Full text data of SLC1A6
SLC1A6
(EAAT4)
[Confidence: low (only semi-automatic identification from reviews)]
Excitatory amino acid transporter 4 (Sodium-dependent glutamate/aspartate transporter; Solute carrier family 1 member 6)
Excitatory amino acid transporter 4 (Sodium-dependent glutamate/aspartate transporter; Solute carrier family 1 member 6)
UniProt
P48664
ID EAA4_HUMAN Reviewed; 564 AA.
AC P48664;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 1.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Excitatory amino acid transporter 4;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter;
DE AltName: Full=Solute carrier family 1 member 6;
GN Name=SLC1A6; Synonyms=EAAT4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7791878; DOI=10.1038/375599a0;
RA Fairman W.A., Vandenberg R.J., Arriza J.L., Kavanaugh M.P.,
RA Amara S.G.;
RT "An excitatory amino-acid transporter with properties of a ligand-
RT gated chloride channel.";
RL Nature 375:599-603(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
CC -!- FUNCTION: Transports L-glutamate and also L- and D-aspartate.
CC Seems to act as a symport by cotransporting sodium.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Brain. Expressed densely and selectively in
CC cell bodies of Purkinje cells.
CC -!- SIMILARITY: Belongs to the sodium:dicarboxylate (SDF) symporter
CC (TC 2.A.23) family. SLC1A6 subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U18244; AAA75314.1; -; mRNA.
DR EMBL; AC004659; AAC15754.1; -; Genomic_DNA.
DR PIR; S58398; S58398.
DR RefSeq; NP_005062.1; NM_005071.2.
DR UniGene; Hs.515217; -.
DR UniGene; Hs.733178; -.
DR ProteinModelPortal; P48664; -.
DR SMR; P48664; 65-158, 250-519.
DR IntAct; P48664; 1.
DR STRING; 9606.ENSP00000221742; -.
DR BindingDB; P48664; -.
DR ChEMBL; CHEMBL3173; -.
DR DrugBank; DB00142; L-Glutamic Acid.
DR GuidetoPHARMACOLOGY; 871; -.
DR TCDB; 2.A.23.2.8; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.
DR PhosphoSite; P48664; -.
DR DMDM; 1352333; -.
DR PaxDb; P48664; -.
DR PRIDE; P48664; -.
DR Ensembl; ENST00000221742; ENSP00000221742; ENSG00000105143.
DR GeneID; 6511; -.
DR KEGG; hsa:6511; -.
DR UCSC; uc002naa.2; human.
DR CTD; 6511; -.
DR GeneCards; GC19M015060; -.
DR HGNC; HGNC:10944; SLC1A6.
DR HPA; HPA041505; -.
DR HPA; HPA044066; -.
DR MIM; 600637; gene.
DR neXtProt; NX_P48664; -.
DR PharmGKB; PA35831; -.
DR eggNOG; COG1301; -.
DR HOGENOM; HOG000208776; -.
DR HOVERGEN; HBG000080; -.
DR InParanoid; P48664; -.
DR KO; K05617; -.
DR OMA; DVEHYNA; -.
DR OrthoDB; EOG7RV9G2; -.
DR PhylomeDB; P48664; -.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_19419; Amino acid and oligopeptide SLC transporters.
DR GeneWiki; Excitatory_amino-acid_transporter_4; -.
DR GenomeRNAi; 6511; -.
DR NextBio; 25319; -.
DR PRO; PR:P48664; -.
DR ArrayExpress; P48664; -.
DR Bgee; P48664; -.
DR CleanEx; HS_SLC1A6; -.
DR Genevestigator; P48664; -.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0015183; F:L-aspartate transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0017153; F:sodium:dicarboxylate symporter activity; IEA:InterPro.
DR GO; GO:0015813; P:L-glutamate transport; TAS:ProtInc.
DR GO; GO:0042391; P:regulation of membrane potential; IEA:Ensembl.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR InterPro; IPR001991; Na-dicarboxylate_symporter.
DR InterPro; IPR018107; Na-dicarboxylate_symporter_CS.
DR PANTHER; PTHR11958; PTHR11958; 1.
DR Pfam; PF00375; SDF; 1.
DR PRINTS; PR00173; EDTRNSPORT.
DR PROSITE; PS00713; NA_DICARBOXYL_SYMP_1; 1.
DR PROSITE; PS00714; NA_DICARBOXYL_SYMP_2; 1.
PE 2: Evidence at transcript level;
KW Complete proteome; Glycoprotein; Membrane; Reference proteome;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 564 Excitatory amino acid transporter 4.
FT /FTId=PRO_0000202070.
FT TOPO_DOM 1 55 Cytoplasmic (Potential).
FT TRANSMEM 56 76 Helical; (Potential).
FT TRANSMEM 99 119 Helical; (Potential).
FT TRANSMEM 133 153 Helical; (Potential).
FT TOPO_DOM 154 264 Extracellular (Potential).
FT TRANSMEM 265 285 Helical; (Potential).
FT TRANSMEM 306 326 Helical; (Potential).
FT TRANSMEM 345 365 Helical; (Potential).
FT TRANSMEM 370 390 Helical; (Potential).
FT TRANSMEM 418 438 Helical; (Potential).
FT TRANSMEM 460 480 Helical; (Potential).
FT TRANSMEM 481 501 Helical; (Potential).
FT CARBOHYD 216 216 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 232 232 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 239 239 N-linked (GlcNAc...) (Potential).
SQ SEQUENCE 564 AA; 61565 MW; BB6700D6EAEC2B20 CRC64;
MSSHGNSLFL RESGQRLGRV GWLQRLQESL QQRALRTRLR LQTMTLEHVL RFLRRNAFIL
LTVSAVVIGV SLAFALRPYQ LTYRQIKYFS FPGELLMRML QMLVLPLIVS SLVTGMASLD
NKATGRMGMR AAVYYMVTTI IAVFIGILMV TIIHPGKGSK EGLHREGRIE TIPTADAFMD
LIRNMFPPNL VEACFKQFKT QYSTRVVTRT MVRTENGSEP GASMPPPFSV ENGTSFLENV
TRALGTLQEM LSFEETVPVP GSANGINALG LVVFSVAFGL VIGGMKHKGR VLRDFFDSLN
EAIMRLVGII IWYAPVGILF LIAGKILEME DMAVLGGQLG MYTLTVIVGL FLHAGIVLPL
IYFLVTHRNP FPFIGGMLQA LITAMGTSSS SATLPITFRC LEEGLGVDRR ITRFVLPVGA
TVNMDGTALY EALAAIFIAQ VNNYELNLGQ ITTISITATA ASVGAAGIPQ AGLVTMVIVL
TSVGLPTEDI TLIIAVDWFL DRLRTMTNVL GDSIGAAVIE HLSQRELELQ EAELTLPSLG
KPYKSLMAQE KGASRGRGGN ESAM
//
ID EAA4_HUMAN Reviewed; 564 AA.
AC P48664;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 1.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Excitatory amino acid transporter 4;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter;
DE AltName: Full=Solute carrier family 1 member 6;
GN Name=SLC1A6; Synonyms=EAAT4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7791878; DOI=10.1038/375599a0;
RA Fairman W.A., Vandenberg R.J., Arriza J.L., Kavanaugh M.P.,
RA Amara S.G.;
RT "An excitatory amino-acid transporter with properties of a ligand-
RT gated chloride channel.";
RL Nature 375:599-603(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
CC -!- FUNCTION: Transports L-glutamate and also L- and D-aspartate.
CC Seems to act as a symport by cotransporting sodium.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Brain. Expressed densely and selectively in
CC cell bodies of Purkinje cells.
CC -!- SIMILARITY: Belongs to the sodium:dicarboxylate (SDF) symporter
CC (TC 2.A.23) family. SLC1A6 subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U18244; AAA75314.1; -; mRNA.
DR EMBL; AC004659; AAC15754.1; -; Genomic_DNA.
DR PIR; S58398; S58398.
DR RefSeq; NP_005062.1; NM_005071.2.
DR UniGene; Hs.515217; -.
DR UniGene; Hs.733178; -.
DR ProteinModelPortal; P48664; -.
DR SMR; P48664; 65-158, 250-519.
DR IntAct; P48664; 1.
DR STRING; 9606.ENSP00000221742; -.
DR BindingDB; P48664; -.
DR ChEMBL; CHEMBL3173; -.
DR DrugBank; DB00142; L-Glutamic Acid.
DR GuidetoPHARMACOLOGY; 871; -.
DR TCDB; 2.A.23.2.8; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.
DR PhosphoSite; P48664; -.
DR DMDM; 1352333; -.
DR PaxDb; P48664; -.
DR PRIDE; P48664; -.
DR Ensembl; ENST00000221742; ENSP00000221742; ENSG00000105143.
DR GeneID; 6511; -.
DR KEGG; hsa:6511; -.
DR UCSC; uc002naa.2; human.
DR CTD; 6511; -.
DR GeneCards; GC19M015060; -.
DR HGNC; HGNC:10944; SLC1A6.
DR HPA; HPA041505; -.
DR HPA; HPA044066; -.
DR MIM; 600637; gene.
DR neXtProt; NX_P48664; -.
DR PharmGKB; PA35831; -.
DR eggNOG; COG1301; -.
DR HOGENOM; HOG000208776; -.
DR HOVERGEN; HBG000080; -.
DR InParanoid; P48664; -.
DR KO; K05617; -.
DR OMA; DVEHYNA; -.
DR OrthoDB; EOG7RV9G2; -.
DR PhylomeDB; P48664; -.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_19419; Amino acid and oligopeptide SLC transporters.
DR GeneWiki; Excitatory_amino-acid_transporter_4; -.
DR GenomeRNAi; 6511; -.
DR NextBio; 25319; -.
DR PRO; PR:P48664; -.
DR ArrayExpress; P48664; -.
DR Bgee; P48664; -.
DR CleanEx; HS_SLC1A6; -.
DR Genevestigator; P48664; -.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0015183; F:L-aspartate transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0017153; F:sodium:dicarboxylate symporter activity; IEA:InterPro.
DR GO; GO:0015813; P:L-glutamate transport; TAS:ProtInc.
DR GO; GO:0042391; P:regulation of membrane potential; IEA:Ensembl.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR InterPro; IPR001991; Na-dicarboxylate_symporter.
DR InterPro; IPR018107; Na-dicarboxylate_symporter_CS.
DR PANTHER; PTHR11958; PTHR11958; 1.
DR Pfam; PF00375; SDF; 1.
DR PRINTS; PR00173; EDTRNSPORT.
DR PROSITE; PS00713; NA_DICARBOXYL_SYMP_1; 1.
DR PROSITE; PS00714; NA_DICARBOXYL_SYMP_2; 1.
PE 2: Evidence at transcript level;
KW Complete proteome; Glycoprotein; Membrane; Reference proteome;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 564 Excitatory amino acid transporter 4.
FT /FTId=PRO_0000202070.
FT TOPO_DOM 1 55 Cytoplasmic (Potential).
FT TRANSMEM 56 76 Helical; (Potential).
FT TRANSMEM 99 119 Helical; (Potential).
FT TRANSMEM 133 153 Helical; (Potential).
FT TOPO_DOM 154 264 Extracellular (Potential).
FT TRANSMEM 265 285 Helical; (Potential).
FT TRANSMEM 306 326 Helical; (Potential).
FT TRANSMEM 345 365 Helical; (Potential).
FT TRANSMEM 370 390 Helical; (Potential).
FT TRANSMEM 418 438 Helical; (Potential).
FT TRANSMEM 460 480 Helical; (Potential).
FT TRANSMEM 481 501 Helical; (Potential).
FT CARBOHYD 216 216 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 232 232 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 239 239 N-linked (GlcNAc...) (Potential).
SQ SEQUENCE 564 AA; 61565 MW; BB6700D6EAEC2B20 CRC64;
MSSHGNSLFL RESGQRLGRV GWLQRLQESL QQRALRTRLR LQTMTLEHVL RFLRRNAFIL
LTVSAVVIGV SLAFALRPYQ LTYRQIKYFS FPGELLMRML QMLVLPLIVS SLVTGMASLD
NKATGRMGMR AAVYYMVTTI IAVFIGILMV TIIHPGKGSK EGLHREGRIE TIPTADAFMD
LIRNMFPPNL VEACFKQFKT QYSTRVVTRT MVRTENGSEP GASMPPPFSV ENGTSFLENV
TRALGTLQEM LSFEETVPVP GSANGINALG LVVFSVAFGL VIGGMKHKGR VLRDFFDSLN
EAIMRLVGII IWYAPVGILF LIAGKILEME DMAVLGGQLG MYTLTVIVGL FLHAGIVLPL
IYFLVTHRNP FPFIGGMLQA LITAMGTSSS SATLPITFRC LEEGLGVDRR ITRFVLPVGA
TVNMDGTALY EALAAIFIAQ VNNYELNLGQ ITTISITATA ASVGAAGIPQ AGLVTMVIVL
TSVGLPTEDI TLIIAVDWFL DRLRTMTNVL GDSIGAAVIE HLSQRELELQ EAELTLPSLG
KPYKSLMAQE KGASRGRGGN ESAM
//
MIM
600637
*RECORD*
*FIELD* NO
600637
*FIELD* TI
*600637 SOLUTE CARRIER FAMILY 1 (HIGH AFFINITY ASPARTATE/GLUTAMATE TRANSPORTER),
MEMBER 6; SLC1A6
read more;;EXCITATORY AMINO ACID TRANSPORTER 4; EAAT4
*FIELD* TX
CLONING
Excitatory amino acid transporters (EAATs) in the central nervous system
maintain extracellular glutamate concentrations below excitotoxic levels
and may limit the activation of glutamate receptors. Fairman et al.
(1995) cloned a novel human aspartate/glutamate transporter, which they
designated EAAT4, that is expressed predominantly in the cerebellum. The
transport activity encoded by EAAT4 has high apparent affinity for
L-aspartate and L-glutamate, and has a pharmacologic profile consistent
with previously described cerebellar transport activities.
Fairman et al. (1995) found that the amino acid sequence predicted by
the EAAT4 cDNAs exhibited 65%, 41%, and 48% sequence identity with the
human glutamate transporters EAAT1 (600111), EAAT2 (600300), and EAAT3
(133550), respectively, and did not correspond to any previously
isolated glutamate transporter subtype.
GENE FUNCTION
Fairman et al. (1995) found that in Xenopus oocytes expressing EAAT4,
L-aspartate and L-glutamate elicited a current predominantly carried by
chloride ions. This chloride conductance was not blocked by components
that block endogenous oocyte chloride channels. Thus, Fairman et al.
(1995) found that EAAT4 combines the reuptake of neurotransmitter with a
mechanism for increasing chloride permeability, both of which could
regulate excitatory neurotransmission.
Jackson et al. (2001) used a yeast 2-hybrid screen to identify proteins
that interact with the carboxy 77 amino acids of EAAT4. GTRAP41 (SPTBN2;
604985) and GTRAP48 (605708) increase glutamate transport, and their
coexpression results in further increase in glutamate uptake. Kinetic
analysis indicated that GTRAP41 and GTRAP48 produced an increase in the
V(max) of glutamate transport activity. GTRAP41 and GTRAP48 may
therefore enhance glutamate transport either through an increase in
catalytic rate of the transporter or through an increase in cell surface
availability. GTRAP41 and GTRAP48 were found to stabilize and/or anchor
EAAT4 to cell membranes, making it less likely to be internalized and
subsequently degraded. The EAAT4/GTRAP48 interaction was important in
modulating EAAT4 uptake activity. Since GTRAP48 was found to activate
Rho, Jackson et al. (2001) concluded that their findings implicate a
role for G protein signaling, a pathway that may involve Rho activation,
and anchoring to the actin cytoskeleton. GTRAP41 and GTRAP48 may also
modulate the perisynaptic distribution of EAAT4 at glutamatergic
synapses.
*FIELD* RF
1. Fairman, W. A.; Vandenberg, R. J.; Arriza, J. L.; Kavanaugh, M.
P.; Amara, S. G.: An excitatory amino-acid transporter with properties
of a ligand-gated chloride channel. Nature 375: 599-603, 1995.
2. Jackson, M.; Song, W.; Liu, M.-Y.; Jin, L.; Dykes-Hoberg, M.; Lin,
C. G.; Bowers, W. J.; Federoff, H. J.; Sternweis, P. C.; Rothstein,
J. D.: Modulation of the neuronal glutamate transporter EAAT4 by
two interacting proteins. Nature 410: 89-93, 2001.
*FIELD* CN
Ada Hamosh - updated: 2/28/2001
*FIELD* CD
Victor A. McKusick: 7/6/1995
*FIELD* ED
carol: 12/21/2010
carol: 8/9/2007
carol: 3/8/2002
terry: 3/8/2002
alopez: 2/28/2001
terry: 2/28/2001
psherman: 4/20/1999
dkim: 9/11/1998
mark: 2/5/1997
mark: 2/22/1996
mark: 7/6/1995
*RECORD*
*FIELD* NO
600637
*FIELD* TI
*600637 SOLUTE CARRIER FAMILY 1 (HIGH AFFINITY ASPARTATE/GLUTAMATE TRANSPORTER),
MEMBER 6; SLC1A6
read more;;EXCITATORY AMINO ACID TRANSPORTER 4; EAAT4
*FIELD* TX
CLONING
Excitatory amino acid transporters (EAATs) in the central nervous system
maintain extracellular glutamate concentrations below excitotoxic levels
and may limit the activation of glutamate receptors. Fairman et al.
(1995) cloned a novel human aspartate/glutamate transporter, which they
designated EAAT4, that is expressed predominantly in the cerebellum. The
transport activity encoded by EAAT4 has high apparent affinity for
L-aspartate and L-glutamate, and has a pharmacologic profile consistent
with previously described cerebellar transport activities.
Fairman et al. (1995) found that the amino acid sequence predicted by
the EAAT4 cDNAs exhibited 65%, 41%, and 48% sequence identity with the
human glutamate transporters EAAT1 (600111), EAAT2 (600300), and EAAT3
(133550), respectively, and did not correspond to any previously
isolated glutamate transporter subtype.
GENE FUNCTION
Fairman et al. (1995) found that in Xenopus oocytes expressing EAAT4,
L-aspartate and L-glutamate elicited a current predominantly carried by
chloride ions. This chloride conductance was not blocked by components
that block endogenous oocyte chloride channels. Thus, Fairman et al.
(1995) found that EAAT4 combines the reuptake of neurotransmitter with a
mechanism for increasing chloride permeability, both of which could
regulate excitatory neurotransmission.
Jackson et al. (2001) used a yeast 2-hybrid screen to identify proteins
that interact with the carboxy 77 amino acids of EAAT4. GTRAP41 (SPTBN2;
604985) and GTRAP48 (605708) increase glutamate transport, and their
coexpression results in further increase in glutamate uptake. Kinetic
analysis indicated that GTRAP41 and GTRAP48 produced an increase in the
V(max) of glutamate transport activity. GTRAP41 and GTRAP48 may
therefore enhance glutamate transport either through an increase in
catalytic rate of the transporter or through an increase in cell surface
availability. GTRAP41 and GTRAP48 were found to stabilize and/or anchor
EAAT4 to cell membranes, making it less likely to be internalized and
subsequently degraded. The EAAT4/GTRAP48 interaction was important in
modulating EAAT4 uptake activity. Since GTRAP48 was found to activate
Rho, Jackson et al. (2001) concluded that their findings implicate a
role for G protein signaling, a pathway that may involve Rho activation,
and anchoring to the actin cytoskeleton. GTRAP41 and GTRAP48 may also
modulate the perisynaptic distribution of EAAT4 at glutamatergic
synapses.
*FIELD* RF
1. Fairman, W. A.; Vandenberg, R. J.; Arriza, J. L.; Kavanaugh, M.
P.; Amara, S. G.: An excitatory amino-acid transporter with properties
of a ligand-gated chloride channel. Nature 375: 599-603, 1995.
2. Jackson, M.; Song, W.; Liu, M.-Y.; Jin, L.; Dykes-Hoberg, M.; Lin,
C. G.; Bowers, W. J.; Federoff, H. J.; Sternweis, P. C.; Rothstein,
J. D.: Modulation of the neuronal glutamate transporter EAAT4 by
two interacting proteins. Nature 410: 89-93, 2001.
*FIELD* CN
Ada Hamosh - updated: 2/28/2001
*FIELD* CD
Victor A. McKusick: 7/6/1995
*FIELD* ED
carol: 12/21/2010
carol: 8/9/2007
carol: 3/8/2002
terry: 3/8/2002
alopez: 2/28/2001
terry: 2/28/2001
psherman: 4/20/1999
dkim: 9/11/1998
mark: 2/5/1997
mark: 2/22/1996
mark: 7/6/1995