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维基百科

前類澱粉蛋白質

行進 31, 2023

前類澱粉蛋白質 (英語: Amyloid precursor protein, APP) 是一個細胞膜內嵌蛋白，在很多組織都能找到，但主要集中在神經元的突觸。一般認為前類澱粉蛋白質能夠調控突觸的形成,[2] 神经可塑性[3]及排出鐵原子[4]，但其主要功能仍然未明。

Amyloid beta (A4) precursor protein
PDB rendering based on 1aap[1]
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 APP; AAA; ABETA; ABPP; AD1; APPI; CTFgamma; CVAP; PN-II; PN2
扩展标识 遗传学：104760 鼠基因：88059 同源基因：56379 ChEMBL: 2487 GeneCards: APP Gene
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 351 11820
Ensembl ENSG00000142192 ENSMUSG00000022892
UniProt P05067 P12023
mRNA序列 NM_000484 NM_001198823
蛋白序列 NP_000475 NP_001185752
基因位置 Chr 21:
25.88 – 26.17 Mb		 Chr 16:
84.95 – 85.17 Mb
PubMed查询 [1] [2]
類澱粉蛋白的生成被廣泛認為是由前類澱粉蛋白質經蛋白酶解所產生。類澱粉蛋白是一個由37 至49顆氨基酸所組成的不可溶的纖維性蛋白質，其沉積之後形成的類澱粉蛋白斑能夠在阿兹海默症病人的大腦中被找到，並被認為是很多神經性疾病的病因。

基因學

前類澱粉蛋白質表達於很多不同的物種而且高度保守[5]。 其基因序列位於人類第21號染色體，擁有290,000個鹼基對而組成18個外顯子。[6][7] 在人體中，基於選擇性剪接，前類澱粉蛋白質有幾個等位蛋白（英语：Protein isoform），長度由365至770個氨基酸不等，其中一些等位蛋白主要於神經元表達。等位蛋白間比例的改變被認為與阿兹海默症有關。[8] 同源蛋白存在於果蠅，秀麗隱桿線蟲與及所有哺乳類。[9] 不過，位處細胞膜間的類澱粉蛋白並不高度保守於物種間，亦與前類澱粉蛋白質的生物功能沒有明顯關係。[9]

某些基因突變如果發生在前類澱粉蛋白質的重要位置，包括但不限於發生在類澱粉蛋白序列組中，就會增加患上遺傳性阿兹海默症的機會。[10][11][12]例如一些發生在類澱粉蛋白序列外面的基因突變就被認為導致類澱粉蛋白增長。[13]

亦有些基因突變，例如是A673T，就被認為能減低患上阿兹海默症的機會。這個突變位於 beta secretase cleavage site，理論上能經由減低beta C-Terminus fragment 而抑壓類澱粉蛋白的生成。證據顯示於試管內能減低40% 類澱粉蛋白生成。[14]

參閱

  • 彈震症（英语：Shell shock）(shell shock)

外部連結

  1. ^ Hynes TR, Randal M, Kennedy LA, Eigenbrot C, Kossiakoff AA. X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor. Biochemistry. Oct 1990, 29 (43): 10018–22. PMID 2125487. doi:10.1021/bi00495a002. 
  2. ^ Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J. Synapse formation and function is modulated by the amyloid precursor protein. The Journal of Neuroscience. Jul 2006, 26 (27): 7212–21. PMID 16822978. doi:10.1523/JNEUROSCI.1450-06.2006. 
  3. ^ Turner PR, O'Connor K, Tate WP, Abraham WC. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Progress in Neurobiology. May 2003, 70 (1): 1–32. PMID 12927332. doi:10.1016/S0301-0082(03)00089-3. 
  4. ^ Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI. Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell. Sep 2010, 142 (6): 857–67. PMC 2943017  . PMID 20817278. doi:10.1016/j.cell.2010.08.014. 
  5. ^ Tharp WG, Sarkar IN. Origins of amyloid-β. BMC Genomics. April 2013, 14 (1): 290. PMID 23627794. doi:10.1186/1471-2164-14-290. 
  6. ^ Yoshikai S, Sasaki H, Doh-ura K, Furuya H, Sakaki Y. Genomic organization of the human amyloid beta-protein precursor gene. Gene. Mar 1990, 87 (2): 257–63. PMID 2110105. doi:10.1016/0378-1119(90)90310-N. 
  7. ^ Lamb BT, Sisodia SS, Lawler AM, Slunt HH, Kitt CA, Kearns WG, Pearson PL, Price DL, Gearhart JD. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected]. Nature Genetics. Sep 1993, 5 (1): 22–30. PMID 8220418. doi:10.1038/ng0993-22. 
  8. ^ Matsui T, Ingelsson M, Fukumoto H, Ramasamy K, Kowa H, Frosch MP, Irizarry MC, Hyman BT. Expression of APP pathway mRNAs and proteins in Alzheimer's disease. Brain Research. Aug 2007, 1161: 116–23. PMID 17586478. doi:10.1016/j.brainres.2007.05.050. 
  9. ^ 9.0 9.1 Zheng H, Koo EH. The amyloid precursor protein: beyond amyloid. Molecular Neurodegeneration. 2006, 1 (1): 5. PMC 1538601  . PMID 16930452. doi:10.1186/1750-1326-1-5. 
  10. ^ Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. Feb 1991, 349 (6311): 704–6. PMID 1671712. doi:10.1038/349704a0. 
  11. ^ Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science. Oct 1991, 254 (5028): 97–9. PMID 1925564. doi:10.1126/science.1925564. 
  12. ^ Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature. Oct 1991, 353 (6347): 844–6. PMID 1944558. doi:10.1038/353844a0. 
  13. ^ Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature. Dec 1992, 360 (6405): 672–4. PMID 1465129. doi:10.1038/360672a0. 
  14. ^ Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, Hoyte K, Gustafson A, Liu Y, Lu Y, Bhangale T, Graham RR, Huttenlocher J, Bjornsdottir G, Andreassen OA, Jönsson EG, Palotie A, Behrens TW, Magnusson OT, Kong A, Thorsteinsdottir U, Watts RJ, Stefansson K. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature. Aug 2012, 488 (7409): 96–9. PMID 22801501. doi:10.1038/nature11283. （原始内容于2020-11-12） 使用|archiveurl=需要含有|url= (帮助). 简明摘要 – The New York Times. 

行進 31, 2023
前類澱粉蛋白質, 英語, amyloid, precursor, protein, 是一個細胞膜內嵌蛋白, 在很多組織都能找到, 但主要集中在神經元的突觸, 一般認為能夠調控突觸的形成, 神经可塑性, 及排出鐵原子, 但其主要功能仍然未明, amyloid, beta, precursor, proteinpdb, rendering, based, 1aap, 有效结构pdb, 直系同源检索, pdbe, rcsbpdb查询代码列表1aap, 1amb, 1amc, 1aml, 1ba4, 1ba6, 1bjb,. 前類澱粉蛋白質 英語 Amyloid precursor protein APP 是一個細胞膜內嵌蛋白 在很多組織都能找到 但主要集中在神經元的突觸 一般認為前類澱粉蛋白質能夠調控突觸的形成 2 神经可塑性 3 及排出鐵原子 4 但其主要功能仍然未明 Amyloid beta A4 precursor proteinPDB rendering based on 1aap 1 有效结构PDB 直系同源检索 PDBe RCSBPDB查询代码列表1AAP 1AMB 1AMC 1AML 1BA4 1BA6 1BJB 1BJC 1BRC 1CA0 1HZ3 1IYT 1MWP 1OWT 1QCM 1QWP 1QXC 1QYT 1TAW 1TKN 1UO7 1UO8 1UOA 1UOI 1X11 1Z0Q 1ZE7 1ZE9 1ZJD 2BEG 2BOM 2BP4 2FJZ 2FK1 2FK2 2FK3 2FKL 2FMA 2G47 2IPU 2LFM 2LLM 2LMN 2LMO 2LMP 2LMQ 2LNQ 2LOH 2LP1 2LZ3 2LZ4 2M4J 2M9R 2M9S 2MGT 2MJ1 2MPZ 2MVX 2MXU 2OTK 2R0W 2WK3 2Y29 2Y2A 2Y3J 2Y3K 2Y3L 3AYU 3BAE 3BKJ 3DXC 3DXD 3DXE 3GCI 3IFL 3IFN 3IFO 3IFP 3JQ5 3JQL 3JTI 3KTM 3L33 3L81 3MOQ 3MXC 3MXY 3NYJ 3NYL 3OVJ 3OW9 3SV1 3U0T 3UMH 3UMI 3UMK 4HIX 4JFN 4M1C 4MDR 4NGE 4OJF 4ONF 4ONG 4PQD 4PWQ标识代号APP AAA ABETA ABPP AD1 APPI CTFgamma CVAP PN II PN2扩展标识遗传学 104760 鼠基因 88059 同源基因 56379 ChEMBL 2487 GeneCards APP Gene基因本体论描述分子功能 DNA binding serine type endopeptidase inhibitor activity receptor binding protein binding heparin binding peptidase activator activity enzyme binding acetylcholine receptor binding identical protein binding transition metal ion binding PTB domain binding growth factor receptor binding细胞成分 extracellular region extracellular space nuclear envelope lumen cytoplasm endosome smooth endoplasmic reticulum Golgi apparatus cytosol plasma membrane integral component of plasma membrane coated pit cell cell junction cell surface integral component of membrane ER to Golgi transport vesicle axon platelet alpha granule lumen neuromuscular junction endosome lumen trans Golgi network membrane ciliary rootlet terminal bouton dendritic spine dendritic shaft intracellular membrane bounded organelle receptor complex membrane raft apical part of cell synapse perinuclear region of cytoplasm spindle midzone extracellular exosome生物过程 suckling behavior platelet degranulation mRNA polyadenylation regulation of translation protein phosphorylation cellular copper ion homeostasis post Golgi vesicle mediated transport endocytosis response to oxidative stress cell adhesion regulation of epidermal growth factor activated receptor activity Notch signaling pathway axonogenesis blood coagulation mating behavior locomotory behavior axon cargo transport cholesterol metabolic process adult locomotory behavior visual learning negative regulation of endopeptidase activity positive regulation of peptidase activity positive regulation of G2 M transition of mitotic cell cycle axon midline choice point recognition neuron remodeling dendrite development platelet activation extracellular matrix organization forebrain development neuron projection development ionotropic glutamate receptor signaling pathway nucleotide binding domain leucine rich repeat containing receptor signaling pathway regulation of multicellular organism growth regulation of protein binding innate immune response negative regulation of neuron differentiation positive regulation of mitotic cell cycle positive regulation of transcription from RNA polymerase II promoter collateral sprouting in absence of injury regulation of synapse structure or activity neuromuscular process controlling balance synaptic growth at neuromuscular junction neuron apoptotic process smooth endoplasmic reticulum calcium ion homeostasis membrane organizationSources Amigo QuickGORNA表达模式更多表达数据直系同源体物种人类小鼠Entrez35111820EnsemblENSG00000142192ENSMUSG00000022892UniProtP05067P12023mRNA序列NM 000484NM 001198823蛋白序列NP 000475NP 001185752基因位置Chr 21 25 88 26 17 MbChr 16 84 95 85 17 MbPubMed查询 1 2 查论编類澱粉蛋白的生成被廣泛認為是由前類澱粉蛋白質經蛋白酶解所產生 類澱粉蛋白是一個由37 至49顆氨基酸所組成的不可溶的纖維性蛋白質 其沉積之後形成的類澱粉蛋白斑能夠在阿兹海默症病人的大腦中被找到 並被認為是很多神經性疾病的病因 基因學 编辑前類澱粉蛋白質表達於很多不同的物種而且高度保守 5 其基因序列位於人類第21號染色體 擁有290 000個鹼基對而組成18個外顯子 6 7 在人體中 基於選擇性剪接 前類澱粉蛋白質有幾個等位蛋白 英语 Protein isoform 長度由365至770個氨基酸不等 其中一些等位蛋白主要於神經元表達 等位蛋白間比例的改變被認為與阿兹海默症有關 8 同源蛋白存在於果蠅 秀麗隱桿線蟲與及所有哺乳類 9 不過 位處細胞膜間的類澱粉蛋白並不高度保守於物種間 亦與前類澱粉蛋白質的生物功能沒有明顯關係 9 某些基因突變如果發生在前類澱粉蛋白質的重要位置 包括但不限於發生在類澱粉蛋白序列組中 就會增加患上遺傳性阿兹海默症的機會 10 11 12 例如一些發生在類澱粉蛋白序列外面的基因突變就被認為導致類澱粉蛋白增長 13 亦有些基因突變 例如是A673T 就被認為能減低患上阿兹海默症的機會 這個突變位於 beta secretase cleavage site 理論上能經由減低beta C Terminus fragment 而抑壓類澱粉蛋白的生成 證據顯示於試管內能減低40 類澱粉蛋白生成 14 參閱 编辑彈震症 英语 Shell shock shell shock 外部連結 编辑 Hynes TR Randal M Kennedy LA Eigenbrot C Kossiakoff AA X ray crystal structure of the protease inhibitor domain of Alzheimer s amyloid beta protein precursor Biochemistry Oct 1990 29 43 10018 22 PMID 2125487 doi 10 1021 bi00495a002 Priller C Bauer T Mitteregger G Krebs B Kretzschmar HA Herms J Synapse formation and function is modulated by the amyloid precursor protein The Journal of Neuroscience Jul 2006 26 27 7212 21 PMID 16822978 doi 10 1523 JNEUROSCI 1450 06 2006 Turner PR O Connor K Tate WP Abraham WC Roles of amyloid precursor protein and its fragments in regulating neural activity plasticity and memory Progress in Neurobiology May 2003 70 1 1 32 PMID 12927332 doi 10 1016 S0301 0082 03 00089 3 Duce JA Tsatsanis A Cater MA James SA Robb E Wikhe K Leong SL Perez K Johanssen T Greenough MA Cho HH Galatis D Moir RD Masters CL McLean C Tanzi RE Cappai R Barnham KJ Ciccotosto GD Rogers JT Bush AI Iron export ferroxidase activity of b amyloid precursor protein is inhibited by zinc in Alzheimer s disease Cell Sep 2010 142 6 857 67 PMC 2943017 PMID 20817278 doi 10 1016 j cell 2010 08 014 Tharp WG Sarkar IN Origins of amyloid b BMC Genomics April 2013 14 1 290 PMID 23627794 doi 10 1186 1471 2164 14 290 Yoshikai S Sasaki H Doh ura K Furuya H Sakaki Y Genomic organization of the human amyloid beta protein precursor gene Gene Mar 1990 87 2 257 63 PMID 2110105 doi 10 1016 0378 1119 90 90310 N Lamb BT Sisodia SS Lawler AM Slunt HH Kitt CA Kearns WG Pearson PL Price DL Gearhart JD Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice corrected Nature Genetics Sep 1993 5 1 22 30 PMID 8220418 doi 10 1038 ng0993 22 Matsui T Ingelsson M Fukumoto H Ramasamy K Kowa H Frosch MP Irizarry MC Hyman BT Expression of APP pathway mRNAs and proteins in Alzheimer s disease Brain Research Aug 2007 1161 116 23 PMID 17586478 doi 10 1016 j brainres 2007 05 050 9 0 9 1 Zheng H Koo EH The amyloid precursor protein beyond amyloid Molecular Neurodegeneration 2006 1 1 5 PMC 1538601 PMID 16930452 doi 10 1186 1750 1326 1 5 Goate A Chartier Harlin MC Mullan M Brown J Crawford F Fidani L Giuffra L Haynes A Irving N James L Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer s disease Nature Feb 1991 349 6311 704 6 PMID 1671712 doi 10 1038 349704a0 Murrell J Farlow M Ghetti B Benson MD A mutation in the amyloid precursor protein associated with hereditary Alzheimer s disease Science Oct 1991 254 5028 97 9 PMID 1925564 doi 10 1126 science 1925564 Chartier Harlin MC Crawford F Houlden H Warren A Hughes D Fidani L Goate A Rossor M Roques P Hardy J Early onset Alzheimer s disease caused by mutations at codon 717 of the beta amyloid precursor protein gene Nature Oct 1991 353 6347 844 6 PMID 1944558 doi 10 1038 353844a0 Citron M Oltersdorf T Haass C McConlogue L Hung AY Seubert P Vigo Pelfrey C Lieberburg I Selkoe DJ Mutation of the beta amyloid precursor protein in familial Alzheimer s disease increases beta protein production Nature Dec 1992 360 6405 672 4 PMID 1465129 doi 10 1038 360672a0 Jonsson T Atwal JK Steinberg S Snaedal J Jonsson PV Bjornsson S Stefansson H Sulem P Gudbjartsson D Maloney J Hoyte K Gustafson A Liu Y Lu Y Bhangale T Graham RR Huttenlocher J Bjornsdottir G Andreassen OA Jonsson EG Palotie A Behrens TW Magnusson OT Kong A Thorsteinsdottir U Watts RJ Stefansson K A mutation in APP protects against Alzheimer s disease and age related cognitive decline Nature Aug 2012 488 7409 96 9 PMID 22801501 doi 10 1038 nature11283 原始内容存档于2020 11 12 使用 archiveurl 需要含有 url 帮助 简明摘要 The New York Times 使用 accessdate 需要含有 url 帮助 取自 https zh wikipedia org w index php title 前類澱粉蛋白質 amp oldid 68836808, 维基百科，wiki，书籍，书籍，图书馆，

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