L-穀氨酸-天門冬氨酸轉運體

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L-穀氨酸-天門冬氨酸轉運體
識別號
別名SLC1A3;, EA6, EAAT1, GLAST, GLAST1, solute carrier family 1 member 3
外部IDOMIM600111 MGI99917 HomoloGene20882 GeneCardsSLC1A3
相關疾病
episodic ataxia type 6[1]
為以下藥物的標靶
DL-TBOA[2]
基因位置(人類
5號染色體
染色體5號染色體[3]
5號染色體
L-穀氨酸-天門冬氨酸轉運體的基因位置
L-穀氨酸-天門冬氨酸轉運體的基因位置
基因座5p13.2起始36,596,588 bp[3]
終止36,688,334 bp[3]
RNA表達模式
查閱更多表達數據
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_001166695
​NM_001166696
​NM_001289939
​NM_001289940
​NM_004172

NM_148938

蛋白序列

NP_001160167
​NP_001160168
​NP_001276868
​NP_001276869
​NP_004163

NP_683740

基因位置​(UCSC)Chr 5: 36.6 – 36.69 MbChr 15: 8.66 – 8.74 Mb
PubMed​查找[5][6]
維基數據
檢視/編輯人類檢視/編輯小鼠

興奮性氨基酸轉運蛋白 1EAAT1 )是一種蛋白質,在人類中由SLC1A3基因編碼。 [7] EAAT1 也常被稱為穀氨酸天冬氨酸轉運蛋白 1 ( GLAST-1 )。

EAAT1 主要在質膜中表達,使其能夠從細胞外空間去除穀氨酸。 [8]它還位於線粒體內膜,並參與到蘋果酸穿梭的過程當中。 [9]

機制

EAAT1在體內以同型三聚體的形式發揮作用。 [10] EAAT1 介導穀氨酸天冬氨酸的運輸,其中包括三個Na +和一個H +陽離子同向運輸以及一個K +陽離子的反向運輸。這種共轉運偶聯作用(或同向轉運)允許穀氨酸逆着濃度梯度轉運到細胞內。 [11]

組織分佈

EAAT1 在整個中樞神經系統都有表達, [12]並且在小腦的星形膠質細胞伯格曼膠質細胞中高度表達。 [13] [14]在視網膜中,EAAT1 在穆勒細胞中表達。 [15] EAAT1 也在許多其他組織中表達,包括心肌細胞[9]

臨床意義

它與 6 型發作性共濟失調有關。 [16] EAAT1表達也可能與骨關節炎有關。 [17]

藥理

DL-蘇式-β-苄氧天冬氨酸 (TBOA) 是一種興奮性氨基酸轉運蛋白的抑制劑。 [18]

參考

  1. ^ 與L-穀氨酸-天門冬氨酸轉運體相關的疾病;在維基數據上查看/編輯參考. 
  2. ^ 對Solute carrier family 1 member 3起作用的藥物;在維基數據上查看/編輯參考. 
  3. ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000079215 - Ensembl, May 2017
  4. ^ 4.0 4.1 4.2 GRCm38: Ensembl release 89: ENSMUSG00000005360 - Ensembl, May 2017
  5. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  7. ^ Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3. 
  8. ^ Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC. Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. The Journal of Neuroscience. March 1995, 15 (3 Pt 1): 1835–53. PMC 6578153可免費查閱. PMID 7891138. doi:10.1523/JNEUROSCI.15-03-01835.1995. 
  9. ^ 9.0 9.1 Ralphe JC, Segar JL, Schutte BC, Scholz TD. Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria. Journal of Molecular and Cellular Cardiology. July 2004, 37 (1): 33–41. PMID 15242733. doi:10.1016/j.yjmcc.2004.04.008.  引用錯誤:帶有name屬性「pmid15242733」的<ref>標籤用不同內容定義了多次
  10. ^ 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. The Journal of Biological Chemistry. September 2004, 279 (38): 39505–12. PMID 15265858. S2CID 16077315. doi:10.1074/jbc.M408038200可免費查閱. 
  11. ^ Kanai Y, Hediger MA. The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflügers Archiv. February 2004, 447 (5): 469–79. PMID 14530974. S2CID 21564906. doi:10.1007/s00424-003-1146-4. 
  12. ^ Danbolt NC. Glutamate uptake. Progress in Neurobiology. September 2001, 65 (1): 1–105. PMID 11369436. S2CID 27347413. doi:10.1016/S0301-0082(00)00067-8. 
  13. ^ Storck T, Schulte S, Hofmann K, Stoffel W. Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Proceedings of the National Academy of Sciences of the United States of America. November 1992, 89 (22): 10955–9. Bibcode:1992PNAS...8910955S. PMC 50461可免費查閱. PMID 1279699. doi:10.1073/pnas.89.22.10955可免費查閱. 
  14. ^ Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW. Localization of neuronal and glial glutamate transporters. Neuron. September 1994, 13 (3): 713–25. PMID 7917301. S2CID 45299639. doi:10.1016/0896-6273(94)90038-8可免費查閱. 
  15. ^ Rauen T, Taylor WR, Kuhlbrodt K, Wiessner M. High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance. Cell and Tissue Research. January 1998, 291 (1): 19–31. PMID 9394040. S2CID 6814592. doi:10.1007/s004410050976. 
  16. ^ Jen JC, Wan J, Palos TP, Howard BD, Baloh RW. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Neurology. August 2005, 65 (4): 529–34. PMID 16116111. S2CID 22492395. doi:10.1212/01.WNL.0000172638.58172.5a. 
  17. ^ Mason DJ, Brakspear K, Wilson C, Williams R, Kotwal RS. Expression of glutamate receptors and transporters in human subchondral bone in osteoarthritis. Orthopaedic Proceedings (The British Editorial Society of Bone & Joint Surgery). July 2010, 93–B (SUPP_I): 411. doi:10.1302/0301-620X.93BSUPP_I.0930069b (不活躍 31 January 2024). 
  18. ^ 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. Molecular Pharmacology. February 1998, 53 (2): 195–201. PMID 9463476. doi:10.1124/mol.53.2.195.