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solute carrier family 3A2; 4F2 cell-surface antigen heavy chain; 4F2hc; lymphocyte activation antigen 4F2 large subunit; 4F2 heavy chain antigen; CD98 (SLC3A2, MDU1)

Function: - amino acid transporter, involved in function of: a) pancreatic islet cells b) thyroid C cells c) parathyroid cells - 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 Kinetic parameters: - 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.

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein membrane protein phosphoprotein solute carrier family 3 (SLC3, SLC3A)

Properties

SIZE: entity length = 529 aa MW = 58 kD COMPARTMENT: plasma membrane MOTIF: Ser phosphorylation site {S2} Thr phosphorylation site {T5} transmembrane domain {82-104} cysteine residue {C109} MODIFICATION: cysteine residue {C-INTERCHAIN} N-glycosylation site {N264} N-glycosylation site {N280} N-glycosylation site {N323} N-glycosylation site {N405}

Database Correlations

OMIM 158070 UniProt P08195 Pfam PF00128 Entrez Gene 6520 Kegg hsa:6520

References

  1. Uniprot :accession P08195
  2. http://www.pathologyoutlines.com/cdmarkers.html 11 June 2005
  3. Protein Reviews on the Web http://mpr.nci.nih.gov/prow/guide/1678237818_g.htm
  4. 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: 11840567