SLC3A2
entrez
6520
canonical
uniprot
P08195
canonical
ensembl
ENSG00000168003
resolver
ensp
ENSP00000340815
resolver
ensp
ENSP00000367121
resolver
ensp
ENSP00000367122
resolver
ensp
ENSP00000367123
resolver
genesymbol
SLC3A2
resolver
genesymbol_syn
MDU1
resolver
hgnc
HGNC:11026
resolver
uniprot
J3KPF3
resolver
uniprot
Q13543
resolver
uniprot_entry
4F2_HUMAN
resolver
uniprot_sec
J3KPF3
resolver
uniprot_sec
Q13543
resolver
amino_acid_sequence
MSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGNLAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKKSIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFLAEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVTQYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALPGQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGDFHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQPGREEGSPLELERLKLEPHEGLLLRFPYAA
uniprot
proteins
function
FUNCTION: Acts as a chaperone that facilitates biogenesis and trafficking of functional transporter heterodimers to the plasma membrane. Forms heterodimers with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049, PubMed:37918808). Heterodimers function as amino acid exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocate neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for the plasma membrane localization, stability, and transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406, PubMed:37918808). When associated with LAPTM4B, the SLC3A2/SLC7A5 heterodimer is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, 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:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:37918808, 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}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}.
uniprot
proteins
mass_dalton
57945
uniprot
proteins
mutagenesis
MUTAGEN 81; /note="R->A,E,K,L: Strongly decreased leucine transport activity."; /evidence="ECO:0000269|PubMed:30867591"; MUTAGEN 109; /note="C->S: Abolishes dimerization, leucine uptake and interaction with beta-1 integrins."; /evidence="ECO:0000269|PubMed:11696247, ECO:0000269|PubMed:17724034, ECO:0000269|PubMed:9829974"; MUTAGEN 133..529; /note="Missing: Nearly abolishes leucine transport activity."; /evidence="ECO:0000269|PubMed:30867591"; MUTAGEN 172; /note="A->N: Increases glycosylation; when associated with N-254 and N-391."; /evidence="ECO:0000269|PubMed:37918808"; MUTAGEN 254; /note="D->N: Increases glycosylation; when associated with N-172 and N-391."; /evidence="ECO:0000269|PubMed:37918808"; MUTAGEN 264; /note="N->D: Moderately increases protein endocytosis."; /evidence="ECO:0000269|PubMed:37918808"; MUTAGEN 264; /note="N->Q: Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-280; Q-323 and Q-405."; /evidence="ECO:0000269|PubMed:36028562"; MUTAGEN 280; /note="N->D: Strongly increases protein endocytosis."; /evidence="ECO:0000269|PubMed:37918808"; MUTAGEN 280; /note="N->Q: Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-264; Q-323 and Q-405."; /evidence="ECO:0000269|PubMed:36028562"; MUTAGEN 323; /note="N->Q: Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-264 Q-280 and Q-405."; /evidence="ECO:0000269|PubMed:36028562"; MUTAGEN 330; /note="C->S: No effect on dimerization, leucine uptake or interaction with beta-1 integrins."; /evidence="ECO:0000269|PubMed:11696247, ECO:0000269|PubMed:9829974"; MUTAGEN 391; /note="D->N: Increases glycosylation; when associated with N-172 and N-254."; /evidence="ECO:0000269|PubMed:37918808"; MUTAGEN 405; /note="N->Q: Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-264 Q-280 and Q-323."; /evidence="ECO:0000269|PubMed:36028562"; MUTAGEN 431; /note="K->E: Strongly decreased leucine transport activity."; /evidence="ECO:0000269|PubMed:30867591
uniprot
proteins
post_translational_modification
PTM: N-glycosylated; N-glycosylation is crucial for SLC3A2 stability and trafficking to the plasma membrane (PubMed:36028562). SLC3A2 surface retention and endocytosis are precisely balanced by N-glycosylation (PubMed:37918808). N-glycosylation at Asn-280 stabilizes SLC3A2 in the galectin-3 lattice against coated-pit endocytosis (PubMed:37918808). N-glycosylation at Asn-264 promotes glycolipid-galectin-3-driven endocytosis (PubMed:37918808). N-glycosylation promotes interaction with proteins such as SLC7A5 and SLC7A11 (PubMed:37918808). When N-glycosylation is reduced, this promotes the recruitment of CD44 along with transporters required in the response to stress (PubMed:37918808). {ECO:0000269|PubMed:36028562, ECO:0000269|PubMed:37918808}.; PTM: Phosphorylation on Ser-305; Ser-307 or Ser-309 and on Ser-426 or Ser-430 by ecto-protein kinases favors heterotypic cell-cell interactions. {ECO:0000269|PubMed:19065266}.
uniprot
proteins
protein_family
SLC3A transporter family
uniprot
proteins
pubmed
10391915
uniprot
proteins
pubmed
10574970
uniprot
proteins
pubmed
10903140
uniprot
proteins
pubmed
11121428
uniprot
proteins
pubmed
11311135
uniprot
proteins
pubmed
11389679
uniprot
proteins
pubmed
11557028
uniprot
proteins
pubmed
11564694
uniprot
proteins
pubmed
11696247
uniprot
proteins
pubmed
11742812
uniprot
proteins
pubmed
11840567
uniprot
proteins
pubmed
12117417
uniprot
proteins
pubmed
12225859
uniprot
proteins
pubmed
12270127
uniprot
proteins
pubmed
12716892
uniprot
proteins
pubmed
12754519
uniprot
proteins
pubmed
14603368
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15625115
uniprot
proteins
pubmed
15769744
uniprot
proteins
pubmed
15980244
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16496379
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
17081065
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17724034
uniprot
proteins
pubmed
19065266
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19292886
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23116296
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
25998567
uniprot
proteins
pubmed
28350098
uniprot
proteins
pubmed
30341327
uniprot
proteins
pubmed
3036867
uniprot
proteins
pubmed
30867591
uniprot
proteins
pubmed
3265470
uniprot
proteins
pubmed
33066406
uniprot
proteins
pubmed
33298890
uniprot
proteins
pubmed
33758168
uniprot
proteins
pubmed
34294905
uniprot
proteins
pubmed
3476959
uniprot
proteins
pubmed
3480538
uniprot
proteins
pubmed
34880232
uniprot
proteins
pubmed
35352032
uniprot
proteins
pubmed
36028562
uniprot
proteins
pubmed
37918808
uniprot
proteins
pubmed
40280132
uniprot
proteins
pubmed
9751058
uniprot
proteins
pubmed
9829974
uniprot
proteins
pubmed
9878049
uniprot
proteins
sequence_length
529
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:11742812}. Cell membrane {ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, 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:36028562, ECO:0000269|PubMed:37918808, 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, ECO:0000269|PubMed:40280132}. Melanosome {ECO:0000269|PubMed:17081065}. Basolateral cell membrane {ECO:0000250|UniProtKB:P10852}. Note=Localized at the plasma membrane when associated with SLC7A5/LAT1 or SLC7A8/LAT2 (PubMed:11311135, PubMed:9751058). 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|UniProtKB:P10852, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058}.
uniprot
proteins
transmembrane_region
TRANSMEM 84..104; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000269|PubMed:30867591
uniprot
proteins