniProt ID: S35B3_HUMAN
• Pfam ID: PF08449
• Sequence:
  MDLTQQAKDIQNITVQETNKNNSESIECSKITMDLKFNNSRKYISITVPSKTQTMSPHIK
  SVDDVVVLGMNLSKFNKLTQFFICVAGVFVFYLIYGYLQELIFSVEGFKSCGWYLTLVQF
  AFYSIFGLIELQLIQDKRRRIPGKTYMIIAFLTVGTMGLSNTSLGYLNYPTQVIFKCCKL
  IPVMLGGVFIQGKRYNVADVSAAICMSLGLIWFTLADSTTAPNFNLTGVVLISLALCADA
  VIGNVQEKAMKLHNASNSEMVLYSYSIGFVYILLGLTCTSGLGPAVTFCAKNPVRTYGYA
  FLFSLTGYFGISFVLALIKIFGALIAVTVTTGRKAMTIVLSFIFFAKPFTFQYVWSGLLV
  VLGIFLNVYSKNMDKIRLPSLYDLINKSVEARKSRTLAQTV
• 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: Preferentially and highly expressed in colon.
• Reactome Pathway:
  Transport of nucleotide sugars (R-HSA-727802)
  Transport and synthesis of PAPS (R-HSA-174362)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[4]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[8]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[9]

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 decreases the methylation of Adenosine 3'-phospho 5'-phosphosulfate transporter 2 (SLC35B3).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [6] 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.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] 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.