CD98 (SLC3A2)

CD98 is required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. CD98 is involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. CD98 plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. CD98 is required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, CD98 is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. CD98 is 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. When associated with SLC7A5 or SLC7A8, 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 LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier.

CD98 (SLC3A2) Related Areas

Immunology>>Cluster of Differentiation>>CD98/SLC3A2

Cancer>>Cancer Biomarkers>>CD98/SLC3A2

CD98 (SLC3A2) Alternative Names

CD98, SLC3A2, 4F2, 4F2HC, 4T2HC, CD98HC, MDU1, NACAE [Homo sapiens]

Cd98, Slc3a2, 4F2, 4F2HC, AI314110, Ly-10, Ly-m10, Ly10, Mdu1, Mgp-2hc, NACAE [Mus musculus]

Summaries for CD98 (SLC3A2)

Entrez Gene summary for SLC3A2:

This SLC3A2 gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. CD98 exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. CD98 plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

Wikipedia summary for CD98:

CD98 is a glycoprotein that is a heterodimer composed of SLC3A2 and SLC7A5 that forms the large neutral amino acid transporter (LAT1). LAT1 is a heterodimeric membrane transport protein that preferentially transports branched-chain (valine, leucine, isoleucine) and aromatic (tryptophan, tyrosine) amino acids. LAT is highly expressed in brain capillaries (which form the blood-brain barrier) relative to other tissues.

Human CD98 (SLC3A2) Protein General Information

 

• Protein names: CD_antigen=CD98
• Sequence length: 630 AA.
• Sequence similarities: CD98 belongs to the SLC3A transporter family.
• Post-translational modification: Phosphorylation on Ser-406; Ser-408 or Ser-410 and on Ser-527 or Ser-531 by ecto-protein kinases favors heterotypic cell-cell interactions.
• Subunit structure: Disulfide-linked heterodimer of a glycosylated heavy chain and a non-glycosylated light chain (SLC7A5, SLC7A6, SLCA7A7, SLC7A8, SLC7A10 or SLCA7A11). Colocalizes with cadherins. CD98 interacts with FAM57A/CT120 and ICAM1. CD98 constitutively and specifically associates with beta-1 integrins (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1), but minimally with alpha-4/beta-1.
• Subcellular location: Apical cell membrane; Single-pass type II membrane protein. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Localized to the plasma membrane when associated with SLC7A5 or SLC7A8. Localized to the placental apical membrane. Located selectively at cell-cell adhesion sites. Colocalized with SLC7A8/LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. Expressed in both luminal and abluminal membranes of brain capillary endothelial cells
• Tissue specificity: CD98 is expressed ubiquitously in all tissues tested with highest levels detected in kidney, placenta and testis and weakest level in thymus. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. CD98 is expressed in HUVECS and at low levels in resting peripheral blood T-lymphocytes and quiescent fibroblasts. CD98 is also expressed in fetal liver and in the astrocytic process of primary astrocytic gliomas. CD98 is expressed in retinal endothelial cells and in the intestinal epithelial cell line Caco2-BBE.
• Induction: Expression is induced in resting peripheral blood T-lymphocytes following PHA stimulation. Expression increases at the time of maximal DNA synthesis, in fibroblasts stimulated to divide. Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore.
• Miscellaneous: Arginine uptake is inhibited by increasing concentrations of leucine in the presence of Na+.
• Biophysicochemical properties: Kinetic parameters:
  KM=295 µM for glutamine (in the presence of NaCl)
  KM=236 µM for leucine (in the presence of NaCl)
  KM=120 µM for arginine (in the presence of NaCl)
  KM=138 µM for arginine (in the absence of NaCl)
• Mass spectrometry: Molecular mass is 57944.93 Da from positions 1 - 529. Determined by MALDI.

General information above from UniProt

Function for CD98 (SLC3A2) Protein

UniProtKB:

CD98 is required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. CD98 is involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. CD98 plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. CD98 is required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, CD98 is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. CD98 is 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. When associated with SLC7A5 or SLC7A8, 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 LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier.

Genatlas:

• CD98 is involved in T cell activation and in normal and neoplastic cell growth
• CD98 can control the capacity of cells to assemble an Fibronectin matrix, a process important in development, wound healing, and tumorigenesis (Feral 2007)
• CD98 may cooperate with other cytoplasmic domain binding proteins to modulate integrin functions and into the evolution of integrin signaling
• CD98 is involved in the export of the diamine putrescine and monoacetylated spermidine
• extracellular signaling through ecto-protein kinases (EPKs) might lead to ecto-phosphorylation of CD98 and influence its multiple functions, including its role in cell-cell interactions (Nguyen 2008)
• CD98 mediates notoriously invasive activity of extravillous trophoblast by promoting alpha(v)beta(3) integrin-dependent signals (Kabir-Salmani 2008)