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8.A.9.2.2
The Slc3A2 (CD98hc; 4F2hc) accessory protein facilitates transport of amino acids and polyamines (putrescine/spermidine) (Uemura et al. 2008). 4F2hc stabilizes GLUT1 (2.A.1.1.28) and increase glucose transport activity (Ohno et al., 2011).  It forms a heterodimer with glycoprotein CD98 (LAT1; SLC7A5).  It contributes to tumorigenesis (Estrach et al. 2014).  CD98hc also modulates integrin signaling, plays a role in cell-to-cell fusion, and is essential for Brucella infection (Keriel et al. 2015). Hepatitis C virus (HCV) exploits SLC3A2 for viral propagation, and upregulation of SLC3A2 may contribute to HCV-mediated pathogenesis (Nguyen et al. 2018). ZEB1, a transcriptional repressor (P37275), promotes chemoresistance to cisplatin in ovarian cancer cells by suppressing SLC3A2 (Cui et al. 2018).

Accession Number:P08195
Protein Name:4F2 cell-surface antigen heavy chain
Length:630
Molecular Weight:67994.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Apical cell membrane1 / Single-pass type II membrane protein2
Substrate NONE

Cross database links:

Genevestigator: P08195 P08195
eggNOG: prNOG12807 COG0366
HEGENOM: HBG714831 HOG000233529
RefSeq: NP_001012679.1    NP_001012680.1    NP_001012681.1    NP_001012682.1    NP_001013269.1    NP_002385.3   
Entrez Gene ID: 6520   
Pfam: PF00128   
OMIM: 158070  gene
BioCyc: MetaCyc:MONOMER-15188   
KEGG: hsa:6520    hsa:6520   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0009986 C:cell surface
GO:0016021 C:integral to membrane
GO:0042470 C:melanosome
GO:0005432 F:calcium:sodium antiporter activity
GO:0003824 F:catalytic activity
GO:0043169 F:cation binding
GO:0015175 F:neutral amino acid transmembrane transporte...
GO:0005515 F:protein binding
GO:0006816 P:calcium ion transport
GO:0005975 P:carbohydrate metabolic process
GO:0016049 P:cell growth
GO:0060356 P:leucine import
GO:0015827 P:tryptophan transport
GO:0005886 C:plasma membrane
GO:0015175 F:neutral amino acid transmembrane transporter activity
GO:0007596 P:blood coagulation
GO:0050900 P:leukocyte migration

References (71)

[1] “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.”  Quackenbush E.et.al.   3476959
[2] “Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus.”  Teixeira S.et.al.   3036867
[3] “Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2.”  Lumadue J.A.et.al.   3480538
[4] “Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.”  Gottesdiener K.M.et.al.   3265470
[5] “Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.”  Yanagida O.et.al.   11557028
[6] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance.”  Torrents D.et.al.   9829974
[9] “Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.”  Mastroberardino L.et.al.   9751058
[10] “Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.”  Pfeiffer R.et.al.   9878049
[11] “The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine.”  Broeer A.et.al.   10903140
[12] “Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains.”  Broeer A.et.al.   11311135
[13] “Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta.”  Ritchie J.W.A.et.al.   11389679
[14] “Beta1 integrins show specific association with CD98 protein in low density membranes.”  Kolesnikova T.V.et.al.   11696247
[15] “Thyroid hormone transport by the heterodimeric human system L amino acid transporter.”  Friesema E.C.H.et.al.   11564694
[16] “Expression and regulation of 4F2hc and hLAT1 in human trophoblasts.”  Okamoto Y.et.al.   11742812
[17] “Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism.”  He X.H.et.al.   12270127
[18] “Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2.”  Simmons-Willis T.A.et.al.   12117417
[19] “Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells.”  Kim D.K.et.al.   12225859
[20] “Cluster analysis of an extensive human breast cancer cell line protein expression map database.”  Harris R.A.et.al.   11840567
[21] “Nitric oxide synthesis requires activity of the cationic and neutral amino acid transport system y+L in human umbilical vein endothelium.”  Arancibia-Garavilla Y.et.al.   14603368
[22] “CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia.”  Liu X.et.al.   12716892
[23] “Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.”  Zhang H.et.al.   12754519
[24] “L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier.”  Tomi M.et.al.   15980244
[25] “Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols.”  Li S.et.al.   15769744
[26] “Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.”  Liu T.et.al.   16335952
[27] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[28] “L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors.”  Nawashiro H.et.al.   16496379
[29] “Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.”  Chi A.et.al.   17081065
[30] “Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry.”  Meierhofer D.et.al.   18781797
[31] “Ecto-phosphorylation of CD98 regulates cell-cell interactions.”  Nguyen H.T.T.et.al.   19065266
[32] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218
[33] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973
[34] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[35] “The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane.”  Fort J.et.al.   17724034
[36] “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.”  Quackenbush E.et.al.   3476959
[37] “Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus.”  Teixeira S.et.al.   3036867
[38] “Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2.”  Lumadue J.A.et.al.   3480538
[39] “Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.”  Gottesdiener K.M.et.al.   3265470
[40] “Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.”  Yanagida O.et.al.   11557028
[41] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[42] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[43] “Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance.”  Torrents D.et.al.   9829974
[44] “Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.”  Mastroberardino L.et.al.   9751058
[45] “Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.”  Pfeiffer R.et.al.   9878049
[46] “The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine.”  Broeer A.et.al.   10903140
[47] “Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains.”  Broeer A.et.al.   11311135
[48] “Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta.”  Ritchie J.W.A.et.al.   11389679
[49] “Beta1 integrins show specific association with CD98 protein in low density membranes.”  Kolesnikova T.V.et.al.   11696247
[50] “Thyroid hormone transport by the heterodimeric human system L amino acid transporter.”  Friesema E.C.H.et.al.   11564694
[51] “Expression and regulation of 4F2hc and hLAT1 in human trophoblasts.”  Okamoto Y.et.al.   11742812
[52] “Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism.”  He X.H.et.al.   12270127
[53] “Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2.”  Simmons-Willis T.A.et.al.   12117417
[54] “Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells.”  Kim D.K.et.al.   12225859
[55] “Cluster analysis of an extensive human breast cancer cell line protein expression map database.”  Harris R.A.et.al.   11840567
[56] “Nitric oxide synthesis requires activity of the cationic and neutral amino acid transport system y+L in human umbilical vein endothelium.”  Arancibia-Garavilla Y.et.al.   14603368
[57] “CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia.”  Liu X.et.al.   12716892
[58] “Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.”  Zhang H.et.al.   12754519
[59] “L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier.”  Tomi M.et.al.   15980244
[60] “Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols.”  Li S.et.al.   15769744
[61] “Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.”  Liu T.et.al.   16335952
[62] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[63] “L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors.”  Nawashiro H.et.al.   16496379
[64] “Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.”  Chi A.et.al.   17081065
[65] “Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry.”  Meierhofer D.et.al.   18781797
[66] “Ecto-phosphorylation of CD98 regulates cell-cell interactions.”  Nguyen H.T.T.et.al.   19065266
[67] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218
[68] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973
[69] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[70] “Initial characterization of the human central proteome.”  Burkard T.R.et.al.   21269460
[71] “The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane.”  Fort J.et.al.   17724034
Structure:
2DH2   2DH3     

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE LLASGDPLPS 
61:	ASQNAEMIET GSDCVTQAGL QLLASSDPPA LASKNAEVTG TMSQDTEVDM KEVELNELEP 
121:	EKQPMNAASG AAMSLAGAEK NGLVKIKVAE DEAEAAAAAK FTGLSKEELL KVAGSPGWVR 
181:	TRWALLLLFW LGWLGMLAGA VVIIVRAPRC RELPAQKWWH TGALYRIGDL QAFQGHGAGN 
241:	LAGLKGRLDY LSSLKVKGLV LGPIHKNQKD DVAQTDLLQI DPNFGSKEDF DSLLQSAKKK 
301:	SIRVILDLTP NYRGENSWFS TQVDTVATKV KDALEFWLQA GVDGFQVRDI ENLKDASSFL 
361:	AEWQNITKGF SEDRLLIAGT NSSDLQQILS LLESNKDLLL TSSYLSDSGS TGEHTKSLVT 
421:	QYLNATGNRW CSWSLSQARL LTSFLPAQLL RLYQLMLFTL PGTPVFSYGD EIGLDAAALP 
481:	GQPMEAPVML WDESSFPDIP GAVSANMTVK GQSEDPGSLL SLFRRLSDQR SKERSLLHGD 
541:	FHAFSAGPGL FSYIRHWDQN ERFLVVLNFG DVGLSAGLQA SDLPASASLP AKADLLLSTQ 
601:	PGREEGSPLE LERLKLEPHE GLLLRFPYAA