Reactome | UniProt:P43005 SLC1A1

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UniProt:P43005 SLC1A1 Show undefined attributes

chain	chain:1-524
checksum	FC6244ADC9EA228F
comment	FUNCTION Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:21123949, PubMed:26690923, PubMed:33658209, PubMed:7521911, PubMed:7914198, PubMed:8857541). Can also transport L-cysteine (PubMed:21123949). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:26690923, PubMed:33658209, PubMed:7521911, PubMed:8857541). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:26690923, PubMed:8857541). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:21123949). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity). Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport (By similarity). Negatively regulated by ARL6IP5 (By similarity).CATALYTIC ACTIVITY K(+)(in) + L-glutamate(out) + 3 Na(+)(out) + H(+)(out) = K(+)(out) + L-glutamate(in) + 3 Na(+)(in) + H(+)(in)CATALYTIC ACTIVITY K(+)(in) + L-aspartate(out) + 3 Na(+)(out) + H(+)(out) = K(+)(out) + L-aspartate(in) + 3 Na(+)(in) + H(+)(in)CATALYTIC ACTIVITY D-aspartate(out) + K(+)(in) + 3 Na(+)(out) + H(+)(out) = D-aspartate(in) + K(+)(out) + 3 Na(+)(in) + H(+)(in)CATALYTIC ACTIVITY K(+)(in) + L-cysteine(out) + 3 Na(+)(out) + H(+)(out) = K(+)(out) + L-cysteine(in) + 3 Na(+)(in) + H(+)(in)BIOPHYSICOCHEMICAL PROPERTIES Homotrimer (PubMed:33658209). Interacts with ARL6IP5. Interacts with RTN2 (via N-terminus); the interaction promotes cell surface expression of SLC1A1. Interacts with SORCS2; this interaction is important for normal expression at the cell membrane (By similarity).INTERACTION Expressed in all tissues tested including liver, muscle, testis, ovary, retinoblastoma cell line, neurons and brain (in which there was dense expression in substantia nigra, red nucleus, hippocampus and in cerebral cortical layers).DOMAIN Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.PTM Glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. A deletion at the chromosome 9p24.2 locus, including SLC1A1, has been identified in patients with psychotic disorders (PubMed:21982423). This 84 kb deletion is immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence, extends through exon 1 of the SLC1A1 mRNA, co-segregates with disease in an extended 5-generation pedigree and increases disease risk more than 18-fold for family members (PubMed:23341099).SIMILARITY Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A1 subfamily.
created	[InstanceEdit:210485] 2008-01-14 10:59:03
crossReference	[DatabaseIdentifier:12219647] PDB:9D66 [DatabaseIdentifier:12817952] ZINC - World Drugs:EAA3_HUMAN [DatabaseIdentifier:12815217] ZINC target:P43005 [DatabaseIdentifier:12811872] ZINC - Substances:EAA3_HUMAN [DatabaseIdentifier:12809830] ZINC - Predictions - Purchasable:EAA3_HUMAN [DatabaseIdentifier:12807703] ZINC - Metabolites:EAA3_HUMAN [DatabaseIdentifier:12805408] ZINC - FDA approved:EAA3_HUMAN [DatabaseIdentifier:12804226] ZINC - Biogenic:EAA3_HUMAN [DatabaseIdentifier:12387601] RefSeq:NP_004161.4 [DatabaseIdentifier:12291689] Pharos - Targets:P43005 [DatabaseIdentifier:12274519] PRO:P43005 [DatabaseIdentifier:12219646] PDB:7NSG [DatabaseIdentifier:12219634] PDB:8CUD [DatabaseIdentifier:12219633] PDB:8CTC [DatabaseIdentifier:12219653] PDB:8CUJ [DatabaseIdentifier:12219640] PDB:9P4Z [DatabaseIdentifier:12219649] PDB:6X2Z [DatabaseIdentifier:12219654] PDB:8CV2 [DatabaseIdentifier:12219637] PDB:6S3Q [DatabaseIdentifier:12219639] PDB:8CUI [DatabaseIdentifier:12219641] PDB:9P4Y [DatabaseIdentifier:12219651] PDB:9D67 [DatabaseIdentifier:12219644] PDB:6X3E [DatabaseIdentifier:12219650] PDB:9D69 [DatabaseIdentifier:12219645] PDB:8CUA [DatabaseIdentifier:12219652] PDB:9D68 [DatabaseIdentifier:12219636] PDB:8CTD [DatabaseIdentifier:12219635] PDB:9P4X [DatabaseIdentifier:12219638] PDB:6X2L [DatabaseIdentifier:12219648] PDB:8CV3 [DatabaseIdentifier:12219643] PDB:9D6A [DatabaseIdentifier:11481343] ENSEMBL:ENSG00000106688 [DatabaseIdentifier:11582442] ENSEMBL:ENSP00000262352 [DatabaseIdentifier:11705141] ENSEMBL:ENST00000262352 [DatabaseIdentifier:11780269] Guide to Pharmacology - Targets:870 [DatabaseIdentifier:11793847] GeneCards:SLC1A1 [DatabaseIdentifier:11830711] HMDB Protein:HMDBP03094 [DatabaseIdentifier:11846836] HPA:ENSG00000106688-SLC1A1 [DatabaseIdentifier:12131498] OpenTargets:ENSG00000106688 [DatabaseIdentifier:12135850] Orphanet:SLC1A1 [DatabaseIdentifier:12219642] PDB:6X3F
databaseName	UniProt
dbId	210415
description	recommendedName: fullName evidence="16"Excitatory amino acid transporter 3 alternativeName: Excitatory amino-acid carrier 1 alternativeName: Neuronal and epithelial glutamate transporter alternativeName: Sodium-dependent glutamate/aspartate transporter 3 alternativeName: Solute carrier family 1 member 1
displayName	UniProt:P43005 SLC1A1
geneName	SLC1A1 EAAC1 EAAT3 HEAAC1
identifier	P43005
isSequenceChanged	false
keyword	3D-structure Amino-acid transport Cell membrane Chloride Disease variant Endosome Glycoprotein Membrane Metal-binding Phosphoprotein Potassium Proteomics identification Reference proteome Schizophrenia Sodium Symport Synapse Synaptosome Transmembrane Transmembrane helix Transport
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	SLC1A1
otherIdentifier	11721351_at 11721352_at 17083261 206396_PM_at 206396_at 213664_PM_at 213664_at 3160659 3160660 3160674 3160683 3160684 3160685 3160687 3160688 3160689 3160690 3160691 3160692 3160697 3160699 3160700 3160701 3160705 38267_at 38268_at 6505 8154135 A_14_P105964 A_23_P216468 A_24_P232252 GE58898 GO:0001662 GO:0001975 GO:0002027 GO:0003013 GO:0005253 GO:0005313 GO:0005314 GO:0005515 GO:0005576 GO:0005737 GO:0005768 GO:0005886 GO:0006575 GO:0006749 GO:0006750 GO:0006790 GO:0006801 GO:0006811 GO:0006836 GO:0006865 GO:0006882 GO:0006979 GO:0007212 GO:0007215 GO:0007268 GO:0007420 GO:0007611 GO:0007613 GO:0007625 GO:0007626 GO:0009410 GO:0009986 GO:0010460 GO:0010467 GO:0010842 GO:0015108 GO:0015179 GO:0015183 GO:0015293 GO:0015501 GO:0015813 GO:0016020 GO:0016324 GO:0019221 GO:0022008 GO:0030154 GO:0030424 GO:0030425 GO:0030534 GO:0031901 GO:0031902 GO:0031982 GO:0032279 GO:0033229 GO:0034330 GO:0034599 GO:0035633 GO:0036293 GO:0042417 GO:0042802 GO:0042883 GO:0043005 GO:0043025 GO:0043083 GO:0043197 GO:0043198 GO:0043204 GO:0043226 GO:0043278 GO:0043524 GO:0043679 GO:0045121 GO:0045184 GO:0045202 GO:0046872 GO:0048514 GO:0048678 GO:0048856 GO:0050808 GO:0050877 GO:0051402 GO:0051938 GO:0055037 GO:0055038 GO:0055085 GO:0060013 GO:0060041 GO:0060047 GO:0060291 GO:0061744 GO:0070062 GO:0070633 GO:0070777 GO:0070778 GO:0070779 GO:0071242 GO:0071288 GO:0071314 GO:0071577 GO:0071944 GO:0072347 GO:0090313 GO:0090461 GO:0097049 GO:0097386 GO:0097440 GO:0098657 GO:0098685 GO:0098712 GO:0098793 GO:0098877 GO:0099170 GO:0099544 GO:0140009 GO:0140010 GO:0150002 GO:0150104 GO:1902476 GO:1903712 GO:1903926 GO:1990635 GO:1990708 HMNXSV003000939 Hs.91139.1.A1_3p_at ILMN_1658917 PH_hs_0005070 TC09000029.hg U08989_at g4759121_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-210414] SLC1A1 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5625045] SLC1A1 R445W [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5625040] SLC1A1 84kb_del [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5625023] SLC1A1 I395del [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000106688] ENSEMBL:ENSG00000106688 SLC1A1 [ReferenceDNASequence:12693340] UCSC:P43005 SLC1A1 [ReferenceDNASequence:11346764] BioGPS Gene:6505 SLC1A1 [ReferenceDNASequence:11393182] COSMIC - genes:SLC1A1 SLC1A1 [ReferenceDNASequence:11422462] CTD Gene:6505 SLC1A1 [ReferenceDNASequence:11429119] dbSNP Gene:6505 SLC1A1 [ReferenceDNASequence:11825542] HGNC:10939 SLC1A1 [ReferenceDNASequence:11886868] KEGG:hsa:6505 SLC1A1 [ReferenceDNASequence:11976553] Monarch:6505 SLC1A1 [ReferenceDNASequence:12060646] NCBI Gene:6505 SLC1A1 [ReferenceDNASequence:12115954] OMIM:133550 SLC1A1
referenceTranscript	[ReferenceRNASequence:12569393] RefSeq:NM_004170.5 SLC1A1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	EAA3_HUMAN O75587 Q5VZ24 Q8N199 Q9UEW2
sequenceLength	524
species	[Species:48887] Homo sapiens
stId	uniprot:P43005
url	http://purl.uniprot.org/uniprot/P43005

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-210414] SLC1A1 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5625045] SLC1A1 R445W [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5625040] SLC1A1 84kb_del [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5625023] SLC1A1 I395del [plasma membrane]
(referenceSequence)	[ReplacedResidue:5624574] L-asparagine 445 replaced with L-tryptophan [FragmentDeletionModification:5624572] Deletion of residues 395 to 395
(interactor)	[UndirectedInteraction:11132997] UniProt:O60271 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11143739] UniProt:Q6UXV4 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11165713] UniProt:P09601 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11168365] UniProt:Q9BRQ6 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11174199] UniProt:P56937 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11196015] UniProt:O15120 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11197313] UniProt:P48960 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11207525] UniProt:Q8WUK0 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11209427] UniProt:P78382 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11234615] UniProt:P50416 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11234683] UniProt:Q9NPF0 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11238039] UniProt:Q7KZN9 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11240613] UniProt:O60493 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11248233] UniProt:P08240 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11275365] UniProt:O15357 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11290485] UniProt:P43007 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11293159] UniProt:Q12959 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11298725] UniProt:P49757 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11304135] UniProt:Q6IAN0 <-> UniProt:P43005 (IntAct) [UndirectedInteraction:11306411] UniProt:O43909 <-> UniProt:P43005 (IntAct)