| IED ID | IndEnz0001000067 |
| Enzyme Type ID | amylase000067 |
| Protein Name |
4F2 cell-surface antigen heavy chain 4F2hc 4F2 heavy chain antigen Lymphocyte activation antigen 4F2 large subunit Solute carrier family 3 member 2 CD antigen CD98 |
| Gene Name | SLC3A2 MDU1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPSASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTMSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGNLAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKKSIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFLAEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVTQYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALPGQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGDFHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQPGREEGSPLELERLKLEPHEGLLLRFPYAA |
| Enzyme Length | 630 |
| Uniprot Accession Number | P08195 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Component of several heterodimeric complexes involved in amino acid transport (PubMed:11557028, PubMed:9829974, PubMed:9751058, PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:30341327). The precise substrate specificity depends on the other subunit in the heterodimer (PubMed:9829974, PubMed:9751058, PubMed:10391915, PubMed:10574970, PubMed:30867591, PubMed:10903140). The complexes function as amino acid exchangers (PubMed:11557028, PubMed:10903140, PubMed:12117417, PubMed:12225859, PubMed:30867591). The homodimer 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 (PubMed:9751058, PubMed:11557028, PubMed:11311135, PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:25998567, PubMed:30867591). The heterodimer formed by SLC3A2 and SLC7A6 or SLC3A2 and SLC7A7 mediates the uptake of dibasic amino acids (PubMed:9829974, PubMed:10903140). The heterodimer with SLC7A5/LAT1 mediates the transport of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane (PubMed:11564694, PubMed:12225859). The heterodimer with SLC7A5/LAT1 is involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes (PubMed:12117417). The heterodimer with SLC7A5/LAT1 is involved in the uptake of leucine (PubMed:25998567, PubMed:30341327). When associated with LAPTM4B, the heterodimer with SLC7A5/LAT1 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). The heterodimer with SLC7A5/LAT1 may play a role in the transport of L-DOPA across the blood-brain barrier (By similarity). The heterodimer formed by SLC3A2 and SLC7A5/LAT1 or SLC3A2 and SLC7A8/LAT2 is involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane (PubMed:15769744). Together with ICAM1, regulates the transport activity of SLC7A8/LAT2 in polarized intestinal cells by generating and delivering intracellular signals (PubMed:12716892). Required for targeting of SLC7A5/LAT1 and SLC7A8/LAT2 to the plasma membrane and for channel activity (PubMed:9751058, PubMed:11311135, PubMed:30867591). Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine (PubMed:14603368). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier (By similarity). {ECO:0000250|UniProtKB:P10852, ECO:0000250|UniProtKB:Q794F9, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30341327, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Beta strand (23); Chain (1); Cross-link (2); Disulfide bond (1); Glycosylation (4); Helix (26); Initiator methionine (1); Modified residue (12); Mutagenesis (5); Region (1); Sequence conflict (12); Topological domain (2); Transmembrane (1); Turn (2) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Amino-acid transport;Cell junction;Cell membrane;Direct protein sequencing;Disulfide bond;Glycoprotein;Isopeptide bond;Lysosome;Membrane;Phosphoprotein;Reference proteome;Signal-anchor;Transmembrane;Transmembrane helix;Transport;Ubl conjugation |
| Interact With | O15354; Q01650; O52302; Q01650; Q9NX09; Q15125; P21333-2; P04792; O60333-2; Q5T3J3; P31153; Q9UPY5; Q9UHI5; O76024; Q96BH6 |
| Induction | INDUCTION: Expression is induced in resting peripheral blood T-lymphocytes following PHA stimulation. Expression increases at the time of maximal DNA synthesis, in fibroblasts stimulated to divide. Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore. Up-regulated in response to hydrogen peroxide (PubMed:30341327). {ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:30341327, ECO:0000269|PubMed:3265470, ECO:0000269|PubMed:3480538}.; INDUCTION: (Microbial infection) Up-regulated upon hepatitis C virus/HCV infection via NS3-A4 viral protein complex; the up-regulation is mediated by oxidative stress (PubMed:30341327). Up-regulation of the complex formed by SLC3A2 and SLC7A5/LAT1 upon hepatitis C virus/HCV infection (PubMed:30341327). {ECO:0000269|PubMed:30341327}. |
| Subcellular Location | SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:11742812}. Cell membrane {ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:16496379, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:3476959, ECO:0000269|PubMed:3480538, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974}; Single-pass type II membrane protein {ECO:0000269|PubMed:30867591}. Cell junction {ECO:0000250|UniProtKB:P10852}. Lysosome membrane {ECO:0000269|PubMed:25998567}. Melanosome {ECO:0000269|PubMed:17081065}. Note=Localized at the plasma membrane when associated with SLC7A5/LAT1 or SLC7A8/LAT2 (PubMed:9751058, PubMed:11311135). Localized to the apical membrane of placental syncytiotrophoblastic cells (PubMed:11742812). Recruited to lysosomes by LAPTM4B (PubMed:25998567). Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065). Located selectively at cell-cell adhesion sites (By similarity). Colocalized with SLC7A8/LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. Expressed in both luminal and abluminal membranes of brain capillary endothelial cells (By similarity). {ECO:0000250, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058}. |
| Modified Residue | MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:22814378"; MOD_RES 103; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 106; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:Q794F9"; MOD_RES 134; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 165; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"; MOD_RES 406; /note="Phosphoserine"; /evidence="ECO:0000305|PubMed:19065266"; MOD_RES 408; /note="Phosphoserine"; /evidence="ECO:0000305|PubMed:19065266"; MOD_RES 410; /note="Phosphoserine"; /evidence="ECO:0000305|PubMed:19065266"; MOD_RES 527; /note="Phosphoserine"; /evidence="ECO:0000305|PubMed:19065266"; MOD_RES 531; /note="Phosphoserine"; /evidence="ECO:0000305|PubMed:19065266"; MOD_RES P08195-2:2; /note="N-acetylserine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895"; MOD_RES P08195-2:2; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21406692" |
| Post Translational Modification | PTM: Phosphorylation on Ser-406; Ser-408 or Ser-410 and on Ser-527 or Ser-531 by ecto-protein kinases favors heterotypic cell-cell interactions. {ECO:0000269|PubMed:19065266}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (6); X-ray crystallography (3) |
| Cross Reference PDB | 2DH2; 2DH3; 6IRS; 6IRT; 6JMQ; 6JMR; 6S8V; 7B00; 7CCS; |
| Mapped Pubmed ID | 10049700; 10080182; 10080183; 10631139; 10863037; 11417227; 15151999; 15657067; 15776427; 15901826; 15918515; 16799092; 17353931; 19738201; 19805454; 20217867; 21252943; 21397861; 21656680; 21911578; 22304920; 22593156; 23289620; 23606334; 23902751; 24189400; 25609649; 26514267; 26638075; 26752685; 31160781; 32089738; 33016372; |
| Motif | |
| Gene Encoded By | |
| Mass | 67,994 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=295 uM for glutamine (in the presence of NaCl) {ECO:0000269|PubMed:10903140}; KM=236 uM for leucine (in the presence of NaCl) {ECO:0000269|PubMed:10903140}; KM=120 uM for arginine (in the presence of NaCl) {ECO:0000269|PubMed:10903140}; KM=138 uM for arginine (in the absence of NaCl) {ECO:0000269|PubMed:10903140}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |