前类淀粉蛋白质

Amyloid beta (A4) precursor protein
Amyloid beta (A4) precursor protein
	PDB rendering based on 1aap
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB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 organization;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	351
Ensembl	ENSG00000142192
UniProt	P05067
mRNA序列	NM_000484
蛋白序列	NP_000475
基因位置	Chr 21:; 25.88 – 26.17 Mb
PubMed查询	[1]
	查; 论; 编;

前类淀粉蛋白质 (英语: Amyloid precursor protein, APP) 是一个细胞膜内嵌蛋白，在很多组织都能找到，但主要集中在神经元的突触。一般认为前类淀粉蛋白质能够调控突触的形成,^[2] 神经可塑性^[3]及排出铁原子^[4]，但其主要功能仍然未明。

类淀粉蛋白的生成被广泛认为是由前类淀粉蛋白质经蛋白酶解所产生。类淀粉蛋白是一个由37 至49颗氨基酸所组成的不可溶的纤维性蛋白质，其沉积之后形成的类淀粉蛋白斑能够在阿兹海默症病人的大脑中被找到，并被认为是很多神经性疾病的病因。

基因学

前类淀粉蛋白质表达于很多不同的物种而且高度保守^[5]。其基因序列位于人类第21号染色体，拥有290,000个碱基对而组成18个外显子。^[6]^[7] 在人体中，基于选择性剪接，前类淀粉蛋白质有几个等位蛋白（英语：Protein isoform），长度由365至770个氨基酸不等，其中一些等位蛋白主要于神经元表达。等位蛋白间比例的改变被认为与阿兹海默症有关。^[8] 同源蛋白存在于果蝇，秀丽隐杆线虫与及所有哺乳类。^[9] 不过，位处细胞膜间的类淀粉蛋白并不高度保守于物种间，亦与前类淀粉蛋白质的生物功能没有明显关系。^[9]

某些基因突变如果发生在前类淀粉蛋白质的重要位置，包括但不限于发生在类淀粉蛋白序列组中，就会增加患上遗传性阿兹海默症的机会。^[10]^[11]^[12]例如一些发生在类淀粉蛋白序列外面的基因突变就被认为导致类淀粉蛋白增长。^[13]

亦有些基因突变，例如是A673T，就被认为能减低患上阿兹海默症的机会。这个突变位于 beta secretase cleavage site，理论上能经由减低beta C-Terminus fragment 而抑压类淀粉蛋白的生成。证据显示于试管内能减低40% 类淀粉蛋白生成。^[14]

参阅

弹震症（英语：Shell shock）(shell shock)

外部链接

^ 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 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.
^ Tharp WG, Sarkar IN. Origins of amyloid-β. 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, 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 [2016-02-05]. PMID 22801501. doi:10.1038/nature11283. （原始内容存档于2020-11-12）. 简明摘要 – The New York Times.

[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.

[Priller-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.

[Turner-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.

[Duce-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.

[Sarkar-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.

[Yoshikai-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.

[Lamb-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.

[Matsui-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.

[Zheng-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.

[Goate-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.

[Murrell-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.

[Chartier-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.

[Citron-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.

[Jonsson_2012-14] 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 [2016-02-05]. PMID 22801501. doi:10.1038/nature11283. （原始内容存档于2020-11-12）. 简明摘要 – The New York Times.

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