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The Alzheimer’s disease amyloid β-protein (Aβpeptide; precursor: App, γ-secretase) (42aas) (3-d structure is known from NMR spectroscopy (1Z0Q_A; Jang et al., 2007; Zheng et al., 2008)).  This peptide is derived from the amyloid βA4 protein isoform f (NP_001129602)) which forms variable oligomeric toxic pores leading to cytosolic calcium elevation and Alzheimer's disease (Demuro et al., 2011). The monomer of Ass1-42 normally activates type-1 insulin-like growth factor receptors and enhances glucose uptake in neurons and peripheral cells by promoting the translocation of the Glut3 glucose transporter from the cytosol to the plasma membrane (Giuffrida et al. 2015). At nanomolar concentrations, APPsα is an allosteric activator of α7-nAcChR (see TC family 1.A.9), mediated by the C-terminal 16 aas (CTα16) (Korte 2019).

Accession Number:P05067
Protein Name:Amyloid beta A4 protein
Molecular Weight:86943.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Membrane1 / Single-pass type I membrane protein2
Substrate ions

Cross database links:

RefSeq: NP_000475.1    NP_001129601.1    NP_001129602.1    NP_958816.1    NP_958817.1   
Entrez Gene ID: 351   
Pfam: PF02177    PF10515    PF03494    PF00014   
OMIM: 104300  phenotype
104760  gene+phenotype
605714  phenotype
KEGG: hsa:351   

Gene Ontology

GO:0030424 C:axon
GO:0009986 C:cell surface
GO:0005905 C:coated pit
GO:0043198 C:dendritic shaft
GO:0043197 C:dendritic spine
GO:0005576 C:extracellular region
GO:0005794 C:Golgi apparatus
GO:0005887 C:integral to plasma membrane
GO:0031093 C:platelet alpha granule lumen
GO:0033130 F:acetylcholine receptor binding
GO:0003677 F:DNA binding
GO:0008201 F:heparin binding
GO:0042802 F:identical protein binding
GO:0046872 F:metal ion binding
GO:0004867 F:serine-type endopeptidase inhibitor activity
GO:0008344 P:adult locomotory behavior
GO:0008088 P:axon cargo transport
GO:0016199 P:axon midline choice point recognition
GO:0007155 P:cell adhesion
GO:0006878 P:cellular copper ion homeostasis
GO:0048669 P:collateral sprouting in the absence of injury
GO:0016358 P:dendrite development
GO:0006897 P:endocytosis
GO:0030198 P:extracellular matrix organization
GO:0000085 P:G2 phase of mitotic cell cycle
GO:0035235 P:ionotropic glutamate receptor signaling pat...
GO:0007617 P:mating behavior
GO:0006378 P:mRNA polyadenylation
GO:0051402 P:neuron apoptosis
GO:0016322 P:neuron remodeling
GO:0007219 P:Notch signaling pathway
GO:0045931 P:positive regulation of mitotic cell cycle
GO:0006468 P:protein amino acid phosphorylation
GO:0007176 P:regulation of epidermal growth factor recep...
GO:0040014 P:regulation of multicellular organism growth
GO:0050803 P:regulation of synapse structure and activity
GO:0006417 P:regulation of translation
GO:0008542 P:visual learning

References (129)

[1] “The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor.”  Kang   2881207
[2] “A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors.”  Ponte   2893289
[3] “The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons.”  Lemaire   2783775
[4] “Genomic organization of the human amyloid beta-protein precursor gene.”  Yoshikai   2110105
[5] “”  Yoshikai   1908403
[6] “Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells.”  Koenig   1587857
[7] “A novel method for making nested deletions and its application for sequencing of a 300 kb region of human APP locus.”  Hattori   9108164
[8] “Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639.”  Tang   12859342
[9] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota   14702039
[10] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project   15489334
[11] “A cDNA specifying the human amyloid beta precursor protein (ABPP) encodes a 95-kDa polypeptide.”  Schon   3140222
[12] “Characterization of the 5'-end region and the first two exons of the beta-protein precursor gene.”  La Fauci   2538123
[13] “Purification of protease nexin II from human fibroblasts.”  van Nostrand   3597385
[14] “Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.”  Gevaert   12665801
[15] “Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.”  Tanzi   2893290
[16] “Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity.”  Kitaguchi   2893291
[17] “Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex.”  Zain   2893379
[18] “Regulation of amyloid protein precursor (APP) binding to collagen and mapping of the binding sites on APP and collagen type I.”  Beher   8576160
[19] “A system for studying the effect(s) of familial Alzheimer disease mutations on the processing of the beta-amyloid peptide precursor.”  Denman   8476439
[20] “Alzheimer's disease amyloid peptide is encoded by two exons and shows similarity to soybean trypsin inhibitor.”  Johnstone   2675837
[21] “Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease.”  Wakutani   15201367
[22] “Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease.”  Roher   8248178
[23] “Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids.”  Seubert   1406936
[24] “The amino acid sequence of neuritic plaque amyloid from a familial Alzheimer's disease patient.”  Wisniewski   8109908
[25] “Characterization of beta-amyloid peptide from human cerebrospinal fluid.”  Vigo-Pelfrey   8229004
[26] “Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels.”  Pardridge   3312495
[27] “Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease.”  Goldgaber   3810169
[28] “Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus.”  Tanzi   2949367
[29] “BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome.”  Sun   16816112
[30] “A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein.”  de Sauvage   2569763
[31] “Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides.”  Robakis   3035574
[32] “The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene.”  Pangalos   7737970
[33] “Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions.”  Walter   9168929
[34] “Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins.”  Kontush   11775062
[35] “The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II.”  Oltersdorf   2506449
[36] “Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease amyloid protein precursor.”  Kido   1969731
[37] “A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease.”  Bush   8344894
[38] “Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o).”  Nishimoto   8446172
[39] “The beta A4 amyloid precursor protein binding to copper.”  Hesse   7913895
[40] “A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth.”  Small   8158260
[41] “Familial Alzheimer's disease-linked mutations at Val717 of amyloid precursor protein are specific for the increased secretion of A beta 42(43).”  Maruyama   8886002
[42] “APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein.”  Chow   8626687
[43] “The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein.”  Borg   8887653
[44] “Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein.”  Guenette   8855266
[45] “Expression and analysis of heparin-binding regions of the amyloid precursor protein of Alzheimer's disease.”  Mok   9357988
[46] “An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease.”  Yan   9338779
[47] “PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein.”  Zheng   9843960
[48] “Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease.”  Liu   10413512
[49] “Methionine residue 35 is important in amyloid beta-peptide-associated free radical oxidative stress.”  Varadarajan   10535332
[50] “Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein.”  Tomita   9890987
[51] “Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42.”  Perez   10383380
[52] “Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein.”  Ruiz   10461923
[53] “Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides.”  Tokuda   10816430
[54] “Beta-amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology.”  Wang   10681545
[55] “Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor.”  Passer   12214090
[56] “Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages.”  Yazawa   11689470
[57] “Beta-amyloid peptide-induced apoptosis regulated by a novel protein containing a G protein activation module.”  Kajkowski   11278849
[58] “Alzheimer's disease amyloid-beta binds copper and zinc to generate an allosterically ordered structure containing superoxide dismutase-like subunits.”  Curtain   11274207
[59] “Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease.”  Scheuermann   11438549
[60] “The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner.”  Kimberly   11544248
[61] “Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and modulates its physiological function.”  Ohsawa   11238726
[62] “Direct interaction of soluble human recombinant tau protein with Abeta 1-42 results in tau aggregation and hyperphosphorylation by tau protein kinase II.”  Rank   11943163
[63] “Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP).”  Scheinfeld   11724784
[64] “Contrasting species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein.”  White   11784781
[65] “The galvanization of beta-amyloid in Alzheimer's disease.”  Bush   12032279
[66] “Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its processing in an isoform-specific manner.”  Ghersi   15347684
[67] “Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein.”  Suzuki   8131745
[68] “Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations.”  Walter   8999878
[69] “Copper-binding amyloid precursor protein undergoes a site-specific fragmentation in the reduction of hydrogen peroxide.”  Multhaup   9585534
[70] “Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation.”  Gervais   10319819
[71] “Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation.”  Ando   10341243
[72] “Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2.”  Walter   10806211
[73] “A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.”  Lu   10742146
[74] “Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid.”  Ando   11517218
[75] “Phosphorylation of thr(668) in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress-activated protein kinase 1b (Jun N-terminal kinase-3).”  Standen   11146006
[76] “A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing.”  Weidemann   11851430
[77] “Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc.”  Tarr   11877420
[78] “Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.”  Liu   16335952
[79] “Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.”  Dyrks   2900137
[80] “A cell biological perspective on Alzheimer's disease.”  Annaert   12142279
[81] “Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.”  Rikova   18083107
[82] “Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells.”  Nakaya   18468999
[83] “BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2.”  Matsuda   19366692
[84] “An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells.”  Heibeck   19534553
[85] “APP binds DR6 to trigger axon pruning and neuron death via distinct caspases.”  Nikolaev   19225519
[86] “RAGE-mediated signaling contributes to intraneuronal transport of amyloid-{beta} and neuronal dysfunction.”  Takuma   19901339
[87] “X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor.”  Hynes   2125487
[88] “Sequential NMR resonance assignment and structure determination of the Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor protein.”  Heald   1718421
[89] “Solution structure of residues 1-28 of the amyloid beta-peptide.”  Talafous   7516706
[90] “Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease.”  Sticht   7588758
[91] “Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment.”  Kohno   8973180
[92] “Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities.”  Scheidig   9300481
[93] “Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?”  Coles   9693002
[94] “Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein.”  Rossjohn   10201399
[95] “Substitutions at codon 22 of Alzheimer's Abeta peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells.”  Miravalle   10821838
[96] “The Alzheimer's peptide a beta adopts a collapsed coil structure in water.”  Zhang   10940221
[97] “Solution structures in aqueous SDS micelles of two amyloid beta peptides of Abeta(1-28) mutated at the alpha-secretase cleavage site.”  Poulsen   10940222
[98] “The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain.”  Wang   15304215
[99] “Framing beta-amyloid.”  Hardy   1363811
[100] “Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type.”  Levy   2111584
[101] “Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.”  Goate   1671712
[102] “The 717Val-->Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups.”  Yoshioka   1908231
[103] “Mis-sense mutation Val->Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease.”  Naruse   1678058
[104] “Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.”  Chartier-Harlin   1944558
[105] “A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.”  Murrell   1925564
[106] “Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region.”  Kamino   1415269
[107] “Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene.”  Hendriks   1303239
[108] “A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid.”  Mullan   1302033
[109] “Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia.”  Jones   1307241
[110] “More missense in amyloid gene.”  Carter   1303275
[111] “Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease with APP717 mutations.”  Liepnieks   8267572
[112] “Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late-onset Alzheimer's disease.”  Peacock   8154870
[113] “Clinical characteristics in a kindred with early-onset Alzheimer's disease and their linkage to a G-->T change at position 2149 of the amyloid precursor protein gene.”  Farlow   8290042
[114] “A mutation in codon 717 of the amyloid precursor protein gene in an Australian family with Alzheimer's disease.”  Brooks   8577393
[115] “A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43).”  Eckman   9328472
[116] “Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation.”  Cras   9754958
[117] “Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP) maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for probable early-onset Alzheimer's disease.”  Ancolio   10097173
[118] “High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.”  Finckh   10631141
[119] “Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis.”  Kwok   10665499
[120] “Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene.”  Murrell   10867787
[121] “Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site mutation points to an essential role for N-truncated A beta(42) in Alzheimer's disease.”  Kumar-Singh   11063718
[122] “Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy.”  Grabowski   11409420
[123] “In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease.”  Walsh   11311152
[124] “The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation.”  Nilsberth   11528419
[125] “An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala).”  Pasalar   12034808
[126] “Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation.”  Greenberg   12654973
[127] “A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene.”  Rossi   15365148
[128] “A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy.”  Obici   16178030
[129] “An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.”  Edwards-Lee   15668448
1AAP   1AMB   1AMC   1AML   1BA4   1BA6   1BJB   1BJC   1BRC   1CA0   [...more]

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