Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG192UT)

• DOT Name: Solute carrier family 22 member 16 (SLC22A16)
• Synonyms: Carnitine transporter 2; CT2; Fly-like putative transporter 2; FLIPT2; Flipt 2; Organic cation transporter OKB1; Organic cation/carnitine transporter 6
• Gene Name: SLC22A16
• UniProt ID: S22AG_HUMAN
• Pfam ID: PF00083
• Sequence:
  MGSRHFEGIYDHVGHFGRFQRVLYFICAFQNISCGIHYLASVFMGVTPHHVCRPPGNVSQ
  VVFHNHSNWSLEDTGALLSSGQKDYVTVQLQNGEIWELSRCSRNKRENTSSLGYEYTGSK
  KEFPCVDGYIYDQNTWKSTAVTQWNLVCDRKWLAMLIQPLFMFGVLLGSVTFGYFSDRLG
  RRVVLWATSSSMFLFGIAAAFAVDYYTFMAARFFLAMVASGYLVVGFVYVMEFIGMKSRT
  WASVHLHSFFAVGTLLVALTGYLVRTWWLYQMILSTVTVPFILCCWVLPETPFWLLSEGR
  YEEAQKIVDIMAKWNRASSCKLSELLSLDLQGPVSNSPTEVQKHNLSYLFYNWSITKRTL
  TVWLIWFTGSLGFYSFSLNSVNLGGNEYLNLFLLGVVEIPAYTFVCIAMDKVGRRTVLAY
  SLFCSALACGVVMVIPQKHYILGVVTAMVGKFAIGAAFGLIYLYTAELYPTIVRSLAVGS
  GSMVCRLASILAPFSVDLSSIWIFIPQLFVGTMALLSGVLTLKLPETLGKRLATTWEEAA
  KLESENESKSSKLLLTTNNSGLEKTEAITPRDSGLGE
• Function: Facilitative organic cation transporter that mediates the transport of carnitine as well as the polyamine spermidine. Mediates the partially Na(+)-dependent bidirectional transport of carnitine. May mediate L-carnitine secretion from testis epididymal epithelium into the lumen which is involved in the maturation of spermatozoa.
• Tissue Specificity: Expressed in testis and epididymis (at protein level) . Expressed in endometrium (at protein level); highly expressed during the normal secretory phase, but expression is significantly reduced in the proliferative phase . Expressed at lower levels in adult tissues including bone marrow (at protein level) . Expressed in hematopoietic cells, including CD34(+) leukocytes . Expressed in fetal liver (at protein level), brain, lung, kidney, heart, skeletal muscle, spleen and thymus . Expressed in leukemia cells . Abundantly expressed in ovarian cancer clear-cell adenocarcinoma .
• Reactome Pathway: Organic cation transport (R-HSA-549127)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Solute carrier family 22 member 16 (SLC22A16) increases the uptake of Doxorubicin.	[5]
[14C]TEA	DM6SFYH	Investigative	Solute carrier family 22 member 16 (SLC22A16) increases the uptake of [14C]TEA.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Solute carrier family 22 member 16 (SLC22A16).	[1]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Solute carrier family 22 member 16 (SLC22A16).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 22 member 16 (SLC22A16).	[4]

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 increases the methylation of Solute carrier family 22 member 16 (SLC22A16).	[3]

References

• [1] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [2] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [5] Characterization of the organic cation transporter SLC22A16: a doxorubicin importer. Biochem Biophys Res Commun. 2005 Aug 5;333(3):754-62. doi: 10.1016/j.bbrc.2005.05.174.