ID:4F2_HUMAN DESCRIPTION: RecName: Full=4F2 cell-surface antigen heavy chain; Short=4F2hc; AltName: Full=4F2 heavy chain antigen; AltName: Full=Lymphocyte activation antigen 4F2 large subunit; AltName: CD_antigen=CD98; FUNCTION: 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. 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. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, 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. 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. BIOPHYSICOCHEMICAL PROPERTIES: 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); SUBUNIT: Disulfide-linked heterodimer of a glycosylated heavy chain and a non-glycosylated light chain (SLC7A5, SLC7A6, SLCA7A7, SLC7A8, SLC7A10 or SLCA7A11). Colocalizes with cadherins (By similarity). Interacts with FAM57A/CT120 and ICAM1. 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 (By similarity). 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 (By similarity). TISSUE SPECIFICITY: 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. Expressed in HUVECS and at low levels in resting peripheral blood T-lymphocytes and quiescent fibroblasts. Also expressed in fetal liver and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line Caco-2 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. PTM: 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. MASS SPECTROMETRY: Mass=57944.93; Method=MALDI; Range=1-529; Source=PubMed:11840567; MISCELLANEOUS: Arginine uptake is inhibited by increasing concentrations of leucine in the presence of Na(+). SIMILARITY: Belongs to the SLC3A transporter family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P08195
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC001061 - Homo sapiens solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2, mRNA (cDNA clone MGC:2307 IMAGE:3505759), complete cds. AK025584 - Homo sapiens cDNA: FLJ21931 fis, clone HEP04314, highly similar to AB018010 Homo sapiens mRNA for 4F2 heavy chain. BC003000 - Homo sapiens solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2, mRNA (cDNA clone MGC:3977 IMAGE:2821990), complete cds. J03569 - Human lymphocyte activation antigen 4F2 large subunit mRNA, complete cds. AK090758 - Homo sapiens cDNA FLJ33439 fis, clone BRACE2021695, highly similar to 4F2 CELL-SURFACE ANTIGEN HEAVY CHAIN. AX746603 - Sequence 128 from Patent EP1308459. AK304497 - Homo sapiens cDNA FLJ54090 complete cds, highly similar to 4F2 cell-surface antigen heavy chain. AB018010 - Homo sapiens mRNA for 4F2 heavy chain, complete cds. J02939 - Human membrane glycoprotein 4F2 antigen heavy chain mRNA. AK225304 - Homo sapiens mRNA for solute carrier family 3, member 2 isoform a variant, clone: HEP01460. J02769 - Human 4F2 antigen heavy chain mRNA, complete cds. EU832683 - Synthetic construct Homo sapiens clone HAIB:100067712; DKFZo004A0732 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2 protein (SLC3A2) gene, encodes complete protein. EU832612 - Synthetic construct Homo sapiens clone HAIB:100067641; DKFZo008A0731 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2 protein (SLC3A2) gene, encodes complete protein. KJ892151 - Synthetic construct Homo sapiens clone ccsbBroadEn_01545 SLC3A2 gene, encodes complete protein. E41391 - Amino acid transporting protein and gene thereof. HV815688 - JP 2011083284-A/23: Amino Acid Transporter And Gene Thereof. HV815711 - JP 2011084564-A/23: Amino Acid Transporter And Gene Thereof. AK308797 - Homo sapiens cDNA, FLJ98838. AK311592 - Homo sapiens cDNA, FLJ18634. AF055031 - Homo sapiens clone 24551 mRNA sequence. AK094620 - Homo sapiens cDNA FLJ37301 fis, clone BRAMY2015911, highly similar to 4F2 CELL-SURFACE ANTIGEN HEAVY CHAIN. AK304685 - Homo sapiens cDNA FLJ53699 complete cds, moderately similar to 4F2 cell-surface antigen heavy chain. JD025276 - Sequence 6300 from Patent EP1572962. JD034729 - Sequence 15753 from Patent EP1572962. JD539799 - Sequence 520823 from Patent EP1572962. JD058877 - Sequence 39901 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P08195 (Reactome details) participates in the following event(s):
R-HSA-375131 Basigin binds CD98 complex R-HSA-352191 Metabolism of nitrogenous molecules R-HSA-352232 Metabolism of nitrogenous molecules R-HSA-376200 Metabolism of nitrogenous molecules R-HSA-378513 SLC7A11-mediated exchange of extracellular cysteine and cytosolic glutamate R-HSA-379426 SLC7A6 (y+LAT2)-mediated exchange of extracellular leucine for cytosolic arginine R-HSA-379415 SLC7A7:SLC3A2 exchanges L-Arg for L-Leu, Na+ across the plasma membrane R-HSA-210991 Basigin interactions R-HSA-352230 Amino acid transport across the plasma membrane R-HSA-71240 Tryptophan catabolism R-HSA-202733 Cell surface interactions at the vascular wall R-HSA-425374 Amino acid and oligopeptide SLC transporters R-HSA-425393 Metabolism of nitrogenous molecules R-HSA-6788656 Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism R-HSA-109582 Hemostasis R-HSA-425407 SLC-mediated transmembrane transport R-HSA-71291 Metabolism of nitrogenous molecules R-HSA-382551 Transport of small molecules R-HSA-1430728 Metabolism
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
