Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT54EM29)

• DOT Name: Regulatory solute carrier protein family 1 member 1 (RSC1A1)
• Synonyms: Transporter regulator RS1; hRS1
• Gene Name: RSC1A1
• Related Disease:
  Chronic kidney disease
  Dentatorubral-pallidoluysian atrophy
  Liver cirrhosis
  Nephropathy
  Obesity
• UniProt ID: RSCA1_HUMAN
• Sequence:
  MSSLPTSDGFNHPARSSGQSPDVGNPMSLARSVSASVCPIKPSDSDRIEPKAVKALKASA
  EFQLNSEKKEHLSLQDLSDHASSADHAPTDQSPAMPMQNSSEEITVAGNLEKSAERSTQG
  LKFHLHTRQEASLSVTSTRMHEPQMFLGEKDWHPENQNLSQVSDPQQHEEPGNEQYEVAQ
  QKASHDQEYLCNIGDLELPEERQQNQHKIVDLEATMKGNGLPQNVDPPSAKKSIPSSECS
  GCSNSETFMEIDTAQQSLVTLLNSTGRQNANVKNIGALDLTLDNPLMEVETSKCNPSSEI
  LNDSISTQDLQPPETNVEIPGTNKEYGHYSSPSLCGSCQPSVESAEESCPSITAALKELH
  ELLVVSSKPASENTSEEVICQSETIAEGQTSIKDLSERWTQNEHLTQNEQCPQVSFHQAI
  SVSVETEKLTGTSSDTGREAVENVNFRSLGDGLSTDKEGVPKSRESINKNRSVTVTSAKT
  SNQLHCTLGVEISPKLLAGEEDALNQTSEQTKSLSSNFILVKDLGQGIQNSVTDRPETRE
  NVCPDASRPLLEYEPPTSHPSSSPAILPPLIFPATDIDRILRAGFTLQEALGALHRVGGN
  ADLALLVLLAKNIVVPT
• Function: Mediates transcriptional and post-transcriptional regulation of SLC5A1. Inhibits a dynamin and PKC-dependent exocytotic pathway of SLC5A1. Also involved in transcriptional regulation of SLC22A2. Exhibits glucose-dependent, short-term inhibition of SLC5A1 and SLC22A2 by inhibiting the release of vesicles from the trans-Golgi network.
• Tissue Specificity: Expressed in small intestine, kidney and brain.
• Reactome Pathway:
  Intestinal hexose absorption (R-HSA-8981373)
  Organic cation transport (R-HSA-549127)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Strong	Biomarker	[1]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Biomarker	[2]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[3]
Nephropathy	DISXWP4P	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Regulatory solute carrier protein family 1 member 1 (RSC1A1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Regulatory solute carrier protein family 1 member 1 (RSC1A1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Regulatory solute carrier protein family 1 member 1 (RSC1A1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Regulatory solute carrier protein family 1 member 1 (RSC1A1).	[8]

References

• [1] News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document.J Hepatol. 2019 Oct;71(4):811-822. doi: 10.1016/j.jhep.2019.07.002. Epub 2019 Jul 11.
• [2] Terlipressin for the treatment of hepatorenal syndrome: an overview of current evidence.Curr Med Res Opin. 2019 May;35(5):859-868. doi: 10.1080/03007995.2018.1552575. Epub 2019 Jan 4.
• [3] Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis.Nat Rev Nephrol. 2020 Mar;16(3):137-155. doi: 10.1038/s41581-019-0218-4. Epub 2019 Nov 13.
• [4] Mice without the regulator gene Rsc1A1 exhibit increased Na+-D-glucose cotransport in small intestine and develop obesity.Mol Cell Biol. 2005 Jan;25(1):78-87. doi: 10.1128/MCB.25.1.78-87.2005.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.