SLC3A2

Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2
PDB rendering based on 2dh2.
Available structures PDB 2DH2, 2DH3
Identifiers
Symbols	SLC3A2; 4F2; 4F2HC; 4T2HC; CD98; CD98HC; MDU1; NACAE
External IDs	OMIM: 158070 MGI: 96955 HomoloGene: 1795 GeneCards: SLC3A2 Gene
Gene Ontology Molecular function • catalytic activity • calcium:sodium antiporter activity • protein binding • neutral amino acid transmembrane transporter activity • cation binding Cellular component • plasma membrane • plasma membrane • cell surface • integral to membrane • apical plasma membrane • melanosome Biological process • carbohydrate metabolic process • ion transport • calcium ion transport • amino acid transport • amino acid transport • blood coagulation • tryptophan transport • cell growth • cellular nitrogen compound metabolic process • leukocyte migration • transmembrane transport • leucine import Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6520	17254
Ensembl	ENSG00000168003	ENSMUSG00000010095
UniProt	P08195	Q3TIP1
RefSeq (mRNA)	NM_001012661.1	NM_008577
RefSeq (protein)	NP_001012679.1	NP_032603
Location (UCSC)	Chr 11: 62.62 – 62.66 Mb	Chr 19: 8.78 – 8.8 Mb
PubMed search	[1]	[2]

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

Function

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]

Interactions

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

See also

• Heterodimeric amino acid transporter

References

1. ^ Teixeira S, Di Grandi S, Kuhn 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. 
2. ^ ^{a b} "Entrez Gene: SLC3A2 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6520. 
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. 
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. 
5. ^ ^{a b} 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18415. 
6. ^ Palacin M, Kanai Y (2004). "The ancillary proteins of HATs: SLC3 family of amino acid transporters". Pflugers Arch 447 (5): 490–494. doi:10.1007/s00424-003-1062-7. PMID 14770309. 
7. ^ Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y (2004). "CATs and HATs: the SLC7 family of amino acid transporters". Pflugers Arch 447 (5): 532–542. doi:10.1007/s00424-003-1086-z. PMID 14770310. 
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. (ENGLAND) 18 (1): 49–57. doi:10.1093/emboj/18.1.49. ISSN 0261-4189. PMC 1171101. PMID 9878049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171101. 

Further reading

• 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. 
• 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. 
• Gottesdiener KM, Karpinski BA, Lindsten T et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=365439. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=365440. 
• Quackenbush E, Clabby M, Gottesdiener KM et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299110. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299721. 
• Posillico JT, Srikanta S, Eisenbarth G et al. (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. 
• 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. 
• Peters PG, Kamarck ME, Hemler ME et al. (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. 
• 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. 
• Haynes BF, Hemler ME, Mann DL et al. (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. 
• Ohgimoto S, Tabata N, Suga S et al. (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. 
• 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. 
• Andersson B, Wentland MA, Ricafrente JY et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
• Ohgimoto S, Tabata N, Suga S et al. (1996). "Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1". J. Gen. Virol. 77 ( Pt 11) (11): 2747–56. doi:10.1099/0022-1317-77-11-2747. PMID 8922468. 
• Courseaux A, Grosgeorge J, Gaudray P et al. (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. PMID 8938448. 
• Yu W, Andersson B, Worley KC et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139146. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (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. 
• Tabata N, Ido M, Suga S et al. (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. 

External links

• MeSH Large+Neutral+Amino+Acid-Transporter+1
• MeSH Amino+Acid+Transport+System+L

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

2dh3: Crystal Structure of human ED-4F2hc