solute carrier family 3A2; 4F2 cell-surface antigen heavy chain; 4F2hc; lymphocyte activation antigen 4F2 large subunit; 4F2 heavy chain antigen; CD98 (SLC3A2, MDU1)
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Function
- amino acid transporter, involved in function of:
- required for light chain amino-acid transporters
- role in Na+-independent, high-affinity transport of large neutral amino acids including: phenylalanine, tyrosine, leucine, arginine & tryptophan
- role in guiding & targeting of LAT1 & 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
- plays a role in nitric oxide synthesis in human umbilical vein endothelial cells via transport of L-arginine
- arginine uptake is inhibited by increasing concentrations of leucine in the presence of Na+
- required for normal & neoplastic cell growth
- when associated with SLC7A5/LAT1, is also involved in the transport of L-DOPA across the blood-brain barrier, & that of thyroid hormones triiodothyronine (T3) & thyroxine (T4) across the cell membrane in tissues such as placenta
- role in uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, & hence plays a role in metal ion homeostasis & 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 transport of LAT2 in polarized intestinal cells, by generating & delivering intracellular signals
- when associated with SLC7A5, plays a role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier
- disulfide-linked heterodimer of a glycosylated heavy chain & a non-glycosylated light chain (SLC7A5, SLC7A6, SLCA7A7, SLC7A8, SLC7A10 or SLCA7A11)
- colocalizes with cadherins
- interacts with FAM57A/CT120 & ICAM1
- constitutively & specifically associates with beta-1 integrins (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 & alpha-6/beta-1), but minimally with alpha-4/beta-1
- KM=295 uM for glutamine (in the presence of NaCl)
- KM=236 uM for leucine (in the presence of NaCl)
- KM=120 uM for arginine (in the presence of NaCl)
- KM=138 uM for arginine (in the absence of NaCl)
Structure
- mass=57944.93 daltons[4]
- belongs to the SLC3A transporter family
Compartment
- apical cell membrane
- melanosome: stage 1-4
- localized to the plasma membrane when associated with SLC7A5 or SLC7A8
- localized to the placental apical membrane
- located selectively at cell-cell adhesion sites (putative)
- colocalized with SLC7A8/LAT2 at the basolateral membrane of kidney proximal tubules & small intestine epithelia
- expressed in both luminal & abluminal membranes of brain capillary endothelial cells (putative)
Expression
- expressed ubiquitously in all tissues tested with highest levels detected in kidney, placenta & testis
- weakest expression in thymus
- during gestation, expression in placenta is significantly stronger at full-term than at the mid-trimester stage
- expressed in human umbilical vein endothelial cells & at low levels in resting peripheral blood T-lymphocytes & quiescent fibroblasts
- also expressed in fetal liver & in the astrocytic process of primary astrocytic gliomas
- expressed in retinal endothelial cells & in the intestinal epithelial cell line Caco2-BBE
- expression is induced in resting peripheral blood T-cells following PHA stimulation
- expression increases at the time of maximal DNA synthesis, in fibroblasts stimulated to divide
- expression & the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA & Ca+2 ionophore
- upregulated on leukocytes in inflammatory lesions
- strongly expressed by neoplastic cells.
More general terms
References
- ↑ Uniprot http://www.uniprot.org/uniprot/P08195.html
- ↑ http://www.pathologyoutlines.com/cdmarkers.html 11 June 2005
- ↑ Protein Reviews on the Web http://mpr.nci.nih.gov/prow/guide/1678237818_g.htm
- ↑ 4.0 4.1 Harris RA et al Cluster analysis of an extensive human breast cancer cell line protein expression map database. Proteomics. 2002 Feb;2(2):212-23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11840567