Reactome | UniProt:Q8NDX2 SLC17A8

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UniProt:Q8NDX2 SLC17A8 Show undefined attributes

chain	chain:1-589
checksum	E74DDC91495F8775
comment	FUNCTION Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, sodium and phosphate (PubMed:12151341, PubMed:33440152). At the synaptic vesicle membrane, mainly functions as an uniporter that mediates the uptake of L-glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells (PubMed:12151341). The L-glutamate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (PubMed:12151341). In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification (By similarity). At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation (Probable). The symporter activity is electrogenic (PubMed:33440152). Moreover, operates synergistically with SLC18A3/VACHT under a constant H(+) gradient, thereby allowing striatal vesicular acetylcholine uptake (By similarity).CATALYTIC ACTIVITY L-glutamate(out) = L-glutamate(in)CATALYTIC ACTIVITY 3 Na(+)(out) + phosphate(out) = 3 Na(+)(in) + phosphate(in)CATALYTIC ACTIVITY chloride(in) = chloride(out)ACTIVITY REGULATION The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release.INTERACTION Expressed in amygdala, cerebellum, hippocampus, medulla, spinal cord and thalamus.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.
created	[InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12
crossReference	[DatabaseIdentifier:12360798] RefSeq:NP_001138760.1 [DatabaseIdentifier:12360799] RefSeq:NP_647480.1 [DatabaseIdentifier:12283975] Pharos - Targets:Q8NDX2 [DatabaseIdentifier:12262319] PRO:Q8NDX2 [DatabaseIdentifier:12134815] Orphanet:SLC17A8 [DatabaseIdentifier:12123655] OpenTargets:ENSG00000179520 [DatabaseIdentifier:11839142] HPA:ENSG00000179520-SLC17A8 [DatabaseIdentifier:11828932] HMDB Protein:HMDBP03945 [DatabaseIdentifier:11801584] GlyGen:Q8NDX2 [DatabaseIdentifier:11786058] GeneCards:SLC17A8 [DatabaseIdentifier:11778646] Guide to Pharmacology - Targets:1009 [DatabaseIdentifier:11688475] ENSEMBL:ENST00000323346 [DatabaseIdentifier:11688474] ENSEMBL:ENST00000392989 [DatabaseIdentifier:11565775] ENSEMBL:ENSP00000316909 [DatabaseIdentifier:11565776] ENSEMBL:ENSP00000376715 [DatabaseIdentifier:11469426] ENSEMBL:ENSG00000179520
databaseName	UniProt
dbId	357185
description	recommendedName: fullName evidence="6"Vesicular glutamate transporter 3 shortName evidence="6"VGluT3 alternativeName: Solute carrier family 17 member 8
displayName	UniProt:Q8NDX2 SLC17A8
geneName	SLC17A8 VGLUT3
identifier	Q8NDX2
isSequenceChanged	false
keyword	Alternative splicing Cell membrane Chloride Chloride channel Cytoplasmic vesicle Deafness Disease variant Glycoprotein Hearing Ion channel Ion transport Membrane Neurotransmitter transport Non-syndromic deafness Phosphate transport Proteomics identification Reference proteome Sodium Sodium transport Symport Synapse Synaptosome Transmembrane Transmembrane helix Transport
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	SLC17A8
otherIdentifier	11734456_a_at 11738625_a_at 1553415_PM_at 1553415_at 16755652 246213 3428191 3428192 3428195 3428196 3428197 3428198 3428200 3428202 3428204 3428205 3428206 3428207 3428208 3428209 3428210 3428211 3428212 3428213 3428214 7957819 A_14_P106429 A_14_P125231 A_23_P159076 A_24_P124647 GE533132 GO:0003407 GO:0005254 GO:0005313 GO:0005326 GO:0005436 GO:0005515 GO:0005768 GO:0005771 GO:0005886 GO:0006811 GO:0006814 GO:0006817 GO:0006821 GO:0006836 GO:0007605 GO:0008021 GO:0015291 GO:0015293 GO:0015813 GO:0016020 GO:0022857 GO:0030425 GO:0030672 GO:0031410 GO:0034220 GO:0034707 GO:0035249 GO:0035725 GO:0043005 GO:0043025 GO:0043204 GO:0043679 GO:0044341 GO:0045202 GO:0048856 GO:0050803 GO:0050877 GO:0051631 GO:0051938 GO:0051951 GO:0055062 GO:0055085 GO:0060076 GO:0090102 GO:0097440 GO:0097441 GO:0097451 GO:0098700 GO:0098978 GO:0140788 GO:1902476 GO:1990030 HMNXSV003025855 Hs2.116871.1.S1_3p_at Hs2.116871.1.S1_3p_s_at Hs2.116871.1.S1_3p_x_at ILMN_1767842 PH_hs_0006406 TC12000776.hg
physicalEntity	[EntityWithAccessionedSequence:R-HSA-9659621] SLC17A8 [clathrin-sculpted glutamate transport vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5624277] SLC17A8 A211V [synaptic vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-428558] SLC17A8 [synaptic vesicle membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12736690] UCSC:Q8NDX2 SLC17A8 [ReferenceDNASequence:12109154] OMIM:607557 SLC17A8 [ReferenceDNASequence:12048276] NCBI Gene:246213 SLC17A8 [ReferenceDNASequence:11964183] Monarch:246213 SLC17A8 [ReferenceDNASequence:11875724] KEGG:hsa:246213 SLC17A8 [ReferenceDNASequence:11817689] HGNC:20151 SLC17A8 [ReferenceDNASequence:11436006] dbSNP Gene:246213 SLC17A8 [ReferenceDNASequence:11410897] CTD Gene:246213 SLC17A8 [ReferenceDNASequence:11399082] COSMIC - genes:SLC17A8 SLC17A8 [ReferenceDNASequence:11334394] BioGPS Gene:246213 SLC17A8 [ReferenceDNASequence:ensembl:ENSG00000179520] ENSEMBL:ENSG00000179520 SLC17A8
referenceTranscript	[ReferenceRNASequence:12542632] RefSeq:NM_001145288.2 SLC17A8 [ReferenceRNASequence:12542631] RefSeq:NM_139319.3 SLC17A8
schemaClass	ReferenceGeneProduct
secondaryIdentifier	VGLU3_HUMAN B3KXZ6 B7ZKV4 Q17RQ8
sequenceLength	589
species	[Species:48887] Homo sapiens
stId	uniprot:Q8NDX2
url	http://purl.uniprot.org/uniprot/Q8NDX2

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-9659621] SLC17A8 [clathrin-sculpted glutamate transport vesicle membrane] [EntityWithAccessionedSequence:R-HSA-5624277] SLC17A8 A211V [synaptic vesicle membrane] [EntityWithAccessionedSequence:R-HSA-428558] SLC17A8 [synaptic vesicle membrane]
(referenceSequence)	[ReplacedResidue:5624279] L-alanine 211 replaced with L-valine