Excitatory amino acid transporter 2

Details

Name
Excitatory amino acid transporter 2
Kind
protein
Synonyms
  • EAAT2
  • GLT1
  • Glutamate/aspartate transporter II
  • Sodium-dependent glutamate/aspartate transporter 2
  • Solute carrier family 1 member 2
Gene Name
SLC1A2
UniProtKB Entry
P43004Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0001762|Excitatory amino acid transporter 2
MASTEGANNMPKQVEVRMHDSHLGSEEPKHRHLGLRLCDKLGKNLLLTLTVFGVILGAVC
GGLLRLASPIHPDVVMLIAFPGDILMRMLKMLILPLIISSLITGLSGLDAKASGRLGTRA
MVYYMSTTIIAAVLGVILVLAIHPGNPKLKKQLGPGKKNDEVSSLDAFLDLIRNLFPENL
VQACFQQIQTVTKKVLVAPPPDEEANATSAVVSLLNETVTEVPEETKMVIKKGLEFKDGM
NVLGLIGFFIAFGIAMGKMGDQAKLMVDFFNILNEIVMKLVIMIMWYSPLGIACLICGKI
IAIKDLEVVARQLGMYMVTVIIGLIIHGGIFLPLIYFVVTRKNPFSFFAGIFQAWITALG
TASSAGTLPVTFRCLEENLGIDKRVTRFVLPVGATINMDGTALYEAVAAIFIAQMNGVVL
DGGQIVTVSLTATLASVGAASIPSAGLVTMLLILTAVGLPTEDISLLVAVDWLLDRMRTS
VNVVGDSFGAGIVYHLSKSELDTIDSQHRVHEDIEMTKTQSIYDDMKNHRESNSNQCVYA
AHNSVIVDECKVTLAANGKSADCSVEEEPWKREK
Number of residues
574
Molecular Weight
62103.665
Theoretical pI
6.51
GO Classification
Functions
cysteine transmembrane transporter activity / high-affinity L-glutamate transmembrane transporter activity / metal ion binding / monoatomic anion transmembrane transporter activity / neutral L-amino acid transmembrane transporter activity
Processes
cellular response to cocaine / chemical synaptic transmission / D-aspartate import across plasma membrane / glutathione biosynthetic process / L-aspartate import across plasma membrane / L-aspartate transmembrane transport / L-glutamate import across plasma membrane / monoatomic ion transport / neurotransmitter reuptake / neurotransmitter transport / protein homotrimerization / response to xenobiotic stimulus / transepithelial transport / transport across blood-brain barrier
Components
astrocyte projection / cell body / glutamatergic synapse / membrane protein complex / membrane raft / neuron projection terminus / presynaptic membrane / vesicle
General Function
Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:14506254, PubMed:15265858, PubMed:26690923, PubMed:7521911). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:14506254). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:14506254). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (By similarity)
Specific Function
cysteine transmembrane transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
45-64 88-108 121-142 236-259 269-296 318-339 385-411 472-493
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019025|Excitatory amino acid transporter 2 (SLC1A2)
ATGCCCAAGCAGGTGGAAGTGCGAATGCACGACAGTCATCTTGGCTCAGAGGAACCCAAG
CACCGGCACCTGGGCCTGCGCCTGTGTGACAAGCTGGGGAAGAATCTGCTGCTCACCCTG
ACGGTGTTTGGTGTCATCCTGGGAGCAGTGTGTGGAGGGCTTCTTCGCTTGGCATCTCCC
ATCCACCCTGATGTGGTTATGTTAATAGCCTTCCCAGGGGATATACTCATGAGGATGCTA
AAAATGCTCATTCTCCCTCTAATCATCTCCAGCTTAATCACAGGGTTGTCAGGCCTGGAT
GCTAAGGCTAGTGGCCGCTTGGGCACGAGAGCCATGGTGTATTACATGTCCACGACCATC
ATTGCTGCAGTACTGGGGGTCATTCTGGTCTTGGCTATCCATCCAGGCAATCCCAAGCTC
AAGAAGCAGCTGGGGCCTGGGAAGAAGAATGATGAAGTGTCCAGCCTGGATGCCTTCCTG
GACCTTATTCGAAATCTCTTCCCTGAAAACCTTGTCCAAGCCTGCTTTCAACAGATTCAA
ACAGTGACGAAGAAAGTCCTGGTTGCACCACCGCCGGACGAGGAGGCCAACGCAACCAGC
GCTGTTGTCTCTCTGTTGAACGAGACTGTGACTGAGGTGCCGGAGGAGACTAAGATGGTT
ATCAAGAAGGGCCTGGAGTTCAAGGATGGGATGAACGTCTTAGGTCTGATAGGGTTTTTC
ATTGCTTTTGGCATCGCTATGGGGAAGATGGGAGATCAGGCCAAGCTGATGGTGGATTTC
TTCAACATTTTGAATGAGATTGTAATGAAGTTAGTGATCATGATCATGTGGTACTCTCCC
CTGGGTATCGCCTGCCTGATCTGTGGAAAGATCATTGCAATCAAGGACTTAGAAGTGGTT
GCTAGGCAACTGGGGATGTACATGGTAACAGTGATCATAGGCCTCATCATCCACGGGGGC
ATCTTTCTCCCCTTGATTTACTTTGTAGTGACCAGGAAAAACCCCTTCTCCTTTTTTGCT
GGCATTTTCCAAGCTTGGATCACTGCCCTGGGCACCGCTTCCAGTGCTGGAACTTTGCCT
GTCACCTTTCGTTGCCTGGAAGAAAATCTGGGGATTGATAAGCGTGTGACTAGATTCGTC
CTTCCTGTTGGAGCAACCATTAACATGGATGGTACAGCCCTTTATGAAGCGGTAGCCGCC
ATCTTTATAGCCCAAATGAATGGTGTTGTCCTGGATGGAGGACAGATTGTGACTGTAAGC
CTCACAGCCACCCTGGCAAGCGTCGGCGCGGCCAGTATCCCCAGTGCCGGGCTGGTCACC
ATGCTCCTCATTCTGACAGCCGTGGGCCTGCCAACAGAGGACATCAGCCTGCTGGTGGCT
GTGGACTGGCTGCTGGACAGGATGAGAACTTCAGTCAATGTTGTGGGTGACTCTTTTGGG
GCTGGGATAGTCTATCACCTCTCCAAGTCTGAGCTGGATACCATTGACTCCCAGCATCGA
GTGCATGAAGATATTGAAATGACCAAGACTCAATCCATTTATGATGACATGAAGAACCAC
AGGGAAAGCAACTCTAATCAATGTGTCTATGCTGCACACAACTCTGTCATAGTAGATGAA
TGCAAGGTAACTCTGGCAGCCAATGGAAAGTCAGCCGACTGCAGTGTTGAGGAAGAACCT
TGGAAACGTGAGAAATAA
Chromosome Location
11
Locus
11p13
External Identifiers
ResourceLink
UniProtKB IDP43004
UniProtKB Entry NameEAA2_HUMAN
GenBank Protein ID487341
GenBank Gene IDU03505
GeneCard IDSLC1A2
GenAtlas IDSLC1A2
HGNC IDHGNC:10940
PDB ID(s)7VR7, 7VR8, 7XR4, 7XR6
KEGG IDhsa:6506
IUPHAR/Guide To Pharmacology ID869
NCBI Gene ID6506
General References
  1. Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG: Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci. 1994 Sep;14(9):5559-69. [Article]
  2. Shashidharan P, Wittenberg I, Plaitakis A: Molecular cloning of human brain glutamate/aspartate transporter II. Biochim Biophys Acta. 1994 May 11;1191(2):393-6. [Article]
  3. Manfras BJ, Rudert WA, Trucco M, Boehm BO: Cloning and characterization of a glutamate transporter cDNA from human brain and pancreas. Biochim Biophys Acta. 1994 Oct 12;1195(1):185-8. [Article]
  4. Shimamoto K, Lebrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T: DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Mol Pharmacol. 1998 Feb;53(2):195-201. [Article]
  5. Kim SY, Chao W, Choi SY, Volsky DJ: Cloning and characterization of the 3'-untranslated region of the human excitatory amino acid transporter 2 transcript. J Neurochem. 2003 Sep;86(6):1458-67. [Article]
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  7. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  9. Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C: A trimeric quaternary structure is conserved in bacterial and human glutamate transporters. J Biol Chem. 2004 Sep 17;279(38):39505-12. Epub 2004 Jul 20. [Article]
  10. Gebhardt FM, Mitrovic AD, Gilbert DF, Vandenberg RJ, Lynch JW, Dodd PR: Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2. J Biol Chem. 2010 Oct 8;285(41):31313-24. doi: 10.1074/jbc.M110.153494. Epub 2010 Aug 5. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Glutamic acidapproved, nutraceuticalunknowntargetDetails
Fingolimodapproved, investigationalunknowntransporterinducerDetails
Midazolamapproved, illicitnotransporterinhibitorDetails