Gene Symbol: Slc3a2
Description: solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2
Alias: 4F2, 4F2HC, AI314110, Cd98, Ly-10, Ly-m10, Ly10, Mdu1, Mgp-2hc, NACAE, 4F2 cell-surface antigen heavy chain, CD98 antigen, CD98 heavy chain, antigen identified by monoclonal antibodies 4F2, solute carrier family 3 member 2, type II transmembrane protein
Species: mouse
Products:     Slc3a2

Top Publications

  1. Nguyen H, Dalmasso G, Torkvist L, Halfvarson J, Yan Y, Laroui H, et al. CD98 expression modulates intestinal homeostasis, inflammation, and colitis-associated cancer in mice. J Clin Invest. 2011;121:1733-47 pubmed publisher
    Expression of the transmembrane glycoprotein CD98 (encoded by SLC3A2) is increased in intestinal inflammatory conditions, such as inflammatory bowel disease (IBD), and in various carcinomas, yet its pathogenetic role remains unknown...
  2. Fogelstrand P, Feral C, Zargham R, Ginsberg M. Dependence of proliferative vascular smooth muscle cells on CD98hc (4F2hc, SLC3A2). J Exp Med. 2009;206:2397-406 pubmed publisher
    ..We show that CD98 heavy chain (CD98hc) is markedly up-regulated in neointimal and cultured VSMCs, and that activated but not quiescent ..
  3. Cantor J, Browne C, Ruppert R, Feral C, Fassler R, Rickert R, et al. CD98hc facilitates B cell proliferation and adaptive humoral immunity. Nat Immunol. 2009;10:412-9 pubmed publisher
    ..We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent ..
  4. Feral C, Zijlstra A, Tkachenko E, Prager G, Gardel M, Slepak M, et al. CD98hc (SLC3A2) participates in fibronectin matrix assembly by mediating integrin signaling. J Cell Biol. 2007;178:701-11 pubmed
    ..CD98hc expression can vary widely; our data show that these variations in CD98hc expression can control the capacity of cells to assemble an Fn matrix, a process important in development, wound healing, and tumorigenesis. ..
  5. Feral C, Nishiya N, Fenczik C, Stuhlmann H, Slepak M, Ginsberg M. CD98hc (SLC3A2) mediates integrin signaling. Proc Natl Acad Sci U S A. 2005;102:355-60 pubmed
    ..CD98 heterodimers, comprised of a heavy chain (CD98hc, SLC3A2) and one of several light chains, interact with integrins through CD98hc...
  6. Fukasawa Y, Segawa H, Kim J, Chairoungdua A, Kim D, Matsuo H, et al. Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids. J Biol Chem. 2000;275:9690-8 pubmed
    ..and b(0,+), which are linked, via a disulfide bond, to the type II membrane glycoproteins, 4F2 heavy chain (4F2hc), or rBAT (related to b(0,+) amino acid transporter). Asc-1 required 4F2hc for its functional expression...
  7. Prager G, Feral C, Kim C, Han J, Ginsberg M. CD98hc (SLC3A2) interaction with the integrin beta subunit cytoplasmic domain mediates adhesive signaling. J Biol Chem. 2007;282:24477-84 pubmed
    ..physically associates with certain integrin beta subunit cytoplasmic domains (tails) via its heavy chain, CD98hc (SLC3A2), and loss of CD98hc impairs integrin signaling...
  8. Cai S, Bulus N, Fonseca Siesser P, Chen D, Hanks S, Pozzi A, et al. CD98 modulates integrin beta1 function in polarized epithelial cells. J Cell Sci. 2005;118:889-99 pubmed
    The type II transmembrane protein CD98, best known as the heavy chain of the heterodimeric amino acid transporters (HAT), is required for the surface expression and basolateral localization of this transporter complex in polarized ..
  9. Tsumura H, Suzuki N, Saito H, Kawano M, Otake S, Kozuka Y, et al. The targeted disruption of the CD98 gene results in embryonic lethality. Biochem Biophys Res Commun. 2003;308:847-51 pubmed
    ..In this study, CD98 heavy chain (HC) knockout mice were produced and analyzed...

More Information


  1. Nakamura E, Sato M, Yang H, Miyagawa F, Harasaki M, Tomita K, et al. 4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer. J Biol Chem. 1999;274:3009-16 pubmed
    4F2, also termed CD98, is an integral membrane protein consisting of a heavy chain linked to a light chain by disulfide bond. We have generated a monoclonal antibody to the mouse 4F2 light chain and cloned the cDNA...
  2. Ohgaki R, Ohmori T, Hara S, Nakagomi S, Kanai Azuma M, Kaneda Nakashima K, et al. Essential Roles of L-Type Amino Acid Transporter 1 in Syncytiotrophoblast Development by Presenting Fusogenic 4F2hc. Mol Cell Biol. 2017;37: pubmed publisher
    ..L-type amino acid transporter 1 (LAT1) and its covalently linked ancillary subunit 4F2hc are colocalized on both maternal and fetal surfaces of syncytiotrophoblasts, implying their roles in amino acid ..
  3. Estrach S, Lee S, Boulter E, Pisano S, Errante A, Tissot F, et al. CD98hc (SLC3A2) loss protects against ras-driven tumorigenesis by modulating integrin-mediated mechanotransduction. Cancer Res. 2014;74:6878-89 pubmed publisher
    CD98hc (SLC3A2) is the heavy chain component of the dimeric transmembrane glycoprotein CD98, which comprises the large neutral amino acid transporter LAT1 (SLC7A5) in cells...
  4. Devereux T, Wiseman R, Kaplan N, Garren S, Foley J, White C, et al. Assignment of a locus for mouse lung tumor susceptibility to proximal chromosome 19. Mamm Genome. 1994;5:749-55 pubmed
    ..Linkage analysis on Chr 19 with 270 AB6N2 mice localized the region flanked by D19Mit42 and D19Mit19 that is most closely associated with lung tumor susceptibility. The Pas3 locus may be an enhancer of the susceptibility locus on Chr 6. ..
  5. Tsumura H, Ito M, Li X, Nakamura A, Ohnami N, Fujimoto J, et al. The role of CD98hc in mouse macrophage functions. Cell Immunol. 2012;276:128-34 pubmed publisher
    CD98hc is a type II transmembrane protein that covalently links to one of several L-type amino acid transporters. CD98hc was first identified as a lymphocyte activation marker...
  6. Fowler K, Clouston W, Fournier R, Evans B. The relaxin gene is located on chromosome 19 in the mouse. FEBS Lett. 1991;292:183-6 pubmed
    ..The finding of a BamHI restriction fragment length polymorphism in AKR mice enabled us to use recombinant inbred strains to make an assignment to chromosome 19. This was confirmed by Southern analysis of DNA from microcell hybrids. ..
  7. Kakugawa K, Hattori M, Beauchemin N, Minato N. Activation of CEA-CAM-1-mediated cell adhesion via CD98: involvement of PKCdelta. FEBS Lett. 2003;552:184-8 pubmed
    b>CD98 is a multifunctional protein involved in amino acid transport and regulation of integrin-mediated cell adhesion...
  8. Cantor J. CD98 is a potential target for ablating B cell clonal expansion and autoantibody in multiple sclerosis. J Neuroimmunol. 2014;274:230-3 pubmed publisher
    ..Mice lacking CD98hc in B cells are protected from EAE; importantly this is overcome with autoantibody-containing plasma. Thus CD98hc blockade is a possible avenue to treat MS by inhibiting clonal expansion and autoantibody. ..
  9. Horlick K, Cheng I, Wong W, Wakeland E, Nick H. Mouse lipocortin I gene structure and chromosomal assignment: gene duplication and the origins of a gene family. Genomics. 1991;10:365-74 pubmed
    ..This pattern supports the gene duplication theory, and the similarity in gene structure between mouse Lipo I and Lipo II suggests they have a recent evolutionary ancestor. ..
  10. Ramadan T, Camargo S, Herzog B, Bordin M, Pos K, Verrey F. Recycling of aromatic amino acids via TAT1 allows efflux of neutral amino acids via LAT2-4F2hc exchanger. Pflugers Arch. 2007;454:507-16 pubmed
    ..Because LAT2-4F2hc (Slc7a8-Slc3a2), the best known basolateral neutral amino acid transporter of these epithelial cells, functions as an obligatory ..
  11. Kucharzik T, Lugering A, Yan Y, Driss A, Charrier L, Sitaraman S, et al. Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation. Lab Invest. 2005;85:932-41 pubmed
    ..Several classes of cell surface glycoproteins such as CD98 have been shown to play roles in integrins-mediated events...
  12. Hunter K, Broman K, Voyer T, Lukes L, Cozma D, Debies M, et al. Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res. 2001;61:8866-72 pubmed
    ..Interestingly, Mtes1 colocalizes with the murine orthologue of the human breast cancer metastasis suppressor gene Brms1, suggesting that allelic variants of Brms1 might be responsible for the metastasis suppression observed. ..
  13. Wada Y, Kubota H, Maeda M, Taniwaki M, Hattori M, Imamura S, et al. Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human. Genomics. 1997;39:66-73 pubmed
    ..3 subregion. It was further indicated by double-color FISH that SIPA1 was located in the centromeric neighborhood of CCND1/ PRAD1, a presumed BCL1 oncogene. ..
  14. Nguyen H, Dalmasso G, Yan Y, Laroui H, Charania M, Ingersoll S, et al. Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in Apc(Min/+) mice. Lab Invest. 2012;92:1203-12 pubmed publisher
    The transmembrane glycoprotein CD98 regulates integrin signaling that in turn controls cell proliferation and survival. CD98 expression is upregulated in various carcinomas, including colorectal cancer...
  15. Bajaj J, Konuma T, Lytle N, Kwon H, Ablack J, Cantor J, et al. CD98-Mediated Adhesive Signaling Enables the Establishment and Propagation of Acute Myelogenous Leukemia. Cancer Cell. 2016;30:792-805 pubmed publisher
    ..Here we show that the integrin binding glycoprotein CD98 plays a central role in AML...
  16. Charania M, Ayyadurai S, Ingersoll S, Xiao B, Viennois E, Yan Y, et al. Intestinal epithelial CD98 synthesis specifically modulates expression of colonic microRNAs during colitis. Am J Physiol Gastrointest Liver Physiol. 2012;302:G1282-91 pubmed publisher
    The transmembrane glycoprotein CD98 is known to be involved in intestinal inflammation...
  17. Fernandes M, Lespinasse F, Rotomondo F, Poirier C, Guenet J, Gaudray P, et al. Comparative mapping of two adjacent regions of MMU19 with their human counterpart on HSA11q13. Cytogenet Cell Genet. 1998;81:237-46 pubmed
    ..5-Mb region. Strikingly, the 0.5-Mb region has a similar size in human but gene order is shuffled. The overall comparative map shows that these two regions are inverted on MMU19 when compared with HSA11q13. ..
  18. Parmacek M, Karpinski B, Gottesdiener K, Thompson C, Leiden J. Structure, expression and regulation of the murine 4F2 heavy chain. Nucleic Acids Res. 1989;17:1915-31 pubmed
    ..To elucidate the structure, expression, and regulation of the 4F2 molecule, a murine 4F2 heavy chain (4F2HC) cDNA has been isolated and structurally characterized...
  19. Sekine M, Nara K, Suzuki A. Tissue-specific regulation of mouse core 2 beta-1,6-N-acetylglucosaminyltransferase. J Biol Chem. 1997;272:27246-52 pubmed
    ..These data suggest that the expression of GNT is regulated by an alternative splicing mechanism and also probably by tissue-specific enhancers and that Gsl5 regulates the expression of GNT only in the kidney. ..
  20. Baumer Y, McCurdy S, Alcala M, Mehta N, Lee B, Ginsberg M, et al. CD98 regulates vascular smooth muscle cell proliferation in atherosclerosis. Atherosclerosis. 2017;256:105-114 pubmed publisher
    ..CD98 is a transmembrane protein made of two subunits, CD98 heavy chain (CD98hc) and one of six light chains, and is known to be involved in cell proliferation and survival...
  21. Liao Z, Cantor J. Endothelial Cells Require CD98 for Efficient Angiogenesis-Brief Report. Arterioscler Thromb Vasc Biol. 2016;36:2163-2166 pubmed
    b>CD98 regulates integrin signaling and is critical for tumor cell proliferation. It is also expressed on endothelial cells (EC), but its role in angiogenesis is unclear...
  22. Ablack J, Metz P, Chang J, Cantor J, Ginsberg M. Ubiquitylation of CD98 limits cell proliferation and clonal expansion. J Cell Sci. 2015;128:4273-8 pubmed publisher
    b>CD98 heavy chain (SLC3A2) facilitates lymphocyte clonal expansion that enables adaptive immunity; however, increased expression of CD98 is also a feature of both lymphomas and leukemias and represents a potential therapeutic target in ..
  23. Levanon D, Hsieh C, Francke U, Dawson P, Ridgway N, Brown M, et al. cDNA cloning of human oxysterol-binding protein and localization of the gene to human chromosome 11 and mouse chromosome 19. Genomics. 1990;7:65-74 pubmed
    ..Along with previously mapped genes including Ly-1 and CD20, OSBP defines a new conserved syntenic group on the long arm of chromosome 11 in the human and the proximal end of chromosome 19 in the mouse. ..
  24. Burdo J, Dargusch R, Schubert D. Distribution of the cystine/glutamate antiporter system xc- in the brain, kidney, and duodenum. J Histochem Cytochem. 2006;54:549-57 pubmed
    ..main transporters responsible for central nervous system cystine transport, is comprised of two subunits, xCT and 4F2hc. The transport of cystine into cells is rate limiting for glutathione synthesis, the major antioxidant and redox ..
  25. Tsumura H, Kawano M, Tajima M, Kusaura T, Kozuka Y, Yoshimura S, et al. Isolation and characterization of monoclonal antibodies directed against murine FRP-1/CD98/4F2 heavy chain: murine FRP-1 is an alloantigen and amino acid change at 129 (P<-->R) is related to the alloantigenicity. Immunol Cell Biol. 1999;77:19-27 pubmed
    Nineteen mAb directed against murine fusion regulatory protein-1 (mFRP-1)/4F2/CD98 were isolated and their biological properties were analysed. Intriguingly, mFRP-1 was found to be an alloantigen, namely, FRP-1...
  26. Yoder J, Litman G. The zebrafish fth1, slc3a2, men1, pc, fgf3 and cycd1 genes define two regions of conserved synteny between linkage group 7 and human chromosome 11q13. Gene. 2000;261:235-42 pubmed
    ..In an effort to further define this relationship, five full-length zebrafish cDNAs, fth1, slc3a2, prkri, cd81, and pc, as well as one putative human gene, DBX were identified and their map positions ascertained...
  27. Sato H, Nomura S, Maebara K, Sato K, Tamba M, Bannai S. Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation. Biochem Biophys Res Commun. 2004;325:109-16 pubmed
    ..This transporter is composed of two protein components, xCT and 4F2 heavy chain, and xCT is thought to mediate the transport activity...
  28. de la Ballina L, Cano Crespo S, González Muñoz E, Bial S, Estrach S, Cailleteau L, et al. Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability. J Biol Chem. 2016;291:9700-11 pubmed publisher
    ..Our data establish CD98hc as a master protective gene at the cross-road of redox control and AA availability, making it a relevant therapeutic target in cancer. ..
  29. Warren A, Patel K, McConkey D, Palacios R. CD98: a type II transmembrane glycoprotein expressed from the beginning of primitive and definitive hematopoiesis may play a critical role in the development of hematopoietic cells. Blood. 1996;87:3676-87 pubmed
    ..Molecular cloning and expression indicated that Joro 177 MoAb recognizes a type II transmembrane protein, which is the mouse homologue of the human CD98 heavy chain gene...
  30. Kimura S, Tada N, Liu Lam Y, Hammerling U. Further genetic characterization of mouse Ly-m10 alloantigen. Immunogenetics. 1983;17:211-4 pubmed
  31. Floyd J, Gold D, Concepcion D, Poon T, Wang X, Keithley E, et al. A natural allele of Nxf1 suppresses retrovirus insertional mutations. Nat Genet. 2003;35:221-8 pubmed
    ..A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements. ..
  32. Quackenbush E, Clabby M, Gottesdiener K, Barbosa J, Jones N, Strominger J, et al. 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. 1987;84:6526-30 pubmed
    Complementary DNA (cDNA) clones encoding the heavy chain of the heterodimeric human membrane glycoprotein 4F2 have been isolated by immunoscreening of a lambda gt11 expression library...
  33. Uemura T, Stringer D, Blohm Mangone K, Gerner E. Polyamine transport is mediated by both endocytic and solute carrier transport mechanisms in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2010;299:G517-22 pubmed publisher
    ..Knocking down the solute carrier transporter SLC3A2 in HCT116-derived Hkh2 cells reduced the accumulation of exogenous putrescine and total polyamine contents in DFMO ..
  34. Chainani M, Sampsell B, Elliott R. Localization of the gene for plasma retinol binding protein to the distal half of mouse chromosome 19. Genomics. 1991;9:376-9 pubmed
    ..The Rbp-4 locus is just proximal to Cyp-2c at the distal end of chromosome 19. ..
  35. Hupp K, Siwarski D, Mock B, Kinet J. Gene mapping of the three subunits of the high affinity FcR for IgE to mouse chromosomes 1 and 19. J Immunol. 1989;143:3787-91 pubmed
    ..The close association of the genes for Fc epsilon RI alpha, FC gamma RII, and their shared gamma subunits raises interesting implications regarding coordinate regulation of gene expression. ..
  36. Hogarth P, Houlden B, Latham S, Cherry M, Taylor B, McKenzie I. The mouse Ly-12.1 specificity: genetic and biochemical relationship to Ly-1. Immunogenetics. 1988;27:383-7 pubmed
  37. Bulus N, Feral C, Pozzi A, Zent R. CD98 increases renal epithelial cell proliferation by activating MAPKs. PLoS ONE. 2012;7:e40026 pubmed publisher
    b>CD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs)...
  38. Broer S, Bröer A, Hamprecht B. The 4F2hc surface antigen is necessary for expression of system L-like neutral amino acid-transport activity in C6-BU-1 rat glioma cells: evidence from expression studies in Xenopus laevis oocytes. Biochem J. 1995;312 ( Pt 3):863-70 pubmed
    ..Sequencing of the cDNA showed that the identified clone is the heavy chain of the rat 4F2 surface antigen, a marker of tumour cells and activated lymphocytes...
  39. Nishio Y, Fujino M, Cai S, Kitajima Y, Saito T, Tsumura H, et al. Impaired CD98 signaling protects against graft-versus-host disease by increasing regulatory T cells. Transpl Immunol. 2016;35:34-9 pubmed publisher
    ..A murine model of C57BL/6 to B6D2F1 acute GvHD was employed with T lymphocytes harboring a deletion of the CD98 heavy chain (CD98hc(-/-)) as donor cells...
  40. Inglis J, Lee M, Hill R. Emk, a protein kinase with homologs in yeast maps to mouse chromosome 19. Mamm Genome. 1993;4:401-3 pubmed
  41. Bhuyan Z, Arimochi H, Nishida J, Kataoka K, Kurihara T, Ishifune C, et al. CD98hc regulates the development of experimental colitis by controlling effector and regulatory CD4(+) T cells. Biochem Biophys Res Commun. 2014;444:628-33 pubmed publisher
    ..In this study, we investigated how the CD98 heavy chain (CD98hc, Slc3a2) affected the development of colitis in an experimental animal model...
  42. Komada H, Imai A, Hattori E, Ito M, Tsumura H, Onoda T, et al. Possible activation of murine T lymphocyte through CD98 is independent of interleukin 2/interleukin 2 receptor system. Biomed Res. 2006;27:61-7 pubmed
    ..Monoclonal antibody (mAb) directed against murine CD98 heavy chain (mCD98HC) suppressed the proliferation of lymphocytes stimulated with concanavalin A (Con A)...
  43. Tada N, Kimura S, Hammerling U. Immunogenetics of mouse B-cell alloantigen systems defined by monoclonal antibodies and gene-cluster formation of these loci. Immunol Rev. 1982;69:99-126 pubmed
  44. Li X, Yin W, Perez Jurado L, Bonadio J, Francke U. Mapping of human and murine genes for latent TGF-beta binding protein-2 (LTBP2). Mamm Genome. 1995;6:42-5 pubmed
    ..Analysis of BXD and AKXL recombinant inbred strains have placed Ltbp2 between D19Rp19 and Ly10 on proximal mouse Chr 19.
  45. Boulter E, Estrach S, Errante A, Pons C, Cailleteau L, Tissot F, et al. CD98hc (SLC3A2) regulation of skin homeostasis wanes with age. J Exp Med. 2013;210:173-90 pubmed publisher
    ..This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro...
  46. Liu Z, Hou J, Chen J, Tsumura H, Ito M, Ito Y, et al. Deletion of CD98 heavy chain in T cells results in cardiac allograft acceptance by increasing regulatory T cells. Transplantation. 2012;93:1116-24 pubmed publisher
    Little is known about the CD98 heavy chain (CD98hc) in the T lymphocyte-mediated immune response to alloantigen...
  47. Cantor J, Slepak M, Ege N, Chang J, Ginsberg M. Loss of T cell CD98 H chain specifically ablates T cell clonal expansion and protects from autoimmunity. J Immunol. 2011;187:851-60 pubmed publisher
    CD98 H chain (4F2 Ag, Slc3a2) was discovered as a lymphocyte-activation Ag. Deletion of CD98 H chain in B cells leads to complete failure of B cell proliferation, plasma cell formation, and Ab secretion...
  48. Guida L, Charlton P, Gilbert D, Jenkins N, Copeland N, Nicholls R. Genetic mapping of the galanin-GMAP (Galn) gene to mouse chromosome 19. Mamm Genome. 1998;9:240-2 pubmed
  49. Rochelle J, Watson M, Oakey R, Seldin M. A linkage map of mouse chromosome 19: definition of comparative mapping relationships with human chromosomes 10 and 11 including the MEN1 locus. Genomics. 1992;14:26-31 pubmed