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4F2 cell-surface antigen heavy chain is a protein that in humans is encoded by the SLC3A2 (solute carrier family 3 member 2) gene.[1][2]

SLC3A2 comprises the heavy subunit of the large neutral amino acid transporter (LAT1) that is also known as CD98 (cluster of differentiation 98).[3][4]


SLC3A2 is a member of the solute carrier family and encodes a cell surface, transmembrane protein with an alpha-amylase domain. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. It associates with integrins and mediates integrin-dependent signaling related to normal cell growth and tumorigenesis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2]

LAT1 is a heterodimeric membrane transport protein that preferentially transports neutral branched (valine, leucine, isoleucine) and aromatic (tryptophan, tyrosine) amino acids.[5] LAT is highly expressed in brain capillaries (which form the blood brain barrier) relative to other tissues.[5]

A functional LAT1 transporter is composed of two proteins encoded by two distinct genes:

  • 4F2hc/CD98 heavy subunit protein encoded by the SLC3A2 gene (this gene)[6]
  • CD98 light subunit protein encoded by the SLC7A5 gene[7]


SLC3A2 has been shown to interact with SLC7A7.[8]

Additionally, SLC3A2 is a constituent member of the system xc- cystine/glutamate antiporter, complexing with SLC7A11.

See also


  1. Teixeira S, Di Grandi S, Kühn LC (Aug 1987). "Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus". J Biol Chem. 262 (20): 9574–80. PMID 3036867.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. 2.0 2.1 "Entrez Gene: SLC3A2 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2".<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. Kucharzik T, Lugering A, Yan Y, Driss A, Charrier L, Sitaraman S, Merlin D (2005). "Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation". Lab. Invest. 85 (7): 932–41. doi:10.1038/labinvest.3700289. PMID 15880135.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. Lemaître G, Gonnet F, Vaigot P, Gidrol X, Martin MT, Tortajada J, Waksman G (2005). "CD98, a novel marker of transient amplifying human keratinocytes". Proteomics. 5 (14): 3637–45. doi:10.1002/pmic.200401224. PMID 16097038.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. 5.0 5.1 Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM (1999). "Selective expression of the large neutral amino acid transporter at the blood–brain barrier". Proc. Natl. Acad. Sci. U.S.A. 96 (21): 12079–84. doi:10.1073/pnas.96.21.12079. PMC 18415. PMID 10518579.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. Palacín M, Kanai Y (2004). "The ancillary proteins of HATs: SLC3 family of amino acid transporters". Pflügers Arch. 447 (5): 490–494. doi:10.1007/s00424-003-1062-7. PMID 14770309.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y (2004). "CATs and HATs: the SLC7 family of amino acid transporters". Pflügers Arch. 447 (5): 532–542. doi:10.1007/s00424-003-1086-z. PMID 14770310.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. Pfeiffer R, Rossier G, Spindler B, Meier C, Kühn L, Verrey F (Jan 1999). "Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family". EMBO J. 18 (1): 49–57. doi:10.1093/emboj/18.1.49. PMC 1171101. PMID 9878049.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

Further reading

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  • Rochelle JM, Watson ML, Oakey RJ, Seldin MF (1992). "A linkage map of mouse chromosome 19: definition of comparative mapping relationships with human chromosomes 10 and 11 including the MEN1 locus". Genomics. 14 (1): 26–31. doi:10.1016/S0888-7543(05)80278-2. PMID 1358795.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Michalak M, Quackenbush EJ, Letarte M (1986). "Inhibition of Na+/Ca2+ exchanger activity in cardiac and skeletal muscle sarcolemmal vesicles by monoclonal antibody 44D7". J. Biol. Chem. 261 (1): 92–5. PMID 2416754.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Gottesdiener KM, Karpinski BA, Lindsten T, Strominger JL, Jones NH, Thompson CB, Leiden JM (1989). "Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation". Mol. Cell. Biol. 8 (9): 3809–19. PMC 365439. PMID 3265470.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Lindsten T, June CH, Thompson CB, Leiden JM (1989). "Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms". Mol. Cell. Biol. 8 (9): 3820–6. PMC 365440. PMID 3265471.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Quackenbush E, Clabby M, Gottesdiener KM, Barbosa J, Jones NH, Strominger JL, Speck S, Leiden JM (1987). "Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth". Proc. Natl. Acad. Sci. U.S.A. 84 (18): 6526–30. doi:10.1073/pnas.84.18.6526. PMC 299110. PMID 3476959.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Lumadue JA, Glick AB, Ruddle FH (1988). "Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2". Proc. Natl. Acad. Sci. U.S.A. 84 (24): 9204–8. doi:10.1073/pnas.84.24.9204. PMC 299721. PMID 3480538.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Posillico JT, Srikanta S, Eisenbarth G, Quaranta V, Kajiji S, Brown EM (1987). "Binding of monoclonal antibody (4F2) to its cell surface antigen on dispersed adenomatous parathyroid cells raises cytosolic calcium and inhibits parathyroid hormone secretion". J. Clin. Endocrinol. Metab. 64 (1): 43–50. doi:10.1210/jcem-64-1-43. PMID 3782435.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Hemler ME, Strominger JL (1982). "Characterization of antigen recognized by the monoclonal antibody (4F2): different molecular forms on human T and B lymphoblastoid cell lines". J. Immunol. 129 (2): 623–8. PMID 6177771.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Peters PG, Kamarck ME, Hemler ME, Strominger JL, Ruddle FH (1983). "Genetic and biochemical characterization of a human surface determinant on somatic cell hybrids: the 4F2 antigen". Somatic Cell Genet. 8 (6): 825–34. doi:10.1007/BF01543022. PMID 6187076.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Francke U, Foellmer BE, Haynes BF (1983). "Chromosome mapping of human cell surface molecules: monoclonal anti-human lymphocyte antibodies 4F2, A3D8, and A1G3 define antigens controlled by different regions of chromosome 11". Somatic Cell Genet. 9 (3): 333–44. doi:10.1007/BF01539142. PMID 6190235.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Haynes BF, Hemler ME, Mann DL, Eisenbarth GS, Shelhamer J, Mostowski HS, Thomas CA, Strominger JL, Fauci AS (1981). "Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes". J. Immunol. 126 (4): 1409–14. PMID 7204970.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Ohgimoto S, Tabata N, Suga S, Nishio M, Ohta H, Tsurudome M, Komada H, Kawano M, Watanabe N, Ito Y (1995). "Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules". J. Immunol. 155 (7): 3585–92. PMID 7561057.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Ohgimoto S, Tabata N, Suga S, Tsurudome M, Kawano M, Nishio M, Okamoto K, Komada H, Watanabe N, Ito Y (1996). "Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1". J. Gen. Virol. 77 (11): 2747–56. doi:10.1099/0022-1317-77-11-2747. PMID 8922468.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Courseaux A, Grosgeorge J, Gaudray P, Pannett AA, Forbes SA, Williamson C, Bassett D, Thakker RV, Teh BT, Farnebo F, Shepherd J, Skogseid B, Larsson C, Giraud S, Zhang CX, Salandre J, Calender A (1997). "Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1)". Genomics. 37 (3): 354–65. doi:10.1006/geno.1996.0570. PMID 8938448.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Tabata N, Ido M, Suga S, Ohgimoto S, Tsurudome M, Kawano M, Nishio M, Watanabe N, Okamoto K, Komada H, Sakurai M, Ito Y (1998). "Protein tyrosine kinase activation provides an early and obligatory signal in anti-FRP-1/CD98/4F2 monoclonal antibody induced cell fusion mediated by HIV gp160". Med. Microbiol. Immunol. 186 (2–3): 115–23. doi:10.1007/s004300050053. PMID 9403839.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.