Molecule Information

General Information of the Molecule (ID: Mol04043)

• Name: L-type amino acid transporter 2 (LAT2) ,Homo sapiens
• Synonyms: L-type amino acid transporter 2; Solute carrier family 7 member 8
• Molecule Type: Protein
• Gene Name: SLC7A8
• Gene ID: 23428
• Location: chr14:23125295-23183674[-]
• Sequence:
  MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGNIIGSGIFV
  SPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVKDIFGGLAGF
  LRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICLLLLTWVNCSSV
  RWATRVQDIFTAGKLLALALIIIMGIVQICKGEYFWLEPKNAFENFQEPDIGLVALAFLQ
  GSFAYGGWNFLNYVTEELVDPYKNLPRAIFISIPLVTFVYVFANVAYVTAMSPQELLASN
  AVAVTFGEKLLGVMAWIMPISVALSTFGGVNGSLFTSSRLFFAGAREGHLPSVLAMIHVK
  RCTPIPALLFTCISTLLMLVTSDMYTLINYVGFINYLFYGVTVAGQIVLRWKKPDIPRPI
  KINLLFPIIYLLFWAFLLVFSLWSEPVVCGIGLAIMLTGVPVYFLGVYWQHKPKCFSDFI
  ELLTLVSQKMCVVVYPEVERGSGTEEANEDMEEQQQPMYQPTPTKDKDVAGQPQP
• 3D-structure: PDB ID: 8A6L; Classification: Membrane protein; Method: Electron microscopy; Resolution: 3.18 Å
• Function: Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1. Functions as amino acid antiporter mediating the influx of extracellular essential amino acids mainly in exchange with the efflux of highly concentrated intracellular amino acids (PubMed:10391915, PubMed:11311135, PubMed:11847106, PubMed:12716892, PubMed:15081149, PubMed:15918515, PubMed:29355479, PubMed:33298890, PubMed:34848541). Has relatively symmetrical selectivities but strongly asymmetrical substrate affinities at both the intracellular and extracellular sides of the transporter (PubMed:11847106). This asymmetry allows SLC7A8 to regulate intracellular amino acid pools (mM concentrations) by exchange with external amino acids (uM concentration range), equilibrating the relative concentrations of different amino acids across the plasma membrane instead of mediating their net uptake (PubMed:10391915, PubMed:11847106). May play an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney (PubMed:12716892). 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 (PubMed:12117417). Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L- nitrosocysteine (L-CNSO) across the transmembrane (PubMed:15769744). Imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4) (By similarity). Mediates the uptake of L-DOPA (By similarity). May participate in auditory function (By similarity). .
• Uniprot ID: LAT2_HUMAN
• Ensembl ID: ENSG00000092068
• HGNC ID: HGNC:11066

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Cholangiocarcinoma [ICD-11: 2C12.00] [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.00]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KKU-213B cells; Liver; Homo sapiens (Human); CVCL_M264
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Moreover, in vivo experiments showed that a combination curcumin and gemcitabine significantly reduced tumor size, tumor growth rate and LAT2 expression in a gemcitabine-resistant CCA xenograft mouse model. Suppression of tumor progression in an orthotopic CCA hamster model provided strong support for clinical application. In conclusion, curcumin synergistically enhances gemcitabine efficacy against gemcitabine-resistant CCA by induction of apoptosis, partly via inhibiting LAT2/glutamine pathway.

Curcumin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Cholangiocarcinoma [ICD-11: 2C12.00] [1]

• Metabolic Type: Glutamine metabolism
• Sensitive Disease: Cholangiocarcinoma [ICD-11: 2C12.00]
• Sensitive Drug: Curcumin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KKU-213B cells; Liver; Homo sapiens (Human); CVCL_M264
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Moreover, in vivo experiments showed that a combination curcumin and gemcitabine significantly reduced tumor size, tumor growth rate and LAT2 expression in a gemcitabine-resistant CCA xenograft mouse model. Suppression of tumor progression in an orthotopic CCA hamster model provided strong support for clinical application. In conclusion, curcumin synergistically enhances gemcitabine efficacy against gemcitabine-resistant CCA by induction of apoptosis, partly via inhibiting LAT2/glutamine pathway.

References

• Ref 1: Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway. Sci Rep. 2024 Jul 11;14(1):16059.