View source for Biology:4F2 cell-surface antigen heavy chain

{{Short description|Protein found in humans}}
{{Infobox_gene}}

'''4F2 cell-surface antigen heavy chain'''  is a [[Biology:Protein|protein]] that in humans is encoded by the ''SLC3A2'' (solute carrier family 3 member 2) [[Biology:Gene|gene]].<ref name="pmid3036867">{{cite journal | vauthors = Teixeira S, Di Grandi S, Kühn LC | title = Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus | journal = J Biol Chem | volume = 262 | issue = 20 | pages = 9574–80 | date = Aug 1987 | doi = 10.1016/S0021-9258(18)47972-0 | pmid = 3036867 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC3A2 solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6520}}</ref>

SLC3A2 comprises the heavy subunit of the '''large neutral amino acid transporter''' ('''LAT1''') that is also known as [[Biology:CD98|CD98]] (cluster of differentiation 98).<ref name="pmid15880135">{{cite journal | vauthors = Kucharzik T, Lugering A, Yan Y, Driss A, Charrier L, Sitaraman S, Merlin D | title = Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation | journal = Lab. Invest. | volume = 85 | issue = 7 | pages = 932–41 | year = 2005 | pmid = 15880135 | doi = 10.1038/labinvest.3700289 | s2cid = 19733993 | doi-access =  }}</ref><ref name="pmid16097038">{{cite journal | vauthors = Lemaître G, Gonnet F, Vaigot P, Gidrol X, Martin MT, Tortajada J, Waksman G | title = CD98, a novel marker of transient amplifying human keratinocytes | journal = Proteomics | volume = 5 | issue = 14 | pages = 3637–45 | year = 2005 | pmid = 16097038 | doi = 10.1002/pmic.200401224 | s2cid = 31954787 }}</ref>

== Function ==

SLC3A2 is a member of the [[Biology:Solute carrier family|solute carrier family]] and encodes a cell surface, transmembrane protein with an [[Biology:Alpha-amylase|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.<ref name="entrez" />

LAT1 is a heterodimeric [[Biology:Membrane transport protein|membrane transport protein]] that preferentially transports neutral branched ([[Chemistry:Valine|valine]], [[Chemistry:Leucine|leucine]], [[Chemistry:Isoleucine|isoleucine]]) and aromatic ([[Chemistry:Tryptophan|tryptophan]], [[Chemistry:Tyrosine|tyrosine]], [[Chemistry:Phenylalanine|phenylalanine]]) [[Chemistry:Amino acid|amino acid]]s.<ref name="pmid10518579">{{cite journal | vauthors = Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM | title = Selective expression of the large neutral amino acid transporter at the blood–brain barrier | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 21 | pages = 12079–84 | year = 1999 | pmid = 10518579 | pmc = 18415 | doi = 10.1073/pnas.96.21.12079 | bibcode = 1999PNAS...9612079B | doi-access = free }}</ref> LAT is highly expressed in brain capillaries (which form the blood brain barrier) relative to other tissues.<ref name="pmid10518579" />

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)<ref name="Palacin_2004">{{cite journal | vauthors = Palacín M, Kanai Y | title = The ancillary proteins of HATs: SLC3 family of amino acid transporters | journal = Pflügers Arch | volume = 447 | issue = 5 | pages = 490–494 | year = 2004 | pmid = 14770309 | doi = 10.1007/s00424-003-1062-7 | s2cid = 25808108 }}</ref>
* CD98 light subunit protein encoded by the [[Biology:SLC7A5|SLC7A5]] gene<ref name="Verrey_2004">{{cite journal | vauthors = Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y | title = CATs and HATs: the SLC7 family of amino acid transporters | journal = Pflügers Arch | volume = 447 | issue = 5 | pages = 532–542 | year = 2004 | pmid = 14770310 | doi = 10.1007/s00424-003-1086-z | s2cid = 11670040 | url = http://doc.rero.ch/record/317805/files/424_2003_Article_1086.pdf }}</ref>

== Interactions ==

SLC3A2 has been shown to interact with [[Biology:SLC7A7|SLC7A7]].<ref name=pmid9878049>{{cite journal | vauthors = Pfeiffer R, Rossier G, Spindler B, Meier C, Kühn L, Verrey F | title = Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family | journal = EMBO J. | volume = 18 | issue = 1 | pages = 49–57 | date = Jan 1999 | pmid = 9878049 | pmc = 1171101 | doi = 10.1093/emboj/18.1.49 }}</ref>

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

== See also ==
* Heterodimeric amino acid transporter

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Rochelle JM, Watson ML, Oakey RJ, Seldin MF | title = A linkage map of mouse chromosome 19: definition of comparative mapping relationships with human chromosomes 10 and 11 including the MEN1 locus | journal = Genomics | volume = 14 | issue = 1 | pages = 26–31 | year = 1992 | pmid = 1358795 | doi = 10.1016/S0888-7543(05)80278-2 }}
* {{cite journal | vauthors = Michalak M, Quackenbush EJ, Letarte M | title = Inhibition of Na+/Ca2+ exchanger activity in cardiac and skeletal muscle sarcolemmal vesicles by monoclonal antibody 44D7 | journal = J. Biol. Chem. | volume = 261 | issue = 1 | pages = 92–5 | year = 1986 | doi = 10.1016/S0021-9258(17)42436-7 | pmid = 2416754 | doi-access = free }}
* {{cite journal | vauthors = Gottesdiener KM, Karpinski BA, Lindsten T, Strominger JL, Jones NH, Thompson CB, Leiden JM | title = Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation | journal = Mol. Cell. Biol. | volume = 8 | issue = 9 | pages = 3809–19 | year = 1989 | pmid = 3265470 | pmc = 365439 | doi =  10.1128/mcb.8.9.3809}}
* {{cite journal | vauthors = Lindsten T, June CH, Thompson CB, Leiden JM | title = Regulation of 4F2 heavy-chain gene expression during normal human T-cell activation can be mediated by multiple distinct molecular mechanisms | journal = Mol. Cell. Biol. | volume = 8 | issue = 9 | pages = 3820–6 | year = 1989 | pmid = 3265471 | pmc = 365440 | doi =  10.1128/mcb.8.9.3820}}
* {{cite journal | vauthors = Quackenbush E, Clabby M, Gottesdiener KM, Barbosa J, Jones NH, Strominger JL, Speck S, Leiden JM | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 18 | pages = 6526–30 | year = 1987 | pmid = 3476959 | pmc = 299110 | doi = 10.1073/pnas.84.18.6526 | bibcode = 1987PNAS...84.6526Q | doi-access = free }}
* {{cite journal | vauthors = Lumadue JA, Glick AB, Ruddle FH | title = Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 24 | pages = 9204–8 | year = 1988 | pmid = 3480538 | pmc = 299721 | doi = 10.1073/pnas.84.24.9204 | doi-access = free }}
* {{cite journal | vauthors = Posillico JT, Srikanta S, Eisenbarth G, Quaranta V, Kajiji S, Brown EM | title = Binding of monoclonal antibody (4F2) to its cell surface antigen on dispersed adenomatous parathyroid cells raises cytosolic calcium and inhibits parathyroid hormone secretion | journal = J. Clin. Endocrinol. Metab. | volume = 64 | issue = 1 | pages = 43–50 | year = 1987 | pmid = 3782435 | doi = 10.1210/jcem-64-1-43 }}
* {{cite journal | vauthors = Hemler ME, Strominger JL | title = Characterization of antigen recognized by the monoclonal antibody (4F2): different molecular forms on human T and B lymphoblastoid cell lines | journal = J. Immunol. | volume = 129 | issue = 2 | pages = 623–8 | year = 1982 | doi = 10.4049/jimmunol.129.2.623 | pmid = 6177771 | s2cid = 42283583 | doi-access = free }}
* {{cite journal | vauthors = Peters PG, Kamarck ME, Hemler ME, Strominger JL, Ruddle FH | title = Genetic and biochemical characterization of a human surface determinant on somatic cell hybrids: the 4F2 antigen | journal = Somatic Cell Genet | volume = 8 | issue = 6 | pages = 825–34 | year = 1983 | pmid = 6187076 | doi = 10.1007/BF01543022 | s2cid = 19788137 }}
* {{cite journal | vauthors = Francke U, Foellmer BE, Haynes BF | title = 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 | journal = Somatic Cell Genet | volume = 9 | issue = 3 | pages = 333–44 | year = 1983 | pmid = 6190235 | doi = 10.1007/BF01539142 | s2cid = 22972681 }}
* {{cite journal | vauthors = Haynes BF, Hemler ME, Mann DL, Eisenbarth GS, Shelhamer J, Mostowski HS, Thomas CA, Strominger JL, Fauci AS | title = Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes | journal = J. Immunol. | volume = 126 | issue = 4 | pages = 1409–14 | year = 1981 | doi = 10.4049/jimmunol.126.4.1409 | pmid = 7204970 | s2cid = 42367568 | doi-access = free }}
* {{cite journal | vauthors = Ohgimoto S, Tabata N, Suga S, Nishio M, Ohta H, Tsurudome M, Komada H, Kawano M, Watanabe N, Ito Y | title = 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 | journal = J. Immunol. | volume = 155 | issue = 7 | pages = 3585–92 | year = 1995 | doi = 10.4049/jimmunol.155.7.3585 | pmid = 7561057 | s2cid = 8787778 | doi-access = free }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Anal. Biochem. | volume = 236 | issue = 1 | pages = 107–13 | year = 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
* {{cite journal | vauthors = Ohgimoto S, Tabata N, Suga S, Tsurudome M, Kawano M, Nishio M, Okamoto K, Komada H, Watanabe N, Ito Y | title = Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1 | journal = J. Gen. Virol. | volume = 77 | issue = 11 | pages = 2747–56 | year = 1996 | pmid = 8922468 | doi = 10.1099/0022-1317-77-11-2747 | doi-access =  }}
* {{cite journal | vauthors = 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 | title = 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) | journal = Genomics | volume = 37 | issue = 3 | pages = 354–65 | year = 1997 | pmid = 8938448 | doi = 10.1006/geno.1996.0570 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-Scale Concatenation cDNA Sequencing | journal = Genome Res. | volume = 7 | issue = 4 | pages = 353–8 | year = 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Tabata N, Ido M, Suga S, Ohgimoto S, Tsurudome M, Kawano M, Nishio M, Watanabe N, Okamoto K, Komada H, Sakurai M, Ito Y | title = 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 | journal = Med. Microbiol. Immunol. | volume = 186 | issue = 2–3 | pages = 115–23 | year = 1998 | pmid = 9403839 | doi = 10.1007/s004300050053 | s2cid = 7693336 }}
{{refend}}

== External links ==
* {{MeshName|Large+Neutral+Amino+Acid-Transporter+1}}
* {{MeshName|Amino+Acid+Transport+System+L}}

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{{PDB Gallery|geneid=6520}}


[[Category:Solute carrier family]]

{{Sourceattribution|4F2 cell-surface antigen heavy chain}}