VGLU3_MOUSE
ID VGLU3_MOUSE Reviewed; 601 AA.
AC Q8BFU8;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Vesicular glutamate transporter 3 {ECO:0000303|PubMed:12384506};
DE Short=VGluT3 {ECO:0000303|PubMed:12384506};
DE AltName: Full=Solute carrier family 17 member 8;
GN Name=Slc17a8 {ECO:0000312|MGI:MGI:3039629}; Synonyms=Vglut3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=12384506; DOI=10.1074/jbc.m206738200;
RA Schaefer M.K.-H., Varoqui H., Defamie N., Weihe E., Erickson J.D.;
RT "Molecular cloning and functional identification of mouse vesicular
RT glutamate transporter 3 and its expression in subsets of novel excitatory
RT neurons.";
RL J. Biol. Chem. 277:50734-50748(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=18674745; DOI=10.1016/j.ajhg.2008.07.008;
RA Ruel J., Emery S., Nouvian R., Bersot T., Amilhon B., Van Rybroek J.M.,
RA Rebillard G., Lenoir M., Eybalin M., Delprat B., Sivakumaran T.A.,
RA Giros B., El Mestikawy S., Moser T., Smith R.J.H., Lesperance M.M.,
RA Puel J.-L.;
RT "Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3,
RT underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in
RT null mice.";
RL Am. J. Hum. Genet. 83:278-292(2008).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18278042; DOI=10.1038/nn2052;
RA Gras C., Amilhon B., Lepicard E.M., Poirel O., Vinatier J., Herbin M.,
RA Dumas S., Tzavara E.T., Wade M.R., Nomikos G.G., Hanoun N., Saurini F.,
RA Kemel M.-L., Gasnier B., Giros B., Mestikawy S.E.;
RT "The vesicular glutamate transporter VGLUT3 synergizes striatal
RT acetylcholine tone.";
RL Nat. Neurosci. 11:292-300(2008).
RN [5]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=18080752; DOI=10.1007/s11064-007-9546-z;
RA Mackenzie B., Illing A.C., Morris M.E.K., Varoqui H., Erickson J.D.;
RT "Analysis of a vesicular glutamate transporter (VGLUT2) supports a cell-
RT leakage mode in addition to vesicular packaging.";
RL Neurochem. Res. 33:238-247(2008).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18215623; DOI=10.1016/j.neuron.2007.11.032;
RA Seal R.P., Akil O., Yi E., Weber C.M., Grant L., Yoo J., Clause A.,
RA Kandler K., Noebels J.L., Glowatzki E., Lustig L.R., Edwards R.H.;
RT "Sensorineural deafness and seizures in mice lacking vesicular glutamate
RT transporter 3.";
RL Neuron 57:263-275(2008).
CC -!- FUNCTION: Multifunctional transporter that transports L-glutamate as
CC well as multiple ions such as chloride, sodium and phosphate
CC (PubMed:18215623, PubMed:18080752, PubMed:12384506). At the synaptic
CC vesicle membrane, mainly functions as an uniporter that mediates the
CC uptake of L-glutamate into synaptic vesicles at presynaptic nerve
CC terminals of excitatory neural cells (PubMed:18215623, PubMed:18080752,
CC PubMed:12384506). The L-glutamate uniporter activity is electrogenic
CC and is driven by the proton electrochemical gradient, mainly by the
CC electrical gradient established by the vacuolar H(+)-ATPase across the
CC synaptic vesicle membrane (PubMed:12384506). In addition, functions as
CC a chloride channel that allows a chloride permeation through the
CC synaptic vesicle membrane that affects the proton electrochemical
CC gradient and promotes synaptic vesicles acidification (By similarity).
CC At the plasma membrane, following exocytosis, functions as a symporter
CC of Na(+) and phosphate from the extracellular space to the cytoplasm
CC allowing synaptic phosphate homeostasis regulation (By similarity). The
CC symporter activity is electrogenic (By similarity). Moreover, operates
CC synergistically with SLC18A3/VACHT under a constant H(+) gradient,
CC thereby allowing striatal vesicular acetylcholine uptake
CC (PubMed:18278042). {ECO:0000250|UniProtKB:Q7TSF2,
CC ECO:0000250|UniProtKB:Q8NDX2, ECO:0000269|PubMed:12384506,
CC ECO:0000269|PubMed:18080752, ECO:0000269|PubMed:18215623,
CC ECO:0000269|PubMed:18278042}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(out) = L-glutamate(in); Xref=Rhea:RHEA:66336,
CC ChEBI:CHEBI:29985; Evidence={ECO:0000269|PubMed:12384506,
CC ECO:0000269|PubMed:18080752};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 Na(+)(out) + phosphate(out) = 3 Na(+)(in) + phosphate(in);
CC Xref=Rhea:RHEA:71255, ChEBI:CHEBI:29101, ChEBI:CHEBI:43474;
CC Evidence={ECO:0000250|UniProtKB:Q8NDX2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q7TSF2};
CC -!- ACTIVITY REGULATION: The L-glutamate uniporter activity exhibits a
CC biphasic dependence on chloride concentration. Chloride channel
CC activity is allosterically activated by lumenal H(+) and Cl(-) leading
CC to synaptic vesicles acidification. The L-glutamate transport activity
CC is allosterically activated by lumenal H(+) and Cl(-), preventing non-
CC vesicular L-glutamate release. {ECO:0000250|UniProtKB:Q7TSF2}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.3 mM for L-glutamate {ECO:0000269|PubMed:12384506};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:Q7TSF2}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8NDX2}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8NDX2}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q7TSF2}.
CC -!- TISSUE SPECIFICITY: Expressed in restricted areas of the brain. Highest
CC expression is found in the neurons of the basal forebrain, the
CC hippocampal formation, and the majority of the neurons of the
CC mesencephalic raphe nuclei. Expressed in inner hair cells of the ear.
CC {ECO:0000269|PubMed:12384506, ECO:0000269|PubMed:18215623}.
CC -!- DEVELOPMENTAL STAGE: Expression peaks at P7 in the brain. Expressed in
CC inner hair cells from 19 dpc onwards. {ECO:0000269|PubMed:12384506,
CC ECO:0000269|PubMed:18215623}.
CC -!- DISRUPTION PHENOTYPE: Mice are hyperactive and suffer from
CC intermittent, spontaneous cortical seizures. They exhibit reduced
CC cholinergic transmission in the ventral portion of the striatum and
CC defective acetylcholine release. They are hypersensitive to cocaine and
CC less prone to haloperidol-induced catalepsy.
CC {ECO:0000269|PubMed:18215623, ECO:0000269|PubMed:18278042,
CC ECO:0000269|PubMed:18674745}.
CC -!- MISCELLANEOUS: Mice defective in Slc17a8 are profoundly deaf owing to
CC the absence of glutamate release from hair cells at the first synapse
CC in the auditory pathway. They lack auditory-nerve responses to acoustic
CC stimuli, although auditory brainstem responses could be elicited by
CC electrical stimuli.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sodium/anion
CC cotransporter family. VGLUT subfamily. {ECO:0000305}.
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DR EMBL; AF510321; AAN74643.1; -; mRNA.
DR EMBL; BC042593; AAH42593.1; -; mRNA.
DR CCDS; CCDS24117.1; -.
DR RefSeq; NP_892004.1; NM_182959.3.
DR AlphaFoldDB; Q8BFU8; -.
DR SMR; Q8BFU8; -.
DR STRING; 10090.ENSMUSP00000020102; -.
DR TCDB; 2.A.1.14.23; the major facilitator superfamily (mfs).
DR GlyGen; Q8BFU8; 1 site.
DR SwissPalm; Q8BFU8; -.
DR PaxDb; Q8BFU8; -.
DR PRIDE; Q8BFU8; -.
DR ProteomicsDB; 300167; -.
DR ABCD; Q8BFU8; 1 sequenced antibody.
DR Antibodypedia; 57947; 85 antibodies from 13 providers.
DR DNASU; 216227; -.
DR Ensembl; ENSMUST00000020102; ENSMUSP00000020102; ENSMUSG00000019935.
DR GeneID; 216227; -.
DR KEGG; mmu:216227; -.
DR UCSC; uc007gsj.1; mouse.
DR CTD; 246213; -.
DR MGI; MGI:3039629; Slc17a8.
DR VEuPathDB; HostDB:ENSMUSG00000019935; -.
DR eggNOG; KOG2532; Eukaryota.
DR GeneTree; ENSGT00940000158187; -.
DR InParanoid; Q8BFU8; -.
DR OMA; RRTTWGM; -.
DR OrthoDB; 497052at2759; -.
DR PhylomeDB; Q8BFU8; -.
DR TreeFam; TF313535; -.
DR Reactome; R-MMU-428643; Organic anion transporters.
DR BioGRID-ORCS; 216227; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q8BFU8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BFU8; protein.
DR Bgee; ENSMUSG00000019935; Expressed in spiral organ of cochlea and 42 other tissues.
DR ExpressionAtlas; Q8BFU8; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0097440; C:apical dendrite; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0097441; C:basal dendrite; ISO:MGI.
DR GO; GO:0060203; C:clathrin-sculpted glutamate transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0060076; C:excitatory synapse; ISO:MGI.
DR GO; GO:0097451; C:glial limiting end-foot; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0005771; C:multivesicular body; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:1990030; C:pericellular basket; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IDA:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:MGI.
DR GO; GO:0005254; F:chloride channel activity; ISS:UniProtKB.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005436; F:sodium:phosphate symporter activity; ISS:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0006820; P:anion transport; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0051938; P:L-glutamate import; ISS:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:UniProtKB.
DR GO; GO:0003407; P:neural retina development; IEA:Ensembl.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; ISO:MGI.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISS:UniProtKB.
DR GO; GO:0051951; P:positive regulation of glutamate uptake involved in transmission of nerve impulse; IMP:UniProtKB.
DR GO; GO:0051631; P:regulation of acetylcholine uptake; IMP:UniProtKB.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR GO; GO:0044341; P:sodium-dependent phosphate transport; ISS:UniProtKB.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Chloride; Chloride channel; Cytoplasmic vesicle; Deafness;
KW Glycoprotein; Hearing; Ion channel; Ion transport; Membrane;
KW Neurotransmitter transport; Phosphate transport; Reference proteome;
KW Sodium; Sodium transport; Symport; Synapse; Synaptosome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..601
FT /note="Vesicular glutamate transporter 3"
FT /id="PRO_0000331615"
FT TOPO_DOM 1..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..143
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..195
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..234
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..255
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 256..262
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..366
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..387
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 388..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..426
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 427..447
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 448..460
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..481
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 482..494
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..598
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 576..601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 601 AA; 66148 MW; EBF6FC6E0C64961B CRC64;
MPFKAFDTFK EKILKPGKEG VKNAVGDSLG ILQRKIDGTN EEEDAIELNE EGRPVQTSRA
HRPVCDCSCC GIPKRYICDC SCCGIPKRYI IAVMSGLGFC ISFGIRCNLG VAIVEMVNNS
TVYVDGKPEI QTAQFNWDPE TVGLIHGSFF WGYIVTQIPG GFISNKFAAS RVFGAAIFLT
STLNMFIPSA ARVHYGCVMG VRILQGLVEG VTYPACHGMW SKWAPPLERS RLATTSFCGS
YAGAVVAMPL AGVLVQYIGW ASVFYIYGMF GIIWYMFWLL QAYECPAAHP TISNAERTYI
ETSIGEGANL ASLSKFNTPW RRFFTSLPVY AIIVANFCRS WTFYLLLISQ PAYFEEVFGF
AISKVGLLSA VPHMVMTIVV PIGGQLADYL RSRKILTTTA VRKIMNCGGF GMEATLLLVV
GFSHTKGVAI SFLVLAVGFS GFAISGFNVN HLDIAPRYAS ILMGISNGVG TLSGMVCPLI
VGAMTKHKTR EEWQNVFLIA ALVHYSGVIF YGVFASGEKQ DWADPENLSE DKCGIIDQDE
LAEETELNHE TFVSPRKKMS YGATTQNCEV QKTEWRQQRE SAFDGEEPLS YQAEGDFSET
S
