Details of Protein

General Information of Protein (ID: PRT01334)
Name Lymphocyte activation antigen 4F2 (SLC3A2)
Synonyms   Click to Show/Hide Synonyms of This Protein
4F2hc; 4F2 heavy chain antigen; Lymphocyte activation antigen 4F2 large subunit; Solute carrier family 3 member 2; CD antigen CD98; SLC3A2; MDU1
Gene Name SLC3A2 Gene ID
6520
UniProt ID
P08195
Family Amino acid/polyamine transporter (AAPT)
TC Number   TC: 2.A.3.8.18  (Click to Show/Hide the Complete TC Tree)
Amino acid/polyamine transporter (AAPT)
The L-type Amino Acid Transporter (LAT) Family
TC: 2.A.3.8.18
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPS
ASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTMSQDTEVDMKEVELNELEP
EKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVR
TRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGN
LAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKK
SIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFL
AEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVT
QYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALP
GQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGD
FHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQ
PGREEGSPLELERLKLEPHEGLLLRFPYAA
Structure
2DH2 ; 2DH3 ; 6IRS ; 6IRT ; 6JMQ ; 6JMR ; 6S8V ; 7CCS
Function Component of several heterodimeric amino acid transporter complexes. The precise substrate specificity depends on the other subunit in the heterodimer. The heterodimer with SLC3A2 functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, L-DOPA, leucine, histidine, methionine and tryptophan. The complexes with SLC7A6 and SLC7A7 mediate uptake of dibasic amino acids. The complexes function as amino acid exchangers. Required for targeting of SLC7A5 and SLC7A8 to the plasma membrane and for channel activity. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. The heterodimer with SLC7A5/LAT1 may play a role in the transport of L-DOPA across the blood-brain barrier. May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier. The heterodimer with SLC7A5/LAT1 can mediate the transport of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane. When associated with SLC7A5 or SLC7A8, involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. The heterodimer with SLC7A5 is involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes. Together with ICAM1, regulates the transport activity SLC7A8 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Organic acids and derivatives
            Arginine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC3A2
                      Induced Change Arginine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC3A2 and SLC7A8 leads to the increase of arginine levels compared with control group.
            Glutamine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC3A2
                      Induced Change Glutamine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC3A2 and SLC7A8 leads to the increase of glutamine levels compared with control group.
            Isoleucine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC3A2
                      Induced Change Isoleucine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC3A2 and SLC7A8 leads to the increase of isoleucine levels compared with control group.
            Leucine Click to Show/Hide the Full List of Regulating Pair(s):   7 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1], [2]
                      Introduced Variation Overexpression of SLC3A2
                      Induced Change Leucine concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC3A2 and SLC7A8 leads to the increase of leucine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Mutation (extracellular domain residues 235-631) of SLC3A2
                      Induced Change Leucine concentration: decrease (FC = 0.10)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (extracellular domain residues 235-631) of SLC3A2 leads to the decrease of leucine levels compared with control group.
               Regulating Pair (3) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Mutation (K533E) of SLC3A2
                      Induced Change Leucine concentration: decrease (FC = 0.65)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (K533E) of SLC3A2 leads to the decrease of leucine levels compared with control group.
               Regulating Pair (4) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Mutation (R183A) of SLC3A2
                      Induced Change Leucine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (R183A) of SLC3A2 leads to the decrease of leucine levels compared with control group.
               Regulating Pair (5) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Mutation (R183E) of SLC3A2
                      Induced Change Leucine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (R183E) of SLC3A2 leads to the decrease of leucine levels compared with control group.
               Regulating Pair (6) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Mutation (R183K) of SLC3A2
                      Induced Change Leucine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (R183K) of SLC3A2 leads to the decrease of leucine levels compared with control group.
               Regulating Pair (7) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Mutation (R183L) of SLC3A2
                      Induced Change Leucine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that mutation (R183L) of SLC3A2 leads to the decrease of leucine levels compared with control group.
References
1 The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine. Biochem J. 2000 Aug 1;349 Pt 3(Pt 3):787-95.
2 Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001 Oct 1;1514(2):291-302.
3 Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex. Nature. 2019 Apr;568(7750):127-130.

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