Target Information
| Target General Information | Top | |||||
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| Target ID |
T59493
(Former ID: TTDI03023)
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| Target Name |
Alanine/serine/cysteine transporter 2 (SLC1A5)
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| Synonyms |
Solute carrier family 1 member 5; Sodium-dependent neutral amino acid transporter type 2; RDRC; RDR; RD114/simian type D retrovirus receptor; Neutral amino acid transporter B(0); M7V1; Baboon M7 virus receptor; ATB(0); ASCT2
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| Gene Name |
SLC1A5
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids. Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development.
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| UniProt ID | ||||||
| Sequence |
MVADPPRDSKGLAAAEPTANGGLALASIEDQGAAAGGYCGSRDQVRRCLRANLLVLLTVV
AVVAGVALGLGVSGAGGALALGPERLSAFVFPGELLLRLLRMIILPLVVCSLIGGAASLD PGALGRLGAWALLFFLVTTLLASALGVGLALALQPGAASAAINASVGAAGSAENAPSKEV LDSFLDLARNIFPSNLVSAAFRSYSTTYEERNITGTRVKVPVGQEVEGMNILGLVVFAIV FGVALRKLGPEGELLIRFFNSFNEATMVLVSWIMWYAPVGIMFLVAGKIVEMEDVGLLFA RLGKYILCCLLGHAIHGLLVLPLIYFLFTRKNPYRFLWGIVTPLATAFGTSSSSATLPLM MKCVEENNGVAKHISRFILPIGATVNMDGAALFQCVAAVFIAQLSQQSLDFVKIITILVT ATASSVGAAGIPAGGVLTLAIILEAVNLPVDHISLILAVDWLVDRSCTVLNVEGDALGAG LLQNYVDRTESRSTEPELIQVKSELPLDPLPVPTEEGNPLLKHYRGPAGDATVASEKESV M Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T53ZJN | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: L-glutamine | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the human neutral amino acid transporter ASCT2 | PDB:6MPB | ||||
| Method | Electron microscopy | Resolution | 3.84 Å | Mutation | No | [3] |
| PDB Sequence |
DQVRRCLRAN
52 LLVLLTVVAV62 VAGVALGLGV72 SGAGGALALG82 PERLSAFVFP92 GELLLRLLRM 102 IILPLVVCSL112 IGGAASLDPG122 ALGRLGAWAL132 LFFLVTTLLA142 SALGVGLALA 152 LQPGAASAAI162 NASVGAAGSA172 ENAPSKEVLD182 SFLDLARNIF192 PSNLVSAAFR 202 SYSTTYEERN212 ITGTRVKVPV222 GQEVEGMNIL232 GLVVFAIVFG242 VALRKLGPEG 252 ELLIRFFNSF262 NEATMVLVSW272 IMWYAPVGIM282 FLVAGKIVEM292 EDVGLLFARL 302 GKYILCCLLG312 HAIHGLLVLP322 LIYFLFTRKN332 PYRFLWGIVT342 PLATAFGTSS 352 SSATLPLMMK362 CVEENNGVAK372 HISRFILPIG382 ATVNMDGAAL392 FQCVAAVFIA 402 QLSQQSLDFV412 KIITILVTAT422 ASSVGAAGIP432 AGGVLTLAII442 LEAVNLPVDH 452 ISLILAVDWL462 VDRSCTVLNV472 EGDALGAGLL482 QNYVDR
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SER351
3.916
SER352
3.351
SER353
2.487
SER354
4.293
MET387
4.695
ALA390
3.338
PHE393
4.974
ALA428
4.894
ALA429
3.390
GLY430
3.538
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: L-aspartic acid | Ligand Info | |||||
| Structure Description | Structure of the thermostalilized EAAT1 cryst-II mutant in complex with L-ASP and the allosteric inhibitor UCPH101 | PDB:5LM4 | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [4] |
| PDB Sequence |
EDVKSFLRRN
48 ALLLLTVLAV58 ILGVVLGFLL68 RPYPLSPREV78 KYFAFPGELL88 MRMLKMLILP 98 LIVSSLITGL108 ASLDAKASGR118 LGMRAVVYYM128 STTIIAVVLG138 IILVLIIEVL 173 DCFLDLARNI183 FPSNLVSAAF193 RSYSTQEVEG220 MNILGLVVFS230 IVFGIALGKM 240 GEQGQLLVDF250 FNSLNEATMK260 LVAIIMWYAP270 LGILFLIAGK280 IVEGMYMVTV 301 IVGLVIHGLI311 VLPLIYFLIT321 RKNPFVFIAG331 ILQALITALG341 TSSSSATLPI 351 TFKCLEENNG361 VDKRITRFVL371 PVGATINMDG381 TALYEAVAAI391 FIAQDFGQII 407 TISITATAAS417 IGAAGIPQAG427 LVTMVIVLTA437 VGLPTDDITL447 IIAVDWLLDR 457 FRTMVNVLGD467 ALGAGIVEHL477 SRKELEKQD
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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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.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Protein digestion and absorption | hsa04974 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.66E-01 | Radiality | 1.25E+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 |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Ngamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site. Bioorg Med Chem. 2005 Feb 15;13(4):1111-8. | |||||
| REF 2 | New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J Physiol. 2004 Jun 15;557(Pt 3):747-59. | |||||
| REF 3 | Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation. Elife. 2019 Oct 3;8:e48120. | |||||
| REF 4 | Structure and allosteric inhibition of excitatory amino acid transporter 1. Nature. 2017 Apr 27;544(7651):446-451. | |||||
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