Molecule Information

General Information of the Molecule (ID: Mol00002)

• Name: Lymphocyte activation antigen 4F2 (SLC3A2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: SLC3A2
• Gene ID: 6520
• Location: chr11:62856004-62888880[+]
• Sequence:
  MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPS
  ASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTMSQDTEVDMKEVELNELEP
  EKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVR
  TRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGN
  LAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKK
  SIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFL
  AEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVT
  QYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALP
  GQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGD
  FHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQ
  PGREEGSPLELERLKLEPHEGLLLRFPYAA
• Function: Component of several heterodimeric complexes involved in amino acid transport. The precise substrate specificity depends on the other subunit in the heterodimer. The complexes function as amino acid exchangers. The homodimer functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, L-DOPA, leucine, histidine, methionine and tryptophan. The heterodimer formed by SLC3A2 and SLC7A6 or SLC3A2 and SLC7A7 mediates the uptake of dibasic amino acids. The heterodimer with SLC7A5/LAT1 mediates the transport of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane. The heterodimer with SLC7A5/LAT1 is involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes. The heterodimer with SLC7A5/LAT1 is involved in the uptake of leucine. When associated with LAPTM4B, the heterodimer with SLC7A5/LAT1 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation. The heterodimer with SLC7A5/LAT1 may play a role in the transport of L-DOPA across the blood-brain barrier. The heterodimer formed by SLC3A2 and SLC7A5/LAT1 or SLC3A2 and SLC7A8/LAT2 is involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Together with ICAM1, regulates the transport activity of SLC7A8/LAT2 in polarized intestinal cells by generating and delivering intracellular signals. Required for targeting of SLC7A5/LAT1 and SLC7A8/LAT2 to the plasma membrane and for channel activity. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier.
• Uniprot ID: 4F2_HUMAN
• Ensembl ID: ENSG00000168003
• HGNC ID: HGNC:11026

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

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Hepatocellular carcinoma [1]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HCCLM3 cells; Liver; Homo sapiens (Human); CVCL_6832
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Overexpressed SNHG1 contributes to sorafenib resistance by activating the Akt pathway via regulating SLC3A2.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.35E-01; Fold-change: -9.84E-03; Z-score: -2.39E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.67E-03; Fold-change: 5.15E-02; Z-score: 1.23E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 5.25E-01; Fold-change: -1.83E-01; Z-score: -4.96E-01

References

• Ref 1: LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2019 May 3;38(1):183. doi: 10.1186/s13046-019-1177-0.