Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium-dependent phosphate transport protein 4 (SLC17A3)
• Synonyms: Na(+)/PI cotransporter 4; NPT4; Sodium/phosphate cotransporter 4; Solute carrier family 17 member 3
• Gene Name: SLC17A3
• UniProt ID: NPT4_HUMAN
• Pfam ID: PF07690
• Sequence:
  MATKTELSPTARESKNAQDMQVDETLIPRKVPSLCSARYGIALVLHFCNFTTIAQNVIMN
  ITMVAMVNSTSPQSQLNDSSEVLPVDSFGGLSKAPKSLPAKSSILGGQFAIWEKWGPPQE
  RSRLCSIALSGMLLGCFTAILIGGFISETLGWPFVFYIFGGVGCVCCLLWFVVIYDDPVS
  YPWISTSEKEYIISSLKQQVGSSKQPLPIKAMLRSLPIWSICLGCFSHQWLVSTMVVYIP
  TYISSVYHVNIRDNGLLSALPFIVAWVIGMVGGYLADFLLTKKFRLITVRKIATILGSLP
  SSALIVSLPYLNSGYITATALLTLSCGLSTLCQSGIYINVLDIAPRYSSFLMGASRGFSS
  IAPVIVPTVSGFLLSQDPEFGWRNVFFLLFAVNLLGLLFYLIFGEADVQEWAKERKLTRL
• Function: [Isoform 2]: Transports organic anions in a voltage-driven, multispecific, manner, on the apical side of renal proximal tubule. In particular, participates in the secretion of urate from the cell into the lumen. Urate is the end product of purine metabolism. May have roles in the metabolism and secretion of estrone sulfate, estradiol-17-beta-glucuronide, ochratoxin A, as wells as drugs such as bumetanide.
• Tissue Specificity: Expressed in the liver and kidney . It is detected in proximal tubules in renal cortex as well as some tubules and glomeruli, with highest expression at the apical side of proximal tubules (at protein level) .
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Bumetanide	DMRV7H0	Approved	Sodium-dependent phosphate transport protein 4 (SLC17A3) affects the transport of Bumetanide.	[5]
Aminohippuric acid	DMUN54G	Investigative	Sodium-dependent phosphate transport protein 4 (SLC17A3) affects the transport of Aminohippuric acid.	[5]
Uric acid	DMA1MKT	Investigative	Sodium-dependent phosphate transport protein 4 (SLC17A3) affects the transport of Uric acid.	[5]
[3H]estrone-3-sulphate	DMGPF0N	Investigative	Sodium-dependent phosphate transport protein 4 (SLC17A3) affects the transport of [3H]estrone-3-sulphate.	[5]

2 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 Sodium-dependent phosphate transport protein 4 (SLC17A3).	[1]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Sodium-dependent phosphate transport protein 4 (SLC17A3).	[2]

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 Sodium-dependent phosphate transport protein 4 (SLC17A3).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Sodium-dependent phosphate transport protein 4 (SLC17A3).	[4]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [3] 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.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms. J Pharmacol Sci. 2011;115(2):249-53. doi: 10.1254/jphs.10228sc. Epub 2011 Jan 26.