VGLU2_HUMAN
ID VGLU2_HUMAN Reviewed; 582 AA.
AC Q9P2U8; A6NKS2;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Vesicular glutamate transporter 2 {ECO:0000303|PubMed:11698620};
DE Short=VGluT2 {ECO:0000303|PubMed:11698620};
DE AltName: Full=Differentiation-associated BNPI {ECO:0000303|PubMed:11698620};
DE AltName: Full=Differentiation-associated Na(+)-dependent inorganic phosphate cotransporter {ECO:0000303|PubMed:10820226};
DE AltName: Full=Solute carrier family 17 member 6;
GN Name=SLC17A6 {ECO:0000312|HGNC:HGNC:16703};
GN Synonyms=DNPI {ECO:0000303|PubMed:10820226},
GN VGLUT2 {ECO:0000303|PubMed:11698620};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Thalamus;
RX PubMed=10820226; DOI=10.1046/j.1471-4159.2000.0742622.x;
RA Aihara Y., Mashima H., Onda H., Hisano S., Kasuya H., Hori T., Yamada S.,
RA Tomura H., Yamada Y., Inoue I., Kojima I., Takeda J.;
RT "Molecular cloning of a novel brain-type Na(+)-dependent inorganic
RT phosphate cotransporter.";
RL J. Neurochem. 74:2622-2625(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=11698620; DOI=10.1523/jneurosci.21-22-j0002.2001;
RA Takamori S., Rhee J.S., Rosenmund C., Jahn R.;
RT "Identification of differentiation-associated brain-specific phosphate
RT transporter as a second vesicular glutamate transporter (VGLUT2).";
RL J. Neurosci. 21:RC182-RC182(2001).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=33440152; DOI=10.1016/j.celrep.2020.108623;
RA Cheret C., Ganzella M., Preobraschenski J., Jahn R., Ahnert-Hilger G.;
RT "Vesicular Glutamate Transporters (SLCA17 A6, 7, 8) Control Synaptic
RT Phosphate Levels.";
RL Cell Rep. 34:108623-108623(2021).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] SER-40.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Multifunctional transporter that transports L-glutamate as
CC well as multiple ions such as chloride, proton, potassium, sodium and
CC phosphate (PubMed:33440152, PubMed:11698620). At the synaptic vesicle
CC membrane, mainly functions as a uniporter which transports
CC preferentially L-glutamate but also, phosphate from the cytoplasm into
CC synaptic vesicles at presynaptic nerve terminals of excitatory neural
CC cells (PubMed:11698620). The L-glutamate or phosphate uniporter
CC activity is electrogenic and is driven by the proton electrochemical
CC gradient, mainly by the electrical gradient established by the vacuolar
CC H(+)-ATPase across the synaptic vesicle membrane (PubMed:11698620). In
CC addition, functions as a chloride channel that allows the chloride
CC permeation through the synaptic vesicle membrane therefore affects the
CC proton electrochemical gradient and promotes synaptic vesicles
CC acidification (By similarity). Moreover, functions as a vesicular
CC K(+)/H(+) antiport allowing to maintain the electrical gradient and to
CC decrease chemical gradient and therefore sustain vesicular glutamate
CC uptake (By similarity). The vesicular H(+)/H(+) antiport activity is
CC electroneutral (By similarity). 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 (Probable) (PubMed:10820226). The symporter
CC activity is driven by an inside negative membrane potential and is
CC electrogenic (Probable). Also involved in the regulation of retinal
CC hyaloid vessel regression during postnatal development (By similarity).
CC May also play a role in the endocrine glutamatergic system of other
CC tissues such as pineal gland and pancreas (By similarity).
CC {ECO:0000250|UniProtKB:Q8BLE7, ECO:0000250|UniProtKB:Q9JI12,
CC ECO:0000269|PubMed:10820226, ECO:0000269|PubMed:11698620,
CC ECO:0000305|PubMed:33440152}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(out) = L-glutamate(in); Xref=Rhea:RHEA:66336,
CC ChEBI:CHEBI:29985; Evidence={ECO:0000269|PubMed:11698620};
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:0000305|PubMed:33440152};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=phosphate(in) = phosphate(out); Xref=Rhea:RHEA:32823,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + K(+)(in) = H(+)(in) + K(+)(out);
CC Xref=Rhea:RHEA:29467, ChEBI:CHEBI:15378, ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- ACTIVITY REGULATION: Chloride channel activity is allosterically
CC activated by lumenal H(+) and Cl(-) leading to synaptic vesicles
CC acidification. The L-glutamate transport activity is allosterically
CC activated by lumenal H(+) and Cl(-). The allosteric requirement for
CC H(+) efficiently prevents non-vesicular efflux across the plasma
CC membrane. The L-glutamate uniporter activity exhibits a biphasic
CC dependence on chloride concentration. {ECO:0000250|UniProtKB:Q9JI12}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:11698620}; Multi-pass membrane
CC protein {ECO:0000255}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q8BLE7}. Cell membrane
CC {ECO:0000305|PubMed:33440152}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in adult brain
CC (PubMed:10820226). Expressed in amygdala, caudate nucleus, cerebral
CC cortex, frontal lobe, hippocampus, medulla, occipital lobe, putamen,
CC spinal cord, substantia nigra, subthalamic nucleus, temporal lobe and
CC thalamus (PubMed:10820226). {ECO:0000269|PubMed:10820226}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain.
CC {ECO:0000269|PubMed:10820226}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sodium/anion
CC cotransporter family. VGLUT subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB032435; BAA92874.1; -; mRNA.
DR EMBL; AC040936; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68324.1; -; Genomic_DNA.
DR EMBL; BC069629; AAH69629.1; -; mRNA.
DR EMBL; BC069640; AAH69640.1; -; mRNA.
DR EMBL; BC069646; AAH69646.1; -; mRNA.
DR CCDS; CCDS7856.1; -.
DR RefSeq; NP_065079.1; NM_020346.2.
DR AlphaFoldDB; Q9P2U8; -.
DR SMR; Q9P2U8; -.
DR BioGRID; 121355; 1.
DR STRING; 9606.ENSP00000263160; -.
DR TCDB; 2.A.1.14.31; the major facilitator superfamily (mfs).
DR GlyGen; Q9P2U8; 3 sites.
DR iPTMnet; Q9P2U8; -.
DR PhosphoSitePlus; Q9P2U8; -.
DR BioMuta; SLC17A6; -.
DR DMDM; 74734915; -.
DR MassIVE; Q9P2U8; -.
DR PaxDb; Q9P2U8; -.
DR PeptideAtlas; Q9P2U8; -.
DR PRIDE; Q9P2U8; -.
DR ProteomicsDB; 83899; -.
DR Antibodypedia; 25332; 238 antibodies from 31 providers.
DR DNASU; 57084; -.
DR Ensembl; ENST00000263160.4; ENSP00000263160.3; ENSG00000091664.9.
DR GeneID; 57084; -.
DR KEGG; hsa:57084; -.
DR MANE-Select; ENST00000263160.4; ENSP00000263160.3; NM_020346.3; NP_065079.1.
DR UCSC; uc001mqk.4; human.
DR CTD; 57084; -.
DR DisGeNET; 57084; -.
DR GeneCards; SLC17A6; -.
DR HGNC; HGNC:16703; SLC17A6.
DR HPA; ENSG00000091664; Tissue enriched (brain).
DR MIM; 607563; gene.
DR neXtProt; NX_Q9P2U8; -.
DR OpenTargets; ENSG00000091664; -.
DR PharmGKB; PA424; -.
DR VEuPathDB; HostDB:ENSG00000091664; -.
DR eggNOG; KOG2532; Eukaryota.
DR GeneTree; ENSGT00940000155891; -.
DR HOGENOM; CLU_001265_5_0_1; -.
DR InParanoid; Q9P2U8; -.
DR OMA; YNEQSQM; -.
DR OrthoDB; 497052at2759; -.
DR PhylomeDB; Q9P2U8; -.
DR TreeFam; TF313535; -.
DR PathwayCommons; Q9P2U8; -.
DR Reactome; R-HSA-428643; Organic anion transporters.
DR BioGRID-ORCS; 57084; 6 hits in 1067 CRISPR screens.
DR ChiTaRS; SLC17A6; human.
DR GenomeRNAi; 57084; -.
DR Pharos; Q9P2U8; Tbio.
DR PRO; PR:Q9P2U8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9P2U8; protein.
DR Bgee; ENSG00000091664; Expressed in lateral nuclear group of thalamus and 52 other tissues.
DR Genevisible; Q9P2U8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0060076; C:excitatory synapse; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
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:0022810; F:membrane potential driven uniporter activity; ISS:UniProtKB.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015386; F:potassium:proton antiporter activity; ISS:UniProtKB.
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:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0051938; P:L-glutamate import; IMP:UniProtKB.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; IMP:SynGO.
DR GO; GO:0055062; P:phosphate ion homeostasis; IDA:UniProtKB.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Antiport; Cell membrane; Chloride; Chloride channel; Cytoplasmic vesicle;
KW Glycoprotein; 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..582
FT /note="Vesicular glutamate transporter 2"
FT /id="PRO_0000318169"
FT TOPO_DOM 1..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..125
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 126..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..177
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..244
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..349
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 371..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 408..409
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..464
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 465..477
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..582
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 40
FT /note="T -> S (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_038710"
FT VARIANT 551
FT /note="N -> S (in dbSNP:rs7117340)"
FT /id="VAR_038711"
SQ SEQUENCE 582 AA; 64392 MW; CE761E56FA18C6AD CRC64;
MESVKQRILA PGKEGLKNFA GKSLGQIYRV LEKKQDTGET IELTEDGKPL EVPERKAPLC
DCTCFGLPRR YIIAIMSGLG FCISFGIRCN LGVAIVDMVN NSTIHRGGKV IKEKAKFNWD
PETVGMIHGS FFWGYIITQI PGGYIASRLA ANRVFGAAIL LTSTLNMLIP SAARVHYGCV
IFVRILQGLV EGVTYPACHG IWSKWAPPLE RSRLATTSFC GSYAGAVIAM PLAGILVQYT
GWSSVFYVYG SFGMVWYMFW LLVSYESPAK HPTITDEERR YIEESIGESA NLLGAMEKFK
TPWRKFFTSM PVYAIIVANF CRSWTFYLLL ISQPAYFEEV FGFEISKVGM LSAVPHLVMT
IIVPIGGQIA DFLRSKQILS TTTVRKIMNC GGFGMEATLL LVVGYSHTRG VAISFLVLAV
GFSGFAISGF NVNHLDIAPR YASILMGISN GVGTLSGMVC PIIVGAMTKN KSREEWQYVF
LIAALVHYGG VIFYAIFASG EKQPWADPEE TSEEKCGFIH EDELDEETGD ITQNYINYGT
TKSYGATTQA NGGWPSGWEK KEEFVQGEVQ DSHSYKDRVD YS
