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2.A.3.8.25
Large neutral amino acids transporter small subunit 1 (4F2 light chain) (4F2 LC) (4F2LC) (CD98 light chain; SLC3A2) (Integral membrane protein E16) (L-type amino acid transporter 1) (hLAT1) (Solute carrier family 7 member 5) (y+ system cationic and neutral amino acid transporter).  The heavy chain, CD98hc, modulates integrin signaling, plays a role in cell-to-cell fusion, and is essential for Brucella infection (Keriel et al. 2015).  In addition to several large neutral L-amino acids, Lat1 in conjunction with 4F2hc, transports S-nitroso-L-cysteine (Li and Whorton 2007), is important for transport of certain drugs into the brain, and is important for cancer (Lee et al. 2019). LAT1/CD98 mediates a Na+ and pH-independent antiport of amino acids (Scalise et al. 2018). It has been demonstrated that the preferred substrate is histidine and that CD98 is not required for transport, being plausibly involved in routing LAT1 to the plasma membrane. Homology models have been built on the basis of the AdiC transporter from E.coli. Crucial residues for substrate recognition and gating have been identified using a combined approach of bioinformatics and site-directed mutagenesis coupled to functional assays. LAT1 is involved in important human diseases such as neurological disorders and cancer (Scalise et al. 2018). The cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3-A resolution has been determined (Lee et al. 2019). LAT1 features a canonical Leu T-fold and exhibits an unusual loop structure on transmembrane helix 6, creating an extended cavity that might accommodate bulky amino acids and drugs. CD98hc engages with LAT1 through extracellular, transmembrane and putative cholesterol-mediated interactions.

Accession Number:Q01650
Protein Name:Large neutral amino acids transporter small subunit 1
Length:507
Molecular Weight:55010.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cytoplasm1
Substrate Amino acids, S-nitroso-L-cysteine

Cross database links:

Genevestigator: Q01650
HEGENOM: HOG000098892
Entrez Gene ID: 8140   
KEGG: hsa:8140   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0005829 C:cytosol
GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015179 F:L-amino acid transmembrane transporter activity
GO:0015175 F:neutral amino acid transmembrane transporter activity
GO:0042605 F:peptide antigen binding
GO:0007596 P:blood coagulation
GO:0030154 P:cell differentiation
GO:0006520 P:cellular amino acid metabolic process
GO:0006811 P:ion transport
GO:0050900 P:leukocyte migration
GO:0007399 P:nervous system development

References (24)

[1] “Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.”  Mastroberardino L.et.al.   9751058
[2] “Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function.”  Prasad P.D.et.al.   10049700
[3] “Primary structure of the light chain of fusion regulatory protein-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16.”  Tsurudome M.et.al.   10072483
[4] “Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.”  Yanagida O.et.al.   11557028
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “A novel transiently expressed, integral membrane protein linked to cell activation. Molecular cloning via the rapid degradation signal AUUUA.”  Gaugitsch H.W.et.al.   1597461
[7] “Identification of a membrane protein, LAT-2, that co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.”  Pineda M.et.al.   10391915
[8] “LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.”  Rossier G.et.al.   10574970
[9] “Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains.”  Broeer A.et.al.   11311135
[10] “Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta.”  Ritchie J.W.A.et.al.   11389679
[11] “Thyroid hormone transport by the heterodimeric human system L amino acid transporter.”  Friesema E.C.H.et.al.   11564694
[12] “Expression and regulation of 4F2hc and hLAT1 in human trophoblasts.”  Okamoto Y.et.al.   11742812
[13] “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
[14] “Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells.”  Kim D.K.et.al.   12225859
[15] “Identification and functional characterization of a Na+-independent large neutral amino acid transporter, LAT1, in human and rabbit cornea.”  Jain-Vakkalagadda B.et.al.   12824232
[16] “Large-scale characterization of HeLa cell nuclear phosphoproteins.”  Beausoleil S.A.et.al.   15302935
[17] “Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells.”  Fraga S.et.al.   16027961
[18] “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
[19] “Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC.”  Gevaert K.et.al.   16097034
[20] “L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors.”  Nawashiro H.et.al.   16496379
[21] “Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry.”  Meierhofer D.et.al.   18781797
[22] “Functional characterization of tyrosine transport in fibroblast cells from healthy controls.”  Vumma R.et.al.   18262359
[23] “Large-scale proteomics analysis of the human kinome.”  Oppermann F.S.et.al.   19369195
[24] “Initial characterization of the human central proteome.”  Burkard T.R.et.al.   21269460

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FASTA formatted sequence
1:	MAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSAPAGE GEGVTLQRNI TLLNGVAIIV 
61:	GTIIGSGIFV TPTGVLKEAG SPGLALVVWA ACGVFSIVGA LCYAELGTTI SKSGGDYAYM 
121:	LEVYGSLPAF LKLWIELLII RPSSQYIVAL VFATYLLKPL FPTCPVPEEA AKLVACLCVL 
181:	LLTAVNCYSV KAATRVQDAF AAAKLLALAL IILLGFVQIG KGDVSNLDPN FSFEGTKLDV 
241:	GNIVLALYSG LFAYGGWNYL NFVTEEMINP YRNLPLAIII SLPIVTLVYV LTNLAYFTTL 
301:	STEQMLSSEA VAVDFGNYHL GVMSWIIPVF VGLSCFGSVN GSLFTSSRLF FVGSREGHLP 
361:	SILSMIHPQL LTPVPSLVFT CVMTLLYAFS KDIFSVINFF SFFNWLCVAL AIIGMIWLRH 
421:	RKPELERPIK VNLALPVFFI LACLFLIAVS FWKTPVECGI GFTIILSGLP VYFFGVWWKN 
481:	KPKWLLQGIF STTVLCQKLM QVVPQET