Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2WPVXD)

• DOT Name: Large neutral amino acids transporter small subunit 1 (SLC7A5)
• Synonyms: 4F2 light chain; 4F2 LC; 4F2LC; CD98 light chain; Integral membrane protein E16; E16; L-type amino acid transporter 1; hLAT1; Solute carrier family 7 member 5; y+ system cationic amino acid transporter
• Gene Name: SLC7A5
• Related Disease: Complex neurodevelopmental disorder
• UniProt ID: LAT1_HUMAN
• PDB ID: 6IRS; 6IRT; 6JMQ; 7DSK; 7DSL; 7DSN; 7DSQ
• Pfam ID: PF13520
• Sequence:
  MAGAGPKRRALAAPAAEEKEEAREKMLAAKSADGSAPAGEGEGVTLQRNITLLNGVAIIV
  GTIIGSGIFVTPTGVLKEAGSPGLALVVWAACGVFSIVGALCYAELGTTISKSGGDYAYM
  LEVYGSLPAFLKLWIELLIIRPSSQYIVALVFATYLLKPLFPTCPVPEEAAKLVACLCVL
  LLTAVNCYSVKAATRVQDAFAAAKLLALALIILLGFVQIGKGDVSNLDPNFSFEGTKLDV
  GNIVLALYSGLFAYGGWNYLNFVTEEMINPYRNLPLAIIISLPIVTLVYVLTNLAYFTTL
  STEQMLSSEAVAVDFGNYHLGVMSWIIPVFVGLSCFGSVNGSLFTSSRLFFVGSREGHLP
  SILSMIHPQLLTPVPSLVFTCVMTLLYAFSKDIFSVINFFSFFNWLCVALAIIGMIWLRH
  RKPELERPIKVNLALPVFFILACLFLIAVSFWKTPVECGIGFTIILSGLPVYFFGVWWKN
  KPKWLLQGIFSTTVLCQKLMQVVPQET
• Function: The heterodimer with SLC3A2 functions as a sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine, isoleucine and alanine. The heterodimer with SLC3A2 mediates the uptake of L-DOPA. Functions as an amino acid exchanger. May play a role in the transport of L-DOPA across the blood-brain barrier. May act as the major transporter of tyrosine in fibroblasts (Probable). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier.Can mediate the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane. When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation. Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane ; (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis.
• Tissue Specificity: Detected in placenta, in the syncytiotrophoblast layer (at protein level) . Expressed abundantly in adult lung, liver, brain, skeletal muscle, placenta, bone marrow, testis, resting lymphocytes and monocytes, and in fetal liver. Weaker expression in thymus, cornea, retina, peripheral leukocytes, spleen, kidney, colon and lymph node. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. Also expressed in all human tumor cell lines tested and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line Caco-2.
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway:
  Amino acid transport across the plasma membrane (R-HSA-352230)
  Tryptophan catabolism (R-HSA-71240)
  Basigin interactions (R-HSA-210991)
• BioCyc Pathway: MetaCyc:ENSG00000103257-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Large neutral amino acids transporter small subunit 1 (SLC7A5) affects the response to substance of Etoposide.	[52]
Mitoxantrone	DMM39BF	Approved	Large neutral amino acids transporter small subunit 1 (SLC7A5) affects the response to substance of Mitoxantrone.	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[10]

58 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 Large neutral amino acids transporter small subunit 1 (SLC7A5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[16]
Selenium	DM25CGV	Approved	Selenium increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[19]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[21]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[22]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[23]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[24]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[25]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[26]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[27]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[28]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[28]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[29]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[28]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[28]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[28]
Estrone	DM5T6US	Approved	Estrone increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[20]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[30]
Isoniazid	DM5JVS3	Approved	Isoniazid decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[31]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[20]
L-tryptophan	DMIBH7M	Approved	L-tryptophan increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[32]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[19]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[33]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[34]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[35]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[36]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[37]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[41]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[42]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[45]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[46]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[47]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[48]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[31]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[49]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[50]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[51]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Large neutral amino acids transporter small subunit 1 (SLC7A5).	[34]

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