VGLU3_RAT
ID VGLU3_RAT Reviewed; 588 AA.
AC Q7TSF2; Q8K1Q1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Vesicular glutamate transporter 3 {ECO:0000303|PubMed:12388773};
DE Short=VGluT3 {ECO:0000303|PubMed:12388773};
DE AltName: Full=Solute carrier family 17 member 8;
GN Name=Slc17a8 {ECO:0000312|RGD:628870}; Synonyms=Vglut3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=12097496; DOI=10.1523/jneurosci.22-13-05442.2002;
RA Gras C., Herzog E., Bellenchi G.C., Bernard V., Ravassard P., Pohl M.,
RA Gasnier B., Giros B., El Mestikawy S.;
RT "A third vesicular glutamate transporter expressed by cholinergic and
RT serotoninergic neurons.";
RL J. Neurosci. 22:5442-5451(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=12388773; DOI=10.1073/pnas.222546799;
RA Fremeau R.T. Jr., Burman J., Qureshi T., Tran C.H., Proctor J., Johnson J.,
RA Zhang H., Sulzer D., Copenhagen D.R., Storm-Mathisen J., Reimer R.J.,
RA Chaudhry F.A., Edwards R.H.;
RT "The identification of vesicular glutamate transporter 3 suggests novel
RT modes of signaling by glutamate.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14488-14493(2002).
RN [3]
RP TISSUE SPECIFICITY.
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=14751290; DOI=10.1016/j.neuroscience.2003.10.039;
RA Herzog E., Gilchrist J., Gras C., Muzerelle A., Ravassard P., Giros B.,
RA Gaspar P., El Mestikawy S.;
RT "Localization of VGLUT3, the vesicular glutamate transporter type 3, in the
RT rat brain.";
RL Neuroscience 123:983-1002(2004).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=15746915; DOI=10.1038/nn1397;
RA Gillespie D.C., Kim G., Kandler K.;
RT "Inhibitory synapses in the developing auditory system are glutamatergic.";
RL Nat. Neurosci. 8:332-338(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17110340; DOI=10.1016/j.cell.2006.10.030;
RA Takamori S., Holt M., Stenius K., Lemke E.A., Groenborg M., Riedel D.,
RA Urlaub H., Schenck S., Bruegger B., Ringler P., Mueller S.A., Rammner B.,
RA Graeter F., Hub J.S., De Groot B.L., Mieskes G., Moriyama Y., Klingauf J.,
RA Grubmueller H., Heuser J., Wieland F., Jahn R.;
RT "Molecular anatomy of a trafficking organelle.";
RL Cell 127:831-846(2006).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [8]
RP TISSUE SPECIFICITY.
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).
RN [9]
RP FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=27133463; DOI=10.1016/j.neuron.2016.03.026;
RA Eriksen J., Chang R., McGregor M., Silm K., Suzuki T., Edwards R.H.;
RT "Protons Regulate Vesicular Glutamate Transporters through an Allosteric
RT Mechanism.";
RL Neuron 90:768-780(2016).
CC -!- FUNCTION: Multifunctional transporter that transports L-glutamate as
CC well as multiple ions such as chloride, sodium and phosphate
CC (PubMed:12097496, PubMed:12388773, PubMed:27133463). 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:12097496, PubMed:12388773,
CC PubMed:27133463). 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:12388773, PubMed:12097496). In
CC addition, functions as a chloride channel that allows a chloride
CC permeation through the synaptic vesicle membrane that affects the
CC proton electrochemical gradient and promotes synaptic vesicles
CC acidification (PubMed:27133463). At the plasma membrane, following
CC exocytosis, functions as a symporter of Na(+) and phosphate from the
CC extracellular space to the cytoplasm allowing synaptic phosphate
CC homeostasis regulation (By similarity). The symporter activity is
CC electrogenic (By similarity). Moreover, operates synergistically with
CC SLC18A3/VACHT under a constant H(+) gradient, thereby allowing striatal
CC vesicular acetylcholine uptake (PubMed:18278042).
CC {ECO:0000250|UniProtKB:Q8NDX2, ECO:0000269|PubMed:12097496,
CC ECO:0000269|PubMed:12388773, ECO:0000269|PubMed:18278042,
CC ECO:0000269|PubMed:27133463}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(out) = L-glutamate(in); Xref=Rhea:RHEA:66336,
CC ChEBI:CHEBI:29985; Evidence={ECO:0000269|PubMed:12097496,
CC ECO:0000269|PubMed:12388773, ECO:0000269|PubMed:27133463};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:27133463};
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 -!- ACTIVITY REGULATION: The L-glutamate uniporter activity exhibits a
CC biphasic dependence on chloride concentration (PubMed:12388773).
CC Chloride channel activity is allosterically activated by lumenal H(+)
CC and Cl(-) leading to synaptic vesicles acidification (PubMed:27133463).
CC The glutamate transport activity is allosterically activated by lumenal
CC H(+) and Cl(-), preventing non-vesicular L-glutamate release
CC (PubMed:27133463). {ECO:0000269|PubMed:12388773,
CC ECO:0000269|PubMed:27133463}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.52 mM for L-glutamate {ECO:0000269|PubMed:12097496};
CC KM=1.5 mM for L-glutamate {ECO:0000269|PubMed:12388773};
CC Vmax=20.3 pmol/min/mg enzyme toward L-glutamate
CC {ECO:0000269|PubMed:12097496};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:12384506,
CC ECO:0000269|PubMed:12388773, ECO:0000305|PubMed:12097496}. Cell
CC membrane {ECO:0000250|UniProtKB:Q8NDX2}; Multi-pass membrane protein
CC {ECO:0000305}. Synapse, synaptosome {ECO:0000269|PubMed:12384506,
CC ECO:0000269|PubMed:12388773}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney and liver. Expressed
CC within the amygdala, brainstem, cerberal cortex, dorsal root ganglia,
CC dorsal spinal cord, hippocampus, hypothalamus, retina, striatum and
CC ventral spinal cord. Expressed within neurons of the caudate-putamen,
CC olfactory tubercle, nucleus accumbens, hippocampus, interpeduncular
CC nucleus and dorsal and medial raphe nuclei. Expressed in inner hair
CC cells of the ear. Expressed at synaptic terminals within the lateral
CC superior olive (LSO), a nucleus of the mammalian sound localization
CC system, and in the medial nucleus of the trapezoid body (MNTB), which
CC provides inhibitory input to the LSO. {ECO:0000269|PubMed:12097496,
CC ECO:0000269|PubMed:12384506, ECO:0000269|PubMed:12388773,
CC ECO:0000269|PubMed:14751290, ECO:0000269|PubMed:15746915,
CC ECO:0000269|PubMed:18215623}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sodium/anion
CC cotransporter family. VGLUT subfamily. {ECO:0000305}.
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DR EMBL; AJ491795; CAD37138.1; -; mRNA.
DR EMBL; AY117026; AAM50094.1; -; mRNA.
DR RefSeq; NP_714947.1; NM_153725.1.
DR AlphaFoldDB; Q7TSF2; -.
DR SMR; Q7TSF2; -.
DR STRING; 10116.ENSRNOP00000010207; -.
DR BindingDB; Q7TSF2; -.
DR ChEMBL; CHEMBL3472; -.
DR DrugCentral; Q7TSF2; -.
DR GlyGen; Q7TSF2; 1 site.
DR PaxDb; Q7TSF2; -.
DR PRIDE; Q7TSF2; -.
DR ABCD; Q7TSF2; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000092527; ENSRNOP00000075876; ENSRNOG00000007581.
DR GeneID; 266767; -.
DR KEGG; rno:266767; -.
DR UCSC; RGD:628870; rat.
DR CTD; 246213; -.
DR RGD; 628870; Slc17a8.
DR eggNOG; KOG2532; Eukaryota.
DR GeneTree; ENSGT00940000158187; -.
DR HOGENOM; CLU_001265_5_0_1; -.
DR InParanoid; Q7TSF2; -.
DR OMA; RRTTWGM; -.
DR OrthoDB; 497052at2759; -.
DR PhylomeDB; Q7TSF2; -.
DR TreeFam; TF313535; -.
DR Reactome; R-RNO-428643; Organic anion transporters.
DR PRO; PR:Q7TSF2; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000007581; Expressed in liver and 5 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0097441; C:basal dendrite; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0060076; C:excitatory synapse; IDA:RGD.
DR GO; GO:0097451; C:glial limiting end-foot; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:RGD.
DR GO; GO:0005771; C:multivesicular body; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:1990030; C:pericellular basket; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; ISO:RGD.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IDA: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; IEP:RGD.
DR GO; GO:0090102; P:cochlea development; IEP:RGD.
DR GO; GO:0051938; P:L-glutamate import; IMP:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IMP:UniProtKB.
DR GO; GO:0003407; P:neural retina development; IEP:RGD.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0051631; P:regulation of acetylcholine uptake; IDA: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;
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..588
FT /note="Vesicular glutamate transporter 3"
FT /id="PRO_0000331616"
FT TOPO_DOM 1..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..130
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..182
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..249
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 271..314
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..335
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 336..353
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 375..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..413
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 469..481
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 503..585
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 539..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 4
FT /note="N -> K (in Ref. 2; AAM50094)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 588 AA; 64755 MW; 9644C021D94286B5 CRC64;
MPFNAFDTFK EKILKPGKEG VKNAVGDSLG ILQRKLDGTN EEGDAIELSE EGRPVQTSRA
RAPVCDCSCC GIPKRYIIAV MSGLGFCISF GIRCNLGVAI VEMVNNSTVY VDGKPEIQTA
QFNWDPETVG LIHGSFFWGY IVTQIPGGFI SNKFAANRVF GAAIFLTSTL NMFIPSAARV
HYGCVMCVRI LQGLVEGVTY PACHGMWSKW APPLERSRLA TTSFCGSYAG AVVAMPLAGV
LVQYIGWASV FYIYGMFGII WYMFWLLQAY ECPAVHPTIS NEERTYIETS IGEGANLASL
SKFNTPWRRF FTSLPVYAII VANFCRSWTF YLLLISQPAY FEEVFGFAIS KVGLLSAVPH
MVMTIVVPIG GQLADYLRSR KILTTTAVRK IMNCGGFGME ATLLLVVGFS HTKGVAISFL
VLAVGFSGFA ISGFNVNHLD IAPRYASILM GISNGVGTLS GMVCPLIVGA MTKHKTREEW
QNVFLIAALV HYSGVIFYGV FASGEKQDWA DPENLSEEKC GIIDQDELAE ETELNHEAFV
SPRKKMSYGA TTQNCEVQKT DRRQQRESAF EGEEPLSYQN EEDFSETS
