Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWBV9CR)

• DOT Name: Sodium-independent sulfate anion transporter (SLC26A11)
• Synonyms: Solute carrier family 26 member 11
• Gene Name: SLC26A11
• Related Disease:
  Deafness
  Mucopolysaccharidosis type 3A
• UniProt ID: S2611_HUMAN
• Pfam ID: PF01740 ; PF00916
• Sequence:
  MPSSVTALGQARSSGPGMAPSACCCSPAALQRRLPILAWLPSYSLQWLKMDFVAGLSVGL
  TAIPQALAYAEVAGLPPQYGLYSAFMGCFVYFFLGTSRDVTLGPTAIMSLLVSFYTFHEP
  AYAVLLAFLSGCIQLAMGVLRLGFLLDFISYPVIKGFTSAAAVTIGFGQIKNLLGLQNIP
  RPFFLQVYHTFLRIAETRVGDAVLGLVCMLLLLVLKLMRDHVPPVHPEMPPGVRLSRGLV
  WAATTARNALVVSFAALVAYSFEVTGYQPFILTGETAEGLPPVRIPPFSVTTANGTISFT
  EMVQDMGAGLAVVPLMGLLESIAVAKAFASQNNYRIDANQELLAIGLTNMLGSLVSSYPV
  TGSFGRTAVNAQSGVCTPAGGLVTGVLVLLSLDYLTSLFYYIPKSALAAVIIMAVAPLFD
  TKIFRTLWRVKRLDLLPLCVTFLLCFWEVQYGILAGALVSLLMLLHSAARPETKVSEGPV
  LVLQPASGLSFPAMEALREEILSRALEVSPPRCLVLECTHVCSIDYTVVLGLGELLQDFQ
  KQGVALAFVGLQVPVLRVLLSADLKGFQYFSTLEEAEKHLRQEPGTQPYNIREDSILDQK
  VALLKA
• Function: Sodium-independent anion exchanger mediating bicarbonate, chloride, sulfate and oxalate transport. Exhibits sodium-independent sulfate anion transporter activity that may cooperate with SLC26A2 to mediate DIDS-sensitive sulfate uptake into high endothelial venules endothelial cells (HEVEC). In the kidney, mediates chloride-bicarbonate exchange, facilitating V-ATPase-mediated acid secretion. May function as a chloride channel, playing an important role in moderating chloride homeostasis and neuronal activity in the cerebellum.
• Tissue Specificity: Detected in all tissues tested with highest expression observed in brain, kidney, HEVEC and placenta and lowest in pancreas, skeletal muscle, liver, lung and heart.
• Reactome Pathway: Multifunctional anion exchangers (R-HSA-427601)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Deafness	DISKCLH4	Strong	Genetic Variation	[1]
Mucopolysaccharidosis type 3A	DIS2TLNF	Strong	Genetic Variation	[2]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Sodium-independent sulfate anion transporter (SLC26A11) affects the uptake of 3-iodothyronamine.	[15]

11 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 Sodium-independent sulfate anion transporter (SLC26A11).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[10]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[11]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[12]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sodium-independent sulfate anion transporter (SLC26A11).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium-independent sulfate anion transporter (SLC26A11).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium-independent sulfate anion transporter (SLC26A11).	[13]

References

• [1] Molecular and functional characterization of SLC26A11, a sodium-independent sulfate transporter from high endothelial venules.FASEB J. 2003 May;17(8):890-2. doi: 10.1096/fj.02-0787fje. Epub 2003 Mar 5.
• [2] Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA.Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1321-35. doi: 10.1107/S1399004714002739. Epub 2014 Apr 30.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [11] 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.
• [12] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.