Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T48330
(Former ID: TTDR00626)
|
|||||
| Target 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
Click to Show/Hide
|
|||||
| Gene Name |
SLC7A5
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| 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.
Click to Show/Hide
|
|||||
| BioChemical Class |
Amino acid-polyamine-organocation
|
|||||
| UniProt ID | ||||||
| Sequence |
MAGAGPKRRALAAPAAEEKEEAREKMLAAKSADGSAPAGEGEGVTLQRNITLLNGVAIIV
GTIIGSGIFVTPTGVLKEAGSPGLALVVWAACGVFSIVGALCYAELGTTISKSGGDYAYM LEVYGSLPAFLKLWIELLIIRPSSQYIVALVFATYLLKPLFPTCPVPEEAAKLVACLCVL LLTAVNCYSVKAATRVQDAFAAAKLLALALIILLGFVQIGKGDVSNLDPNFSFEGTKLDV GNIVLALYSGLFAYGGWNYLNFVTEEMINPYRNLPLAIIISLPIVTLVYVLTNLAYFTTL STEQMLSSEAVAVDFGNYHLGVMSWIIPVFVGLSCFGSVNGSLFTSSRLFFVGSREGHLP SILSMIHPQLLTPVPSLVFTCVMTLLYAFSKDIFSVINFFSFFNWLCVALAIIGMIWLRH RKPELERPIKVNLALPVFFILACLFLIAVSFWKTPVECGIGFTIILSGLPVYFFGVWWKN KPKWLLQGIFSTTVLCQKLMQVVPQET Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T28TAQ | |||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Cholesterol | Ligand Info | |||||
| Structure Description | LAT1-CD98hc complex bound to MEM-108 Fab | PDB:6JMQ | ||||
| Method | Electron microscopy | Resolution | 3.31 Å | Mutation | No | [3] |
| PDB Sequence |
ITLLNGVAII
59 VGTIIGSGIF69 VTPTGVLKEA79 GSPGLALVVW89 AACGVFSIVG99 ALCYAELGTT 109 ISKSGGDYAY119 MLEVYGSLPA129 FLKLWIELLI139 IRPSSQYIVA149 LVFATYLLKP 159 LFPTCPVPEE169 AAKLVACLCV179 LLLTAVNCYS189 VKAATRVQDA199 FAAAKLLALA 209 LIILLGFVQI219 FSFEGTKLDV240 GNIVLALYSG250 LFAYGGWNYL260 NFVTEEMINP 270 YRNLPLAIII280 SLPIVTLVYV290 LTNLAYFTTL300 STEQMLSSEA310 VAVDFGNYHL 320 GVMSWIIPVF330 VGLSCFGSVN340 GSLFTSSRLF350 FVLLTPVPSL377 VFTCVMTLLY 387 AFSKDIFSVI397 NFFSFFNWLC407 VALAIIGMIW417 LRHRKPELER427 PIKVNLALPV 437 FFILACLFLI447 AVSFWKTPVE457 CGIGFTIILS467 GLPVYFFGVW477 WKN |
|||||
|
|
LEU138
4.239
ILE139
4.025
PHE152
4.885
LEU156
3.717
PRO159
3.566
LEU160
4.969
GLU169
3.348
LYS172
3.874
LEU173
3.762
LEU180
4.356
THR183
4.193
ALA184
4.133
CYS187
3.721
TYR188
4.061
TRP325
4.643
PRO328
4.751
VAL329
3.702
LEU333
3.732
PHE336
3.655
VAL378
3.752
CYS381
4.177
VAL382
3.848
|
|||||
| Ligand Name: 3,5-diiodo-L-tyrosine | Ligand Info | |||||
| Structure Description | Overall structure of the LAT1-4F2hc bound with 3,5-diiodo-L-tyrosine | PDB:7DSQ | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [4] |
| PDB Sequence |
VTLQRNITLL
53 NGVAIIVGTI63 IGSGIFVTPT73 GVLKEAGSPG83 LALVVWAACG93 VFSIVGALCY 103 AELGTTISKS113 GGDYAYMLEV123 YGSLPAFLKL133 WIELLIIRPS143 SQYIVALVFA 153 TYLLKPLFPT163 CPVPEEAAKL173 VACLCVLLLT183 AVNCYSVKAA193 TRVQDAFAAA 203 KLLALALIIL213 LGFVQIGKGD223 VSNLDPNFSF233 EGTKLDVGNI243 VLALYSGLFA 253 YGGWNYLNFV263 TEEMINPYRN273 LPLAIIISLP283 IVTLVYVLTN293 LAYFTTLSTE 303 QMLSSEAVAV313 DFGNYHLGVM323 SWIIPVFVGL333 SCFGSVNGSL343 FTSSRLFFVG 353 SREGHLPSIL363 SMIHPQLLTP373 VPSLVFTCVM383 TLLYAFSKDI393 FSVINFFSFF 403 NWLCVALAII413 GMIWLRHRKP423 ELERPIKVNL433 ALPVFFILAC443 LFLIAVSFWK 453 TPVECGIGFT463 IILSGLPVYF473 FGVWWKNKPK483 WLLQGIFSTT493 VLCQKLMQVV 503 PQET
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| mTOR signaling pathway | hsa04150 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.50E-01 | Radiality | 1.20E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 8.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Central carbon metabolism in cancer | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| 2 | TGF_beta_Receptor Signaling Pathway | |||||
| Pathwhiz Pathway | [+] 2 Pathwhiz Pathways | + | ||||
| 1 | Kidney Function | |||||
| 2 | Leucine Stimulation on Insulin Signaling | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Basigin interactions | |||||
| 2 | Amino acid transport across the plasma membrane | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Nuclear Receptors Meta-Pathway | |||||
| 2 | Aryl Hydrocarbon Receptor Pathway | |||||
| 3 | Transport of inorganic cations/anions and amino acids/oligopeptides | |||||
| 4 | Cell surface interactions at the vascular wall | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Amino acid transporter molecule as a drug target. Nippon Yakurigaku Zasshi. 1999 Oct;114 Suppl 1:11P-16P. | |||||
| REF 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. | |||||
| REF 3 | Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc. Nat Struct Mol Biol. 2019 Jun;26(6):510-517. | |||||
| REF 4 | Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter. Cell Discov. 2021 Mar 23;7(1):16. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.