前類澱粉蛋白質

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] 神經可塑性^[3]及排出鐵原子^[4]，但其主要功能仍然未明。

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茲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。

Amyloid beta (A4) precursor protein
PDB rendering based on 1aap[1]
有效結構 PDB 直系同源檢索：PDBe, RCSB PDB查詢代碼列表 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
標識
代號	APP; AAA; ABETA; ABPP; AD1; APPI; CTFgamma; CVAP; PN-II; PN2
擴展標識	遺傳學：104760 鼠基因：88059 同源基因：56379 ChEMBL: 2487 GeneCards: APP Gene
基因本體論描述 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 細胞成分 · 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 生物過程 · 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表達模式
更多表達數據
直系同源體
物種	人類	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查詢	[1]	[2]
閱 論 編

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（英語：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茲海默症有關。^[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茲海默症的機會。^[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茲海默症的機會。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（英語：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. 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 [2016-02-05]. PMID 22801501. doi:10.1038/nature11283. （原始內容存檔於2020-11-12）. 簡明摘要 – The New York Times.