Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPH2JB)

• DTT Name: Large neutral amino acids transporter 1 (SLC7A5)
• Synonyms: y+ system cationic amino acid transporter; Solute carrier family 7 member 5; MPE16; Large neutral amino acids transporter small subunit 1; LAT1; L-type amino acid transporter LAT1; L-type amino acid transporter 1; Integral membrane protein E16; HLAT1; CD98LC; CD98 light chain; 4F2LC; 4F2 light chain; 4F2 LC
• Gene Name: SLC7A5
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Amino acid-polyamine-organocation
• UniProt ID: LAT1_HUMAN
• TTD ID: T48330
• Sequence:
  MAGAGPKRRALAAPAAEEKEEAREKMLAAKSADGSAPAGEGEGVTLQRNITLLNGVAIIV
  GTIIGSGIFVTPTGVLKEAGSPGLALVVWAACGVFSIVGALCYAELGTTISKSGGDYAYM
  LEVYGSLPAFLKLWIELLIIRPSSQYIVALVFATYLLKPLFPTCPVPEEAAKLVACLCVL
  LLTAVNCYSVKAATRVQDAFAAAKLLALALIILLGFVQIGKGDVSNLDPNFSFEGTKLDV
  GNIVLALYSGLFAYGGWNYLNFVTEEMINPYRNLPLAIIISLPIVTLVYVLTNLAYFTTL
  STEQMLSSEAVAVDFGNYHLGVMSWIIPVFVGLSCFGSVNGSLFTSSRLFFVGSREGHLP
  SILSMIHPQLLTPVPSLVFTCVMTLLYAFSKDIFSVINFFSFFNWLCVALAIIGMIWLRH
  RKPELERPIKVNLALPVFFILACLFLIAVSFWKTPVECGIGFTIILSGLPVYFFGVWWKN
  KPKWLLQGIFSTTVLCQKLMQVVPQET
• Function: Involved in cellular amino acid uptake. Acts as an amino acid exchanger. Involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Plays a role in neuronal cell proliferation (neurogenesis) in brain. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. May play an important role in high-grade gliomas. Mediates blood-to-retina L-leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts. When associated with LAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation. Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc.
• KEGG Pathway: Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway:
  Amino acid transport across the plasma membrane (R-HSA-352230)
  Basigin interactions (R-HSA-210991)
• BioCyc Pathway: MetaCyc:ENSG00000103257-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)-2-Amino-1,2,3,4-tetrahydro-2-naphthoic acid	DMX768L	Discovery agent	N.A.	Investigative	[2]
(+/-)-2-Aminoindane-2-carboxylic acid	DML5URN	Discovery agent	N.A.	Investigative	[2]
BCH	DM9IN0U	Discovery agent	N.A.	Investigative	[1]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: L-type amino acid transporter 1 (SLC7A5) DTP Info
• Gene Name: SLC7A5

4 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[3]
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[4]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[5]
Pregabalin	DMDVP3B	Chronic obstructive pulmonary disease	CA22	Approved	[6]

1 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-leucine	DMQHN7I	Discovery agent	N.A.	Investigative	[4]

References

• [1] Amino acid transporter molecule as a drug target. Nippon Yakurigaku Zasshi. 1999 Oct;114 Suppl 1:11P-16P.
• [2] Regiospecific and conformationally restrained analogs of melphalan and DL-2-NAM-7 and their affinities for the large neutral amino acid transporter... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3688-91.
• [3] Transport of gabapentin by LAT1 (SLC7A5). Biochem Pharmacol. 2013 Jun 1;85(11):1672-83.
• [4] Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009 Feb 6;136(3):521-34.
• [5] Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol. Sci Rep. 2017 Mar 8;7:43580.
• [6] Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharm Res. 2018 Oct 29;35(12):246.