SLC3A2 Membrane Protein Introduction

Introduction of SLC3A2

4F2 cell-surface antigen heavy chain (4F2HC, also known as CD98, SLC3A2), is a subunit of multiple heterodimeric amino acid transporters that in human is encoded by the SLC3A2 gene. SLC3A2 is identified as a cell surface, type II transmembrane protein with an alpha-amylase domain and belongs to the solute carrier family 3 (SLC3). SLC3A2 is expressed ubiquitously in all tissues, determined at the highest levels detected in kidney, testis and placenta and weakest level in thymus. It is also found in retinal endothelial cells and in the intestinal epithelial cell line C2BBe1.

Basic Information of SLC3A2
Protein Name	4F2 cell-surface antigen heavy chain
Gene Name	SLC3A2
Aliases	4F2 heavy chain antigen, Lymphocyte activation antigen 4F2 large subunit, Solute carrier family 3 member 2, CD antigen: CD98
Organism	Homo sapiens (Human)
UniProt ID	P08195
Transmembrane Times	1
Length (aa)	661
Sequence	MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPSASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTETGFHHVSQADIEFLTSIDPTASASGSAGITGTMSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGNLAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKKSIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFLAEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVTQYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALPGQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGDFHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQPGREEGSPLELERLKLEPHEGLLLRFPYAA

Function of SLC3A2 Membrane Protein

SLC3A2 has been shown to interact with Y+L amino acid transporter 1 (encoded by SLC7A7), and hence functions as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, contributing to arginine release in exchange for extracellular amino acids. Moreover, it is a constituent member of the system xc- cystine/glutamate antiporter, complexing with cystine/glutamate transporter, an antiporter that in human is encoded by SLC7A11 gene. SLC3A2 is required for the function of light chain amino-acid transporters and is involved in the sodium-independent, high-affinity transport of large neutral amino acids including phenylalanine, leucine, tyrosine, tryptophan, and arginine. It is proved to contribute to guiding and targeting of LAT1 and LAT2 to the plasma membrane. SLC3A2 has been shown to play a role in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D, L-homocysteine complexes, and thus be involved in metal ion homeostasis and toxicity. Moreover, SLC3A2 is associated with integrins and mediates integrin-dependent signaling related to normal cell growth and tumorigenesis.

SLC3A2 Membrane Protein Introduction Fig.1 Structure of the SLC3A2.

Application of SLC3A2 Membrane Protein in Literature

Weng L., et al. Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex. Mol Med Rep. 2018, 16(3): e2005090. PubMed ID: 29538402

Authors of this study show the interaction between 4F2 heavy chain (4F2hc), a subunit of multiple amino acid transporters, and the multifunctional hub protein girders of actin filaments (Girdin) down-regulates mTORC1 activity.
Balthasar C., et al. Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter. Int J Mol Sci. 2017, 18(8). PubMed ID: 28786956

The results of this article suppose that MeHg is transported through LAT2-4F2hc, a system L amino acid transporter, and the system L is responsible for the uptake of amino acids and MeHg primarily at the apical membrane of the trophoblast.
Ohgaki R., et al. Essential Roles of L-Type Amino Acid Transporter 1 in Syncytiotrophoblast Development by Presenting Fusogenic 4F2hc. Mol Cell Biol. 2017, 37(11). PubMed ID: 28320871

This study reports a novel fundamental role of LAT1 to support the protein expression of 4F2hc through a chaperone-like function in chorionic trophoblasts.
Satoh T., et al. Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer. Anticancer Res. 2017, 37(2): 631-636. PubMed ID: 28179310

The results of this study indicate that CD98 (4F2hc) may be a novel predictive biomarker for worse prognosis in GC-affected patients.
Rosell A., et al. Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc. Proc Natl Acad Sci U S A. 2014, 111(8): 2966-2971. PubMed ID: 24516142

Results of this study suggest that the interaction of 4F2hc with LAT2 gives insights into the structural bases for light subunit recognition and the stabilizing role of the ancillary protein in HATs.

SLC3A2 Preparation Options

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