Target Information
| Target General Information | Top | |||||
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| Target ID |
T95842
(Former ID: TTDR00653)
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| Target Name |
Monocarboxylate transporter 1 (SLC16A1)
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| Synonyms |
Solute carrier family 16 member 1; MCT1; MCT 1
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| Gene Name |
SLC16A1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bodies. Required for normal nutrient assimilation, increase of white adipose tissue and body weight gain when on a high-fat diet. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate, small molecules that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis. Proton-coupled monocarboxylate transporter.
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| BioChemical Class |
Major facilitator
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| UniProt ID | ||||||
| Sequence |
MPPAVGGPVGYTPPDGGWGWAVVIGAFISIGFSYAFPKSITVFFKEIEGIFHATTSEVSW
ISSIMLAVMYGGGPISSILVNKYGSRIVMIVGGCLSGCGLIAASFCNTVQQLYVCIGVIG GLGLAFNLNPALTMIGKYFYKRRPLANGLAMAGSPVFLCTLAPLNQVFFGIFGWRGSFLI LGGLLLNCCVAGALMRPIGPKPTKAGKDKSKASLEKAGKSGVKKDLHDANTDLIGRHPKQ EKRSVFQTINQFLDLTLFTHRGFLLYLSGNVIMFFGLFAPLVFLSSYGKSQHYSSEKSAF LLSILAFVDMVARPSMGLVANTKPIRPRIQYFFAASVVANGVCHMLAPLSTTYVGFCVYA GFFGFAFGWLSSVLFETLMDLVGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYK YTYWACGVVLIISGIYLFIGMGINYRLLAKEQKANEQKKESKEEETSIDVAGKPNEVTKA AESPDQKDTDGGPKEEESPV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T02M5I | |||||
| 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-lactic acid | Ligand Info | |||||
| Structure Description | Cryo-EM structure of human MCT1 in complex with Basigin-2 in the presence of lactate | PDB:6LZ0 | ||||
| Method | Electron microscopy | Resolution | 3.30 Å | Mutation | No | [2] |
| PDB Sequence |
GGWGWAVVIG
25 AFISIGFSYA35 FPKSITVFFK45 EIEGIFHATT55 SEVSWISSIM65 LAVMYGGGPI 75 SSILVNKYGS85 RIVMIVGGCL95 SGCGLIAASF105 CNTVQQLYVC115 IGVIGGLGLA 125 FNLNPALTMI135 GKYFYKRRPL145 ANGLAMAGSP155 VFLCTLAPLN165 QVFFGIFGWR 175 GSFLILGGLL185 LNCCVAGALM195 RPIGPHRGFL264 LYLSGNVIMF274 FGLFAPLVFL 284 SSYGKSQHYS294 SEKSAFLLSI304 LAFVDMVARP314 SMGLVANTKP324 IRPRIQYFFA 334 ASVVANGVCH344 MLAPLSTTYV354 GFCVYAGFFG364 FAFGWLSSVL374 FETLMDLVGP 384 QRFSSAVGLV394 TIVECCPVLL404 GPPLLGRLND414 MYGDYKYTYW424 ACGVVLIISG 434 IYLFIGMGIN444 YRLLA
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| Ligand Name: 7-(Benzyl(methyl)amino)-2-oxo-2H-chromene-3-carboxylic acid | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the human MCT1/Basigin-2 complex in the presence of anti-cancer drug candidate 7ACC2 in the inward-open conformation | PDB:7CKO | ||||
| Method | Electron microscopy | Resolution | 2.95 Å | Mutation | No | [2] |
| PDB Sequence |
GGWGWAVVIG
25 AFISIGFSYA35 FPKSITVFFK45 EIEGIFHATT55 SEVSWISSIM65 LAVMYGGGPI 75 SSILVNKYGS85 RIVMIVGGCL95 SGCGLIAASF105 CNTVQQLYVC115 IGVIGGLGLA 125 FNLNPALTMI135 GKYFYKRRPL145 ANGLAMAGSP155 VFLCTLAPLN165 QVFFGIFGWR 175 GSFLILGGLL185 LNCCVAGALM195 RPIGPHRGFL264 LYLSGNVIMF274 FGLFAPLVFL 284 SSYGKSQHYS294 SEKSAFLLSI304 LAFVDMVARP314 SMGLVANTKP324 IRPRIQYFFA 334 ASVVANGVCH344 MLAPLSTTYV354 GFCVYAGFFG364 FAFGWLSSVL374 FETLMDLVGP 384 QRFSSAVGLV394 TIVECCPVLL404 GPPLLGRLND414 MYGDYKYTYW424 ACGVVLIISG 434 IYLFIGMGIN444 YRLLA
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| 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).
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
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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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.79E-01 | Radiality | 1.29E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.20E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues. Neuroreport. 2001 Mar 26;12(4):761-5. | |||||
| REF 2 | Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates. Cell. 2021 Jan 21;184(2):370-383.e13. | |||||
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