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P05067

- A4_HUMAN

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Protein
Amyloid beta A4 protein
Gene
APP, A4, AD1

Gene:

APP, A4, AD1
Organism
Homo sapiens (Human)
Status
Reviewed - - Experimental evidence at protein leveli

UniProt

P05067 - A4_HUMAN

Protein:

Amyloid beta A4 protein
Protein Existence: Experimental evidence at protein level

Functioni

Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity By similarity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.5 Publications
Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu2+ and Fe3+ to Cu+ and Fe2+, respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.5 Publications
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain By similarity.5 Publications
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.5 Publications
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Sitei1441Required for Cu(2+) reduction
Metal bindingi1471Copper 1
Metal bindingi1511Copper 1
Metal bindingi1681Copper 1
Sitei301 – 3022Reactive bond
Sitei671 – 6722Cleavage; by beta-secretase
Sitei672 – 6732Cleavage; by caspase-6; when associated with variant 670-N-L-671
Metal bindingi6771Copper or zinc 2
Metal bindingi6811Copper or zinc 2 Inferred
Metal bindingi6841Copper or zinc 2
Metal bindingi6851Copper or zinc 2
Sitei687 – 6882Cleavage; by alpha-secretase
Sitei690 – 6912Cleavage; by theta-secretase
Sitei7041Implicated in free radical propagation By similarity
Sitei7061Susceptible to oxidation
Sitei711 – 7122Cleavage; by gamma-secretase; site 1
Sitei713 – 7142Cleavage; by gamma-secretase; site 2
Sitei720 – 7212Cleavage; by gamma-secretase; site 3
Sitei739 – 7402Cleavage; by caspase-6, caspase-8 or caspase-9

GO - Molecular functioni

  1. DNA bindingInferred from sequence or structural similarityi Source: UniProtKB
  2. heparin bindingInferred from electronic annotationi Source: UniProtKB-KW
  3. peptidase activator activityInferred from electronic annotationi Source: Ensembl
  4. serine-type endopeptidase inhibitor activityInferred from direct assayi PubMed 10652580 Source: UniProtKB
  5. transition metal ion bindingInferred from electronic annotationi Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. DNA bindingInferred from sequence or structural similarityi Source: UniProtKB
  2. heparin bindingInferred from electronic annotationi Source: UniProtKB-KW
  3. peptidase activator activityInferred from electronic annotationi Source: Ensembl
  4. serine-type endopeptidase inhibitor activityInferred from direct assayi PubMed 10652580 Source: UniProtKB
  5. transition metal ion bindingInferred from electronic annotationi Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Apoptosis, Cell adhesion, Endocytosis, Notch signaling pathway

Keywords - Ligandi

Copper, Heparin-binding, Iron, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000142192-MONOMER.
ReactomeiREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SABIO-RKiP05067.

Protein family/group databases

MEROPSiI02.015.
TCDBi1.C.50.1.2. the amyloid -protein peptide (app) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid beta A4 protein
Alternative name(s):
ABPP
APPI
Short name:
APP
Alzheimer disease amyloid protein
Cerebral vascular amyloid peptide
Short name:
CVAP
PreA4
Protease nexin-II
Short name:
PN-II
Cleaved into the following 14 chains:
Soluble APP-alpha
Short name:
S-APP-alpha
Soluble APP-beta
Short name:
S-APP-beta
Alternative name(s):
Beta-APP42
Alternative name(s):
Beta-APP40
Alternative name(s):
Amyloid intracellular domain 59
Short name:
AICD-59
Short name:
AID(59)
Gamma-CTF(59)
Alternative name(s):
Amyloid intracellular domain 57
Short name:
AICD-57
Short name:
AID(57)
Gamma-CTF(57)
Alternative name(s):
Amyloid intracellular domain 50
Short name:
AICD-50
Short name:
AID(50)
Gamma-CTF(50)
Gene namesi
Name:APP
Synonyms:A4, AD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 21

Organism-specific databases

HGNCiHGNC:620. APP.

Subcellular locationi

Membrane; Single-pass type I membrane protein. Membraneclathrin-coated pit
Note: Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Topological domaini18 – 699682Extracellular Reviewed prediction
Transmembranei700 – 72324Helical; Reviewed prediction
Topological domaini724 – 77047Cytoplasmic Reviewed prediction

GO - Cellular componenti

  1. Golgi apparatusInferred from direct assayi PubMed 20427278 Source: UniProtKB
  2. apical part of cellInferred from electronic annotationi Source: Ensembl
  3. axonInferred from sequence or structural similarityi Source: UniProtKB
  4. cell surfaceInferred from direct assayi PubMed 7593229 Source: UniProtKB
  5. ciliary rootletInferred from electronic annotationi Source: Ensembl
  6. coated pitInferred from electronic annotationi Source: UniProtKB-SubCell
  7. cytosolTraceable author statementi Source: Reactome
  8. dendritic shaftInferred from direct assayi PubMed 11988176 Source: MGI
  9. dendritic spineInferred from direct assayi PubMed 11988176 Source: MGI
  10. extracellular vesicular exosomeInferred from direct assayi PubMed 19199708 Source: UniProt
  11. integral component of plasma membraneTraceable author statementi PubMed 10806211 Source: ProtInc
  12. neuromuscular junctionInferred from electronic annotationi Source: Ensembl
  13. perinuclear region of cytoplasmInferred from direct assayi PubMed 20427278 Source: UniProt
  14. platelet alpha granule lumenTraceable author statementi Source: Reactome
  15. receptor complexInferred from direct assayi PubMed 23382219 Source: MGI
  16. spindle midzoneInferred from electronic annotationi Source: Ensembl
  17. synapseInferred from direct assayi PubMed 11988176 Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Coated pit, Membrane

Pathology & Biotechi

Involvement in diseasei

Alzheimer disease 1 (AD1) [MIM:104300]: A familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Natural varianti670 – 6712KM → NL in AD1.
VAR_000015
Natural varianti6781D → N in AD1. 1 Publication
VAR_044424
Natural varianti6921A → G in AD1; Flemish mutation; increases the solubility of processed beta-amyloid peptides and increases the stability of peptide oligomers. 3 Publications
VAR_000016
Natural varianti6931E → G in AD1. 2 Publications
VAR_014215
Natural varianti7131A → T in AD1. 2 Publications
VAR_000019
Natural varianti7141T → A in AD1. 1 Publication
VAR_032277
Natural varianti7141T → I in AD1; increased beta-APP42/beta-APP40 ratio. 2 Publications
VAR_014218
Natural varianti7151V → M in AD1; decreased beta-APP40/total APP-beta. 1 Publication
VAR_010108
Natural varianti7161I → V in AD1. 1 Publication
VAR_000020
Natural varianti7171V → F in AD1. 4 Publications
VAR_000023
Natural varianti7171V → G in AD1. 2 Publications
VAR_000022
Natural varianti7171V → I in AD1. 7 Publications
VAR_000021
Natural varianti7171V → L in AD1. 1 Publication
VAR_014219
Natural varianti7231L → P in AD1. 1 Publication
VAR_010109
Cerebral amyloid angiopathy, APP-related (CAA-APP) [MIM:605714]: A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Natural varianti6931E → K in CAA-APP; Italian type.
VAR_014216
Natural varianti6931E → Q in CAA-APP; Dutch type. 1 Publication
VAR_000017
Natural varianti6941D → N in CAA-APP; Iowa type. 2 Publications
VAR_014217
Natural varianti7051L → V in CAA-APP; Italian type. 1 Publication
VAR_032276

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Mutagenesisi99 – 1024KRGR → NQGG: Reduced heparin-binding. 1 Publication
Mutagenesisi1371H → N: Binds copper. Forms dimer. 1 Publication
Mutagenesisi1411M → T: Binds copper. Forms dimer. 1 Publication
Mutagenesisi1441C → S: Binds copper. No dimer formation. No copper reducing activity. 2 Publications
Mutagenesisi147 – 1493HLH → ALA: 50% decrease in copper reducing activity. 3 Publications
Mutagenesisi1471H → A: Some decrease in copper reducing activity. 2 Publications
Mutagenesisi1471H → N: Binds copper. Forms dimer. 2 Publications
Mutagenesisi1471H → Y: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications
Mutagenesisi1511H → K: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications
Mutagenesisi1511H → N: Binds copper. Forms dimer. 2 Publications
Mutagenesisi1981S → A: Greatly reduced casein kinase phosphorylation. 2 Publications
Mutagenesisi2061S → A: Reduced casein kinase phosphorylation. 2 Publications
Mutagenesisi4991R → A: Reduced affinity for heparin; when associated with A-503. 1 Publication
Mutagenesisi5031K → A: Reduced affinity for heparin; when associated with A-499. 1 Publication
Mutagenesisi6561S → A: Abolishes chondroitin sulfate binding in L-APP733 isoform. 1 Publication
Mutagenesisi6761R → G: 60-70% zinc-induced beta-APP (28) peptide aggregation. 1 Publication
Mutagenesisi6811Y → F: 60-70% zinc-induced beta-APP (28) peptide aggregation. 1 Publication
Mutagenesisi6841H → R: Only 23% zinc-induced beta-APP (28) peptide aggregation. 1 Publication
Mutagenesisi7041G → V: Reduced protein oxidation. No hippocampal neuron toxicity.
Mutagenesisi7061M → L: Reduced lipid peroxidation inhibition. 2 Publications
Mutagenesisi7061M → V: No free radical production. No hippocampal neuron toxicity. 2 Publications
Mutagenesisi7171V → C or S: Unchanged beta-APP42/total APP-beta ratio. 2 Publications
Mutagenesisi7171V → F, G or I: Increased beta-APP42/beta-APP40 ratio. 2 Publications
Mutagenesisi7171V → K: Decreased beta-APP42/total APP-beta ratio. 2 Publications
Mutagenesisi7171V → M: Increased beta-APP42/beta-APP40 ratio. No change in apoptosis after caspase cleavage. 2 Publications
Mutagenesisi7281Y → A: No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in beta-APP42 secretion. 3 Publications
Mutagenesisi7391D → A: No cleavage by caspases during apoptosis. 3 Publications
Mutagenesisi7391D → N: No effect on FADD-induced apoptosis. 3 Publications
Mutagenesisi7431T → A: Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension. 4 Publications
Mutagenesisi7431T → E: Reduced NGF-stimulated neurite extension. No effect on APP maturation. 4 Publications
Mutagenesisi7561G → A: APP internalization unchanged. No change in beta-APP42 secretion. 1 Publication
Mutagenesisi7571Y → A: Little APP internalization. Reduced beta-APP42 secretion. 4 Publications
Mutagenesisi7571Y → G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1. 4 Publications
Mutagenesisi7591N → A: No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced beta-APP42 secretion. 2 Publications
Mutagenesisi7601P → A: Little APP internalization. Reduced beta-APP42 secretion. 1 Publication
Mutagenesisi7621Y → A: Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in beta-APP42 secretion. 2 Publications

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

Organism-specific databases

MIMi104300. phenotype.
605714. phenotype.
Orphaneti1020. Early-onset autosomal dominant Alzheimer disease.
324723. Hereditary cerebral hemorrhage with amyloidosis, Arctic type.
100006. Hereditary cerebral hemorrhage with amyloidosis, Dutch type.
324718. Hereditary cerebral hemorrhage with amyloidosis, Flemish type.
324708. Hereditary cerebral hemorrhage with amyloidosis, Iowa type.
324713. Hereditary cerebral hemorrhage with amyloidosis, Italian type.
324703. Hereditary cerebral hemorrhage with amyloidosis, Piedmont type.
PharmGKBiPA24910.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Signal peptidei1 – 17172 Publications
Chaini18 – 770753Amyloid beta A4 protein
PRO_0000000088
Chaini18 – 687670Soluble APP-alpha
PRO_0000000089
Chaini18 – 671654Soluble APP-beta
PRO_0000000090
Chaini18 – 286269N-APP
PRO_0000381966
Chaini672 – 77099C99
PRO_0000000091
Chaini672 – 71342Beta-amyloid protein 42
PRO_0000000092
Chaini672 – 71140Beta-amyloid protein 40
PRO_0000000093
Chaini688 – 77083C83
PRO_0000000094
Peptidei688 – 71326P3(42)
PRO_0000000095
Peptidei688 – 71124P3(40)
PRO_0000000096
Chaini691 – 77080C80
PRO_0000384574
Chaini712 – 77059Gamma-secretase C-terminal fragment 59
PRO_0000000097
Chaini714 – 77057Gamma-secretase C-terminal fragment 57
PRO_0000000098
Chaini721 – 77050Gamma-secretase C-terminal fragment 50 By similarity
PRO_0000000099
Chaini740 – 77031C31
PRO_0000000100

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Disulfide bondi38 ↔ 624 Publications
Disulfide bondi73 ↔ 1174 Publications
Disulfide bondi98 ↔ 1054 Publications
Disulfide bondi133 ↔ 1874 Publications
Disulfide bondi144 ↔ 1744 Publications
Disulfide bondi158 ↔ 1864 Publications
Modified residuei1981Phosphoserine; by CK21 Publication
Modified residuei2061Phosphoserine; by CK11 Publication
Disulfide bondi291 ↔ 3414 Publications
Disulfide bondi300 ↔ 3244 Publications
Disulfide bondi316 ↔ 3374 Publications
Glycosylationi5421N-linked (GlcNAc...)1 Publication
Glycosylationi5711N-linked (GlcNAc...) Inferred
Glycosylationi6141O-linked (GalNAc...)1 Publication
Glycosylationi6231O-linked (GalNAc...)1 Publication
Glycosylationi6281O-linked (GalNAc...)1 Publication
Glycosylationi6331O-linked (GalNAc...)1 Publication
Glycosylationi6511O-linked (GalNAc...)1 Publication
Glycosylationi6521O-linked (GalNAc...)1 Publication
Glycosylationi6561O-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms1 Publication
Glycosylationi6591O-linked (GalNAc...)
Glycosylationi6631O-linked (GalNAc...) Inferred
Glycosylationi6671O-linked (GalNAc...) Inferred
Glycosylationi6791O-linked (GalNAc...)1 Publication
Glycosylationi6971O-linked (GalNAc...)1 Publication
Modified residuei7291Phosphothreonine By similarity
Modified residuei7301Phosphoserine; by APP-kinase I By similarity
Modified residuei7431Phosphothreonine; by CDK5 and MAPK102 Publications
Modified residuei7571Phosphotyrosine; alternate1 Publication
Modified residuei7571Phosphotyrosine; by ABL1; alternate By similarity

Post-translational modificationi

Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid beta proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many other minor beta-amyloid peptides, beta-amyloid 1-X peptides, are found in cerebral spinal fluid (CSF) including the beta-amyloid X-15 peptides, produced from the cleavage by alpha-secretase and all terminatiing at Gln-686.
Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of beta-amyloid peptides.7 Publications
N- and O-glycosylated. O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short beta-amyloid peptides (beta-amyloid 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on beta-amyloid 38, beta-amyloid 40 nor on beta-amyloid 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate.2 Publications
Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin.7 Publications
Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu+ complex in the presence of hydrogen peroxide results in an increased production of beta-amyloid-containing peptides.
Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).7 Publications
Beta-amyloid peptides are degraded by IDE.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Proteoglycan

Proteomic databases

PaxDbiP05067.
PRIDEiP05067.

2D gel databases

SWISS-2DPAGEiP05067.

PTM databases

PhosphoSiteiP05067.
UniCarbKBiP05067.

Miscellaneous databases

PMAP-CutDBiP05067.

Expressioni

Tissue specificityi

Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra-striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non-neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes.2 Publications

Inductioni

Increased levels during neuronal differentiation.

Gene expression databases

ArrayExpressiP05067.
BgeeiP05067.
GenevestigatoriP05067.

Organism-specific databases

HPAiCAB000157.
HPA001462.

Interactioni

Subunit structurei

Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 By similarity. Binding to DAB1 inhibits its serine phosphorylation By similarity. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, FPRL1, APPBP1, IB1, KNS2 (via its TPR domains) By similarity, APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains By similarity. Associates with microtubules in the presence of ATP and in a kinesin-dependent manner By similarity. Interacts, through a C-terminal domain, with GNAO1. Amyloid beta-42 binds CHRNA7 in hippocampal neurons. Beta-amyloid associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER By similarity. Interacts with ANKS1B and TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; this is promoted by heparin binding. Beta-amyloid protein 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. Interacts with SORL1.27 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself79EBI-77613,EBI-77613
Q306T33EBI-77613,EBI-8294101From a different organism.
AGRNP316963EBI-2431589,EBI-457650From a different organism.
APBA1Q024103EBI-77613,EBI-368690
APBB1O002135EBI-77613,EBI-81694
APBB2Q928702EBI-77613,EBI-79277
APLP1P516932EBI-302641,EBI-74648
APLP2Q064812EBI-302641,EBI-79306
APOA1P026475EBI-77613,EBI-701692
BLMHQ138672EBI-302641,EBI-718504
COL18A1P390602EBI-821758,EBI-2566375
CTSDP073392EBI-77613,EBI-2115097
FLOT1O759555EBI-77613,EBI-603643
FOSP011003EBI-77613,EBI-852851
GPR3P460892EBI-302641,EBI-3909653
HOMER3Q9NSC53EBI-302661,EBI-748420
HSD17B10Q997144EBI-77613,EBI-79964
ITM2AO437363EBI-302641,EBI-2431769
JUNP054122EBI-77613,EBI-852823
MAPTP106369EBI-77613,EBI-366182
MED12Q930742EBI-77613,EBI-394357
MT-ND3P038972EBI-821758,EBI-1246249
NF1P213593EBI-77613,EBI-1172917
NGFRP081382EBI-77613,EBI-1387782
NgfrP071742EBI-2431589,EBI-1038810From a different organism.
PCBD1P614572EBI-77613,EBI-740475
PDIA3P301013EBI-77613,EBI-979862
PIN1Q135262EBI-302641,EBI-714158
PRNPP041563EBI-77613,EBI-977302
PSEN1P497686EBI-77613,EBI-297277
SHC1P293535EBI-77613,EBI-78835
SHC3Q925292EBI-77613,EBI-79084
SLC40A1Q9NP594EBI-77613,EBI-725153
Slc5a7Q8BGY92EBI-77613,EBI-2010752From a different organism.
SPON1Q9HCB63EBI-302641,EBI-2431846
TGFB1P011372EBI-77613,EBI-779636
TGFB2P618126EBI-77613,EBI-779581
TNFRSF21O755093EBI-77613,EBI-2313231
TP53BP2Q136253EBI-77613,EBI-77642

Protein-protein interaction databases

BioGridi106848. 1970 interactions.
DIPiDIP-574N.
IntActiP05067. 110 interactions.
MINTiMINT-150767.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Beta strandi33 – 353
Beta strandi43 – 453
Turni47 – 493
Beta strandi52 – 543
Helixi66 – 7611
Beta strandi82 – 876
Beta strandi92 – 943
Beta strandi97 – 993
Helixi100 – 1023
Beta strandi103 – 1064
Beta strandi110 – 1123
Beta strandi115 – 1195
Beta strandi134 – 1396
Helixi147 – 16014
Beta strandi163 – 17412
Turni175 – 1773
Beta strandi178 – 18811
Helixi288 – 2925
Beta strandi299 – 3013
Beta strandi304 – 3107
Turni311 – 3144
Beta strandi315 – 3217
Beta strandi323 – 3253
Beta strandi331 – 3333
Helixi334 – 3418
Helixi374 – 3807
Helixi389 – 41830
Beta strandi421 – 4233
Helixi425 – 48056
Beta strandi482 – 4843
Helixi487 – 51832
Helixi520 – 54627
Helixi547 – 5504
Helixi552 – 56615
Helixi673 – 6753
Beta strandi679 – 6824
Beta strandi683 – 6853
Beta strandi688 – 6914
Helixi695 – 6973
Beta strandi698 – 7003
Beta strandi702 – 7054
Beta strandi707 – 7126
Helixi744 – 75411
Beta strandi755 – 7584
Beta strandi763 – 7653

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AAPX-ray1.50A/B287-344[»]
1AMBNMR-A672-699[»]
1AMCNMR-A672-699[»]
1AMLNMR-A672-711[»]
1BA4NMR-A672-711[»]
1BA6NMR-A672-711[»]
1BJBNMR-A672-699[»]
1BJCNMR-A672-699[»]
1BRCX-ray2.50I287-342[»]
1CA0X-ray2.10D/I289-342[»]
1HZ3NMR-A681-706[»]
1IYTNMR-A672-713[»]
1MWPX-ray1.80A28-123[»]
1OWTNMR-A124-189[»]
1QCMNMR-A696-706[»]
1QWPNMR-A696-706[»]
1QXCNMR-A696-706[»]
1QYTNMR-A696-706[»]
1TAWX-ray1.80B287-344[»]
1TKNNMR-A460-569[»]
1UO7model-A672-713[»]
1UO8model-A672-713[»]
1UOAmodel-A672-713[»]
1UOImodel-A672-713[»]
1X11X-ray2.50C/D754-766[»]
1Z0QNMR-A672-713[»]
1ZE7NMR-A672-687[»]
1ZE9NMR-A672-687[»]
1ZJDX-ray2.60B289-344[»]
2BEGNMR-A/B/C/D/E672-713[»]
2BOMmodel-A/B681-713[»]
2BP4NMR-A672-687[»]
2FJZX-ray1.61A133-189[»]
2FK1X-ray1.60A133-189[»]
2FK2X-ray1.65A133-189[»]
2FK3X-ray2.40A/B/C/D/E/F/G/H133-189[»]
2FKLX-ray2.50A/B124-189[»]
2FMAX-ray0.85A133-189[»]
2G47X-ray2.10C/D672-711[»]
2IPUX-ray1.65P/Q672-679[»]
2LFMNMR-A672-711[»]
2LLMNMR-A686-726[»]
2LMNNMR-A/B/C/D/E/F/G/H/I/J/K/L672-711[»]
2LMONMR-A/B/C/D/E/F/G/H/I/J/K/L672-711[»]
2LMPNMR-A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R672-711[»]
2LMQNMR-A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R672-711[»]
2LNQNMR-A/B/C/D/E/F/G/H672-711[»]
2LOHNMR-A/B686-726[»]
2LP1NMR-A671-770[»]
2LZ3NMR-A/B699-726[»]
2LZ4NMR-A/B699-726[»]
2M4JNMR-A/B/C/D/E/F/G/H/I672-711[»]
2M9RNMR-A672-711[»]
2M9SNMR-A672-711[»]
2OTKNMR-C672-711[»]
2R0WX-ray2.50Q672-679[»]
2WK3X-ray2.59C/D672-713[»]
2Y29X-ray2.30A687-692[»]
2Y2AX-ray1.91A687-692[»]
2Y3JX-ray1.99A/B/C/D/E/F/G/H701-706[»]
2Y3KX-ray1.90A/B/C/D/E/F/G/H706-713[»]
2Y3LX-ray2.10A/B/C/G706-713[»]
3AYUX-ray2.00B586-595[»]
3DXCX-ray2.10B/D739-770[»]
3DXDX-ray2.20B/D739-770[»]
3DXEX-ray2.00B/D739-770[»]
3GCIX-ray2.04P707-713[»]
3IFLX-ray1.50P672-678[»]
3IFNX-ray1.50P672-711[»]
3IFOX-ray2.15P/Q672-678[»]
3IFPX-ray2.95P/Q/R/S672-678[»]
3JTIX-ray1.80B699-706[»]
3KTMX-ray2.70A/B/C/D/E/F/G/H18-190[»]
3L33X-ray2.48E/F/G/H290-341[»]
3L81X-ray1.60B761-767[»]
3MOQX-ray2.05A/B/C/D689-712[»]
3MXCX-ray2.00L754-762[»]
3MXYX-ray2.30L754-762[»]
3NYJX-ray3.20A365-567[»]
3NYLX-ray2.80A365-570[»]
3OVJX-ray1.80A/B/C/D687-692[»]
3OW9X-ray1.80A/B687-692[»]
3SV1X-ray3.30D/E/F754-767[»]
3U0TX-ray2.50E/F701-711[»]
3UMHX-ray2.00A370-575[»]
3UMIX-ray2.40A370-575[»]
3UMKX-ray2.60A370-575[»]
4HIXX-ray2.20A672-699[»]
ProteinModelPortaliP05067.
SMRiP05067. Positions 26-192, 287-342, 385-567, 683-728, 741-768.

Miscellaneous databases

EvolutionaryTraceiP05067.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Domaini291 – 34151BPTI/Kunitz inhibitor

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Regioni96 – 11015Heparin-binding
Regioni181 – 1888Zinc-binding
Regioni391 – 42333Heparin-binding
Regioni491 – 52232Heparin-binding
Regioni523 – 54018Collagen-binding
Regioni732 – 75120Interaction with G(o)-alpha

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Motifi724 – 73411Basolateral sorting signal
Motifi759 – 7624NPXY motif; contains endocytosis signal

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Compositional biasi230 – 26031Asp/Glu-rich (acidic)
Compositional biasi274 – 2807Poly-Thr

Domaini

The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.7 Publications
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The NPXY site is also involved in clathrin-mediated endocytosis.7 Publications

Sequence similaritiesi

Belongs to the APP family.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG289770.
HOVERGENiHBG000051.
InParanoidiP05067.
KOiK04520.
OMAiTHAHIVI.
OrthoDBiEOG7RNJZP.
PhylomeDBiP05067.
TreeFamiTF317274.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.230.10. 1 hit.
4.10.410.10. 1 hit.
InterProiIPR008155. Amyloid_glyco.
IPR013803. Amyloid_glyco_Abeta.
IPR011178. Amyloid_glyco_Cu-bd.
IPR024329. Amyloid_glyco_E2_domain.
IPR008154. Amyloid_glyco_extra.
IPR019744. Amyloid_glyco_extracell_CS.
IPR015849. Amyloid_glyco_heparin-bd.
IPR019745. Amyloid_glyco_intracell_CS.
IPR028866. APP.
IPR019543. APP_amyloid_C.
IPR002223. Prot_inh_Kunz-m.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PANTHERiPTHR23103:SF7. PTHR23103:SF7. 1 hit.
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
PF03494. Beta-APP. 1 hit.
PF00014. Kunitz_BPTI. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
PR00759. BASICPTASE.
PR00204. BETAAMYLOID.
SMARTiSM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF57362. SSF57362. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
PS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view]

Sequences (11)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 11 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.

Isoform APP770 (identifier: P05067-1) [UniParc]FASTA

Also known as: PreA4 770

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG    50
KWDSDPSGTK TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR 100
GRKQCKTHPH FVIPYRCLVG EFVSDALLVP DKCKFLHQER MDVCETHLHW 150
HTVAKETCSE KSTNLHDYGM LLPCGIDKFR GVEFVCCPLA EESDNVDSAD 200
AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE EADDDEDDED 250
GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC 300
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL 350
KTTQEPLARD PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA 400
KHRERMSQVM REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER 450
QQLVETHMAR VEAMLNDRRR LALENYITAL QAVPPRPRHV FNMLKKYVRA 500
EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER MNQSLSLLYN 550
VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET 600
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL 650
TTRPGSGLTN IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG 700
AIIGLMVGGV VIATVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS 750
KMQQNGYENP TYKFFEQMQN 770

Note: A major isoform.

Length:770
Mass (Da):86,943
Last modified:November 1, 1991 - v3
Checksum:iA12EE761403740F5
GO
Isoform APP305 (identifier: P05067-2) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     290-305: VCSEQAETGPCRAMIS → KWYKEVHSGQARWLML
     306-770: Missing.

Show »
Length:305
Mass (Da):34,358
Checksum:iD1CCD7237262687A
GO
Isoform L-APP677 (identifier: P05067-3) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-364: Missing.
     637-654: Missing.

Note: The L-isoforms are referred to as appicans.

Show »
Length:677
Mass (Da):76,760
Checksum:i48334D3EEF26990E
GO
Isoform APP695 (identifier: P05067-4) [UniParc]FASTA

Also known as: PreA4 695

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-364: Missing.

Note: A major isoform.

Show »
Length:695
Mass (Da):78,663
Checksum:i4F6EA0139F969D56
GO
Isoform L-APP696 (identifier: P05067-5) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-345: Missing.
     637-654: Missing.

Note: The L-isoforms are referred to as appicans.

Show »
Length:696
Mass (Da):78,866
Checksum:i66DFDFFCFDB75A72
GO
Isoform APP714 (identifier: P05067-6) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-345: Missing.

Show »
Length:714
Mass (Da):80,769
Checksum:i124EA691773DC13B
GO
Isoform L-APP733 (identifier: P05067-7) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     345-345: M → I
     346-364: Missing.
     637-654: Missing.

Note: The L-isoforms are referred to as appicans.

Show »
Length:733
Mass (Da):82,916
Checksum:i44528239D68A53EE
GO
Isoform APP751 (identifier: P05067-8) [UniParc]FASTA

Also known as: PreA4 751

The sequence of this isoform differs from the canonical sequence as follows:
     345-345: M → I
     346-364: Missing.

Note: A major isoform.

Show »
Length:751
Mass (Da):84,819
Checksum:iC987C557C5A3714E
GO
Isoform L-APP752 (identifier: P05067-9) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     637-654: Missing.

Show »
Length:752
Mass (Da):85,040
Checksum:i074CFF767CBED2E0
GO
Isoform APP639 (identifier: P05067-10) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     19-74: Missing.
     289-363: Missing.
     364-364: L → V

Show »
Length:639
Mass (Da):72,553
Checksum:iC4120DEC51A59A95
GO
Isoform 11 (identifier: P05067-11) [UniParc]FASTA

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MLPGLALLLLAAWTARALE → MDQLEDLLVLFINY
     345-364: MSQSLLKTTQEPLARDPVKL → I

Show »
Length:746
Mass (Da):84,521
Checksum:i843411EFBDEFACE3
GO

Sequence conflict

The sequence AAA58727.1 differs from that shown. Reason: Contamination by an Alu repeat.

Mass spectrometryi

Molecular mass is 6461.6 Da from positions 712 - 767. Determined by MALDI.
Molecular mass is 6451.6 Da from positions 714 - 770. Determined by MALDI.
Molecular mass is 6436.8 Da from positions 715 - 769. Determined by MALDI.
Molecular mass is 5752.5 Da from positions 719 - 767. Determined by MALDI.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Natural varianti6651E → D in a patient with late onset Alzheimer disease. 1 Publication
VAR_010107
Natural varianti7131A → V in one chronic schizophrenia patient; unknown pathological significance. 1 Publication
Corresponds to variant rs1800557 [ dbSNP | Ensembl ].
VAR_000018

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Alternative sequencei1 – 1919MLPGL…ARALE → MDQLEDLLVLFINY in isoform 11.
VSP_045446
Alternative sequencei19 – 7456Missing in isoform APP639.
VSP_009116
Alternative sequencei289 – 36375Missing in isoform APP639.
VSP_009117
Alternative sequencei2891E → V in isoform APP695, isoform L-APP696, isoform L-APP677 and isoform APP714.
VSP_000002
Alternative sequencei290 – 36475Missing in isoform APP695 and isoform L-APP677.
VSP_000004
Alternative sequencei290 – 34556Missing in isoform L-APP696 and isoform APP714.
VSP_000003
Alternative sequencei290 – 30516VCSEQ…RAMIS → KWYKEVHSGQARWLML in isoform APP305.
VSP_000005
Alternative sequencei306 – 770465Missing in isoform APP305.
VSP_000006
Alternative sequencei345 – 36420MSQSL…DPVKL → I in isoform 11.
VSP_045447
Alternative sequencei3451M → I in isoform L-APP733 and isoform APP751.
VSP_000007
Alternative sequencei346 – 36419Missing in isoform L-APP733 and isoform APP751.
VSP_000008
Alternative sequencei3641L → V in isoform APP639.
VSP_009118
Alternative sequencei637 – 65418Missing in isoform L-APP677, isoform L-APP696, isoform L-APP733 and isoform L-APP752.
VSP_000009

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Sequence conflicti15 – 162AR → VW in CAA31830. 1 Publication
Sequence conflicti6471D → E in AAA51722. 1 Publication
Sequence conflicti7241Missing in AAB26263. 1 Publication
Sequence conflicti7241Missing in AAB26264. 1 Publication
Sequence conflicti7311I → N in AAB26263. 1 Publication
Sequence conflicti7311I → N in AAB26264. 1 Publication
Sequence conflicti7311I → N in AAB26265. 1 Publication
Sequence conflicti7571Y → S in AAA35540. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00264 mRNA. Translation: CAA68374.1.
X13466
, X13467, X13468, X13469, X13470, X13471, X13472, X13473, X13474, X13475, X13476, X13477, X13478, X13479, X13487, X13488 Genomic DNA. Translation: CAA31830.1.
X06989 mRNA. Translation: CAA30050.1.
M33112
, M34862, M34863, M34864, M34865, M34866, M34867, M34868, M34869, M34870, M34871, M34872, M34873, M34874, M34876, M34877, M34878, M34879 Genomic DNA. Translation: AAB59502.1.
M34875
, M34862, M34863, M34864, M34865, M34866, M34867, M34868, M34869, M34870, M34871, M34872, M34873 Genomic DNA. Translation: AAB59501.1. Different termination.
D87675 Genomic DNA. Translation: BAA22264.1.
AK312326 mRNA. Translation: BAG35248.1.
AK295621 mRNA. Translation: BAG58500.1.
AY919674 Genomic DNA. Translation: AAW82435.1.
AP001439 Genomic DNA. No translation available.
AP001440 Genomic DNA. No translation available.
AP001441 Genomic DNA. No translation available.
AP001442 Genomic DNA. No translation available.
AP001443 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09958.1.
CH471079 Genomic DNA. Translation: EAX09959.1.
CH471079 Genomic DNA. Translation: EAX09960.1.
CH471079 Genomic DNA. Translation: EAX09961.1.
CH471079 Genomic DNA. Translation: EAX09963.1.
CH471079 Genomic DNA. Translation: EAX09965.1.
BC004369 mRNA. Translation: AAH04369.1.
BC065529 mRNA. Translation: AAH65529.1.
M35675 mRNA. Translation: AAA60163.1. Sequence problems.
M24547, M24546 Genomic DNA. Translation: AAC13654.1.
M28373 mRNA. Translation: AAA58727.1. Sequence problems.
X06982 mRNA. Translation: CAA30042.1.
X06981 mRNA. Translation: CAA30041.1.
M18734 mRNA. Translation: AAA51726.1.
M29270, M29269 Genomic DNA. Translation: AAA51768.1.
AB066441 mRNA. Translation: BAB71958.2.
M15533 mRNA. Translation: AAA35540.1.
M15532 mRNA. Translation: AAA51564.1.
M37896, M37895 Genomic DNA. Translation: AAA51727.1.
S45136 Genomic DNA. Translation: AAB23646.1.
S60317 Genomic DNA. Translation: AAC60601.2.
AF282245 mRNA. Translation: AAQ14327.1.
S60721 mRNA. Translation: AAB26263.2.
S61380 mRNA. Translation: AAB26264.2.
S61383 mRNA. Translation: AAB26265.2.
M16765 mRNA. Translation: AAA51722.1.
PIRiS01442.
QRHUA4. S02260.
RefSeqiNP_000475.1. NM_000484.3.
NP_001129488.1. NM_001136016.3.
NP_001129601.1. NM_001136129.2.
NP_001129602.1. NM_001136130.2.
NP_001129603.1. NM_001136131.2.
NP_001191230.1. NM_001204301.1.
NP_001191231.1. NM_001204302.1.
NP_001191232.1. NM_001204303.1.
NP_958816.1. NM_201413.2.
NP_958817.1. NM_201414.2.
UniGeneiHs.434980.

Genome annotation databases

EnsembliENST00000346798; ENSP00000284981; ENSG00000142192. [P05067-1]
ENST00000348990; ENSP00000345463; ENSG00000142192. [P05067-4]
ENST00000354192; ENSP00000346129; ENSG00000142192. [P05067-10]
ENST00000357903; ENSP00000350578; ENSG00000142192. [P05067-8]
ENST00000358918; ENSP00000351796; ENSG00000142192. [P05067-9]
ENST00000359726; ENSP00000352760; ENSG00000142192. [P05067-6]
ENST00000440126; ENSP00000387483; ENSG00000142192. [P05067-11]
GeneIDi351.
KEGGihsa:351.
UCSCiuc002ylz.3. human. [P05067-1]
uc002yma.3. human. [P05067-8]
uc002ymb.3. human. [P05067-4]
uc010glj.3. human. [P05067-10]
uc010glk.3. human.
uc011acj.2. human. [P05067-2]
uc021whz.1. human. [P05067-9]
uc021wia.1. human. [P05067-7]
uc021wib.1. human. [P05067-3]

Polymorphism databases

DMDMi112927.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Alzheimer Research Forum

APP mutations

AD mutations
GeneReviews
NIEHS-SNPs
Wikipedia

Amyloid beta entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00264 mRNA. Translation: CAA68374.1 .
X13466
, X13467 , X13468 , X13469 , X13470 , X13471 , X13472 , X13473 , X13474 , X13475 , X13476 , X13477 , X13478 , X13479 , X13487 , X13488 Genomic DNA. Translation: CAA31830.1 .
X06989 mRNA. Translation: CAA30050.1 .
M33112
, M34862 , M34863 , M34864 , M34865 , M34866 , M34867 , M34868 , M34869 , M34870 , M34871 , M34872 , M34873 , M34874 , M34876 , M34877 , M34878 , M34879 Genomic DNA. Translation: AAB59502.1 .
M34875
, M34862 , M34863 , M34864 , M34865 , M34866 , M34867 , M34868 , M34869 , M34870 , M34871 , M34872 , M34873 Genomic DNA. Translation: AAB59501.1 . Different termination.
D87675 Genomic DNA. Translation: BAA22264.1 .
AK312326 mRNA. Translation: BAG35248.1 .
AK295621 mRNA. Translation: BAG58500.1 .
AY919674 Genomic DNA. Translation: AAW82435.1 .
AP001439 Genomic DNA. No translation available.
AP001440 Genomic DNA. No translation available.
AP001441 Genomic DNA. No translation available.
AP001442 Genomic DNA. No translation available.
AP001443 Genomic DNA. No translation available.
CH471079 Genomic DNA. Translation: EAX09958.1 .
CH471079 Genomic DNA. Translation: EAX09959.1 .
CH471079 Genomic DNA. Translation: EAX09960.1 .
CH471079 Genomic DNA. Translation: EAX09961.1 .
CH471079 Genomic DNA. Translation: EAX09963.1 .
CH471079 Genomic DNA. Translation: EAX09965.1 .
BC004369 mRNA. Translation: AAH04369.1 .
BC065529 mRNA. Translation: AAH65529.1 .
M35675 mRNA. Translation: AAA60163.1 . Sequence problems.
M24547 , M24546 Genomic DNA. Translation: AAC13654.1 .
M28373 mRNA. Translation: AAA58727.1 . Sequence problems.
X06982 mRNA. Translation: CAA30042.1 .
X06981 mRNA. Translation: CAA30041.1 .
M18734 mRNA. Translation: AAA51726.1 .
M29270 , M29269 Genomic DNA. Translation: AAA51768.1 .
AB066441 mRNA. Translation: BAB71958.2 .
M15533 mRNA. Translation: AAA35540.1 .
M15532 mRNA. Translation: AAA51564.1 .
M37896 , M37895 Genomic DNA. Translation: AAA51727.1 .
S45136 Genomic DNA. Translation: AAB23646.1 .
S60317 Genomic DNA. Translation: AAC60601.2 .
AF282245 mRNA. Translation: AAQ14327.1 .
S60721 mRNA. Translation: AAB26263.2 .
S61380 mRNA. Translation: AAB26264.2 .
S61383 mRNA. Translation: AAB26265.2 .
M16765 mRNA. Translation: AAA51722.1 .
PIRi S01442.
QRHUA4. S02260.
RefSeqi NP_000475.1. NM_000484.3.
NP_001129488.1. NM_001136016.3.
NP_001129601.1. NM_001136129.2.
NP_001129602.1. NM_001136130.2.
NP_001129603.1. NM_001136131.2.
NP_001191230.1. NM_001204301.1.
NP_001191231.1. NM_001204302.1.
NP_001191232.1. NM_001204303.1.
NP_958816.1. NM_201413.2.
NP_958817.1. NM_201414.2.
UniGenei Hs.434980.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1AAP X-ray 1.50 A/B 287-344 [» ]
1AMB NMR - A 672-699 [» ]
1AMC NMR - A 672-699 [» ]
1AML NMR - A 672-711 [» ]
1BA4 NMR - A 672-711 [» ]
1BA6 NMR - A 672-711 [» ]
1BJB NMR - A 672-699 [» ]
1BJC NMR - A 672-699 [» ]
1BRC X-ray 2.50 I 287-342 [» ]
1CA0 X-ray 2.10 D/I 289-342 [» ]
1HZ3 NMR - A 681-706 [» ]
1IYT NMR - A 672-713 [» ]
1MWP X-ray 1.80 A 28-123 [» ]
1OWT NMR - A 124-189 [» ]
1QCM NMR - A 696-706 [» ]
1QWP NMR - A 696-706 [» ]
1QXC NMR - A 696-706 [» ]
1QYT NMR - A 696-706 [» ]
1TAW X-ray 1.80 B 287-344 [» ]
1TKN NMR - A 460-569 [» ]
1UO7 model - A 672-713 [» ]
1UO8 model - A 672-713 [» ]
1UOA model - A 672-713 [» ]
1UOI model - A 672-713 [» ]
1X11 X-ray 2.50 C/D 754-766 [» ]
1Z0Q NMR - A 672-713 [» ]
1ZE7 NMR - A 672-687 [» ]
1ZE9 NMR - A 672-687 [» ]
1ZJD X-ray 2.60 B 289-344 [» ]
2BEG NMR - A/B/C/D/E 672-713 [» ]
2BOM model - A/B 681-713 [» ]
2BP4 NMR - A 672-687 [» ]
2FJZ X-ray 1.61 A 133-189 [» ]
2FK1 X-ray 1.60 A 133-189 [» ]
2FK2 X-ray 1.65 A 133-189 [» ]
2FK3 X-ray 2.40 A/B/C/D/E/F/G/H 133-189 [» ]
2FKL X-ray 2.50 A/B 124-189 [» ]
2FMA X-ray 0.85 A 133-189 [» ]
2G47 X-ray 2.10 C/D 672-711 [» ]
2IPU X-ray 1.65 P/Q 672-679 [» ]
2LFM NMR - A 672-711 [» ]
2LLM NMR - A 686-726 [» ]
2LMN NMR - A/B/C/D/E/F/G/H/I/J/K/L 672-711 [» ]
2LMO NMR - A/B/C/D/E/F/G/H/I/J/K/L 672-711 [» ]
2LMP NMR - A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R 672-711 [» ]
2LMQ NMR - A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R 672-711 [» ]
2LNQ NMR - A/B/C/D/E/F/G/H 672-711 [» ]
2LOH NMR - A/B 686-726 [» ]
2LP1 NMR - A 671-770 [» ]
2LZ3 NMR - A/B 699-726 [» ]
2LZ4 NMR - A/B 699-726 [» ]
2M4J NMR - A/B/C/D/E/F/G/H/I 672-711 [» ]
2M9R NMR - A 672-711 [» ]
2M9S NMR - A 672-711 [» ]
2OTK NMR - C 672-711 [» ]
2R0W X-ray 2.50 Q 672-679 [» ]
2WK3 X-ray 2.59 C/D 672-713 [» ]
2Y29 X-ray 2.30 A 687-692 [» ]
2Y2A X-ray 1.91 A 687-692 [» ]
2Y3J X-ray 1.99 A/B/C/D/E/F/G/H 701-706 [» ]
2Y3K X-ray 1.90 A/B/C/D/E/F/G/H 706-713 [» ]
2Y3L X-ray 2.10 A/B/C/G 706-713 [» ]
3AYU X-ray 2.00 B 586-595 [» ]
3DXC X-ray 2.10 B/D 739-770 [» ]
3DXD X-ray 2.20 B/D 739-770 [» ]
3DXE X-ray 2.00 B/D 739-770 [» ]
3GCI X-ray 2.04 P 707-713 [» ]
3IFL X-ray 1.50 P 672-678 [» ]
3IFN X-ray 1.50 P 672-711 [» ]
3IFO X-ray 2.15 P/Q 672-678 [» ]
3IFP X-ray 2.95 P/Q/R/S 672-678 [» ]
3JTI X-ray 1.80 B 699-706 [» ]
3KTM X-ray 2.70 A/B/C/D/E/F/G/H 18-190 [» ]
3L33 X-ray 2.48 E/F/G/H 290-341 [» ]
3L81 X-ray 1.60 B 761-767 [» ]
3MOQ X-ray 2.05 A/B/C/D 689-712 [» ]
3MXC X-ray 2.00 L 754-762 [» ]
3MXY X-ray 2.30 L 754-762 [» ]
3NYJ X-ray 3.20 A 365-567 [» ]
3NYL X-ray 2.80 A 365-570 [» ]
3OVJ X-ray 1.80 A/B/C/D 687-692 [» ]
3OW9 X-ray 1.80 A/B 687-692 [» ]
3SV1 X-ray 3.30 D/E/F 754-767 [» ]
3U0T X-ray 2.50 E/F 701-711 [» ]
3UMH X-ray 2.00 A 370-575 [» ]
3UMI X-ray 2.40 A 370-575 [» ]
3UMK X-ray 2.60 A 370-575 [» ]
4HIX X-ray 2.20 A 672-699 [» ]
ProteinModelPortali P05067.
SMRi P05067. Positions 26-192, 287-342, 385-567, 683-728, 741-768.
ModBasei Search...

Protein-protein interaction databases

BioGridi 106848. 1970 interactions.
DIPi DIP-574N.
IntActi P05067. 110 interactions.
MINTi MINT-150767.

Chemistry

BindingDBi P05067.
ChEMBLi CHEMBL2487.

Protein family/group databases

MEROPSi I02.015.
TCDBi 1.C.50.1.2. the amyloid -protein peptide (app) family.

PTM databases

PhosphoSitei P05067.
UniCarbKBi P05067.

Polymorphism databases

DMDMi 112927.

2D gel databases

SWISS-2DPAGEi P05067.

Proteomic databases

PaxDbi P05067.
PRIDEi P05067.

Protocols and materials databases

DNASUi 351.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000346798 ; ENSP00000284981 ; ENSG00000142192 . [P05067-1 ]
ENST00000348990 ; ENSP00000345463 ; ENSG00000142192 . [P05067-4 ]
ENST00000354192 ; ENSP00000346129 ; ENSG00000142192 . [P05067-10 ]
ENST00000357903 ; ENSP00000350578 ; ENSG00000142192 . [P05067-8 ]
ENST00000358918 ; ENSP00000351796 ; ENSG00000142192 . [P05067-9 ]
ENST00000359726 ; ENSP00000352760 ; ENSG00000142192 . [P05067-6 ]
ENST00000440126 ; ENSP00000387483 ; ENSG00000142192 . [P05067-11 ]
GeneIDi 351.
KEGGi hsa:351.
UCSCi uc002ylz.3. human. [P05067-1 ]
uc002yma.3. human. [P05067-8 ]
uc002ymb.3. human. [P05067-4 ]
uc010glj.3. human. [P05067-10 ]
uc010glk.3. human.
uc011acj.2. human. [P05067-2 ]
uc021whz.1. human. [P05067-9 ]
uc021wia.1. human. [P05067-7 ]
uc021wib.1. human. [P05067-3 ]

Organism-specific databases

CTDi 351.
GeneCardsi GC21M027252.
HGNCi HGNC:620. APP.
HPAi CAB000157.
HPA001462.
MIMi 104300. phenotype.
104760. gene.
605714. phenotype.
neXtProti NX_P05067.
Orphaneti 1020. Early-onset autosomal dominant Alzheimer disease.
324723. Hereditary cerebral hemorrhage with amyloidosis, Arctic type.
100006. Hereditary cerebral hemorrhage with amyloidosis, Dutch type.
324718. Hereditary cerebral hemorrhage with amyloidosis, Flemish type.
324708. Hereditary cerebral hemorrhage with amyloidosis, Iowa type.
324713. Hereditary cerebral hemorrhage with amyloidosis, Italian type.
324703. Hereditary cerebral hemorrhage with amyloidosis, Piedmont type.
PharmGKBi PA24910.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG289770.
HOVERGENi HBG000051.
InParanoidi P05067.
KOi K04520.
OMAi THAHIVI.
OrthoDBi EOG7RNJZP.
PhylomeDBi P05067.
TreeFami TF317274.

Enzyme and pathway databases

BioCyci MetaCyc:ENSG00000142192-MONOMER.
Reactomei REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SABIO-RKi P05067.

Miscellaneous databases

ChiTaRSi app. human.
EvolutionaryTracei P05067.
GeneWikii Amyloid_precursor_protein.
GenomeRNAii 351.
NextBioi 1445.
PMAP-CutDBi P05067.
PROi P05067.
SOURCEi Search...

Gene expression databases

ArrayExpressi P05067.
Bgeei P05067.
Genevestigatori P05067.

Family and domain databases

Gene3Di 3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.230.10. 1 hit.
4.10.410.10. 1 hit.
InterProi IPR008155. Amyloid_glyco.
IPR013803. Amyloid_glyco_Abeta.
IPR011178. Amyloid_glyco_Cu-bd.
IPR024329. Amyloid_glyco_E2_domain.
IPR008154. Amyloid_glyco_extra.
IPR019744. Amyloid_glyco_extracell_CS.
IPR015849. Amyloid_glyco_heparin-bd.
IPR019745. Amyloid_glyco_intracell_CS.
IPR028866. APP.
IPR019543. APP_amyloid_C.
IPR002223. Prot_inh_Kunz-m.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view ]
PANTHERi PTHR23103:SF7. PTHR23103:SF7. 1 hit.
Pfami PF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
PF03494. Beta-APP. 1 hit.
PF00014. Kunitz_BPTI. 1 hit.
[Graphical view ]
PRINTSi PR00203. AMYLOIDA4.
PR00759. BASICPTASE.
PR00204. BETAAMYLOID.
SMARTi SM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.
[Graphical view ]
SUPFAMi SSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF57362. SSF57362. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEi PS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
PS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publicationsDownload
  1. "The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor."
    Kang J., Lemaire H.-G., Unterbeck A., Salbaum J.M., Masters C.L., Grzeschik K.-H., Multhaup G., Beyreuther K., Mueller-Hill B.
    Nature 325:733-736(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
    Tissue: Brain.
  2. "A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors."
    Ponte P., Gonzalez-Dewhitt P., Schilling J., Miller J., Hsu D., Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F., Cordell B.
    Nature 331:525-527(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
    Tissue: Brain.
  3. "The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons."
    Lemaire H.-G., Salbaum J.M., Multhaup G., Kang J., Bayney R.M., Unterbeck A., Beyreuther K., Mueller-Hill B.
    Nucleic Acids Res. 17:517-522(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP695).
  4. "Genomic organization of the human amyloid beta-protein precursor gene."
    Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.
    Gene 87:257-263(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
  5. Erratum
    Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.
    Gene 102:291-292(1991) [PubMed] [Europe PMC] [Abstract]
  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 G., Moenning U., Czech C., Prior R., Banati R., Schreiter-Gasser U., Bauer J., Masters C.L., Beyreuther K.
    J. Biol. Chem. 267:10804-10809(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L-APP733).
    Tissue: Leukocyte.
  7. "A novel method for making nested deletions and its application for sequencing of a 300 kb region of human APP locus."
    Hattori M., Tsukahara F., Furuhata Y., Tanahashi H., Hirose M., Saito M., Tsukuni S., Sakaki Y.
    Nucleic Acids Res. 25:1802-1808(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
  8. "Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639."
    Tang K., Wang C., Shen C., Sheng S., Ravid R., Jing N.
    Eur. J. Neurosci. 18:102-108(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP639), TISSUE SPECIFICITY.
    Tissue: Brain.
  9. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP770 AND 11).
    Tissue: Cerebellum and Hippocampus.
  10. NIEHS SNPs program
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-501.
  11. "The DNA sequence of human chromosome 21."
    Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A.
    , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
    Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  12. Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R.
    , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  13. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP305 AND APP751).
    Tissue: Eye and Pancreas.
  14. "A cDNA specifying the human amyloid beta precursor protein (ABPP) encodes a 95-kDa polypeptide."
    Schon E.A., Mita S., Sadlock J., Herbert J.
    Nucleic Acids Res. 16:9351-9351(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-10.
    Tissue: Liver.
  15. Erratum
    Schon E.A., Mita S., Sadlock J., Herbert J.
    Nucleic Acids Res. 16:11402-11402(1988)
    Cited for: SEQUENCE REVISION.
  16. "Characterization of the 5'-end region and the first two exons of the beta-protein precursor gene."
    La Fauci G., Lahiri D.K., Salton S.R., Robakis N.K.
    Biochem. Biophys. Res. Commun. 159:297-304(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75.
  17. "Purification of protease nexin II from human fibroblasts."
    van Nostrand W.E., Cunningham D.D.
    J. Biol. Chem. 262:8508-8514(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 18-50.
    Tissue: Fibroblast.
  18. "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
    Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
    Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 18-40.
    Tissue: Platelet.
  19. "Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease."
    Tanzi R.E., McClatchey A.I., Lamperti E.D., Villa-Komaroff L., Gusella J.F., Neve R.L.
    Nature 331:528-530(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 286-366.
  20. "Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity."
    Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H.
    Nature 331:530-532(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 287-367.
  21. "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 S.B., Salim M., Chou W.G., Sajdel-Sulkowska E.M., Majocha R.E., Marotta C.A.
    Proc. Natl. Acad. Sci. U.S.A. 85:929-933(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 507-770.
    Tissue: Brain cortex.
  22. "Regulation of amyloid protein precursor (APP) binding to collagen and mapping of the binding sites on APP and collagen type I."
    Beher D., Hesse L., Masters C.L., Multhaup G.
    J. Biol. Chem. 271:1613-1620(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 523-555, DOMAIN COLLAGEN-BINDING.
  23. "A system for studying the effect(s) of familial Alzheimer disease mutations on the processing of the beta-amyloid peptide precursor."
    Denman R.B., Rosenzcwaig R., Miller D.L.
    Biochem. Biophys. Res. Commun. 192:96-103(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 655-737, VARIANTS AD1 GLY-717; ILE-717 AND PHE-717.
  24. "Alzheimer's disease amyloid peptide is encoded by two exons and shows similarity to soybean trypsin inhibitor."
    Johnstone E.M., Chaney M.O., Moore R.E., Ward K.E., Norris F.H., Little S.P.
    Biochem. Biophys. Res. Commun. 163:1248-1255(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 656-737.
  25. "Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease."
    Wakutani Y., Watanabe K., Adachi Y., Wada-Isoe K., Urakami K., Ninomiya H., Saido T.C., Hashimoto T., Iwatsubo T., Nakashima K.
    J. Neurol. Neurosurg. Psych. 75:1039-1042(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 672-723, VARIANT AD1 ASN-678.
  26. "Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease."
    Roher A.E., Lowenson J.D., Clarke S., Woods A.S., Cotter R.J., Gowing E., Ball M.J.
    Proc. Natl. Acad. Sci. U.S.A. 90:10836-10840(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 672-713.
    Tissue: Blood vessel.
  27. "Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids."
    Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D., Sinha S., Schlossmacher M., Whaley J., Swindlehurst C.
    Nature 359:325-327(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 672-704, TISSUE SPECIFICITY.
  28. "The amino acid sequence of neuritic plaque amyloid from a familial Alzheimer's disease patient."
    Wisniewski T., Lalowski M., Levy E., Marques M.R.F., Frangione B.
    Ann. Neurol. 35:245-246(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 672-701 AND 707-713.
  29. "Characterization of beta-amyloid peptide from human cerebrospinal fluid."
    Vigo-Pelfrey C., Lee D., Keim P., Lieberburg I., Schenk D.B.
    J. Neurochem. 61:1965-1968(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 672-701.
    Tissue: Cerebrospinal fluid.
  30. "Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels."
    Pardridge W.M., Vinters H.V., Yang J., Eisenberg J., Choi T.B., Tourtellotte W.W., Huebner V., Shively J.E.
    J. Neurochem. 49:1394-1401(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 672-681.
    Tissue: Brain cortex.
  31. "Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease."
    Goldgaber D., Lerman M.I., McBride O.W., Saffiotti U., Gajdusek D.C.
    Science 235:877-880(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 674-770.
    Tissue: Brain.
  32. "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus."
    Tanzi R.E., Gusella J.F., Watkins P.C., Bruns G.A., St George-Hyslop P.H., Van Keuren M.L., Patterson D., Pagan S., Kurnit D.M., Neve R.L.
    Science 235:880-884(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 674-703.
    Tissue: Fetal brain.
  33. "An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid beta and amyloid precursor protein in human and cat cerebrospinal fluid."
    Brinkmalm G., Portelius E., Ohrfelt A., Mattsson N., Persson R., Gustavsson M.K., Vite C.H., Gobom J., Mansson J.E., Nilsson J., Halim A., Larson G., Ruetschi U., Zetterberg H., Blennow K., Brinkmalm A.
    J. Mass Spectrom. 47:591-603(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 609-713, GLYCOSYLATION AT SER-614; SER-623; SER-628; SER-679 AND SER-697.
    Tissue: Cerebrospinal fluid.
  34. "BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome."
    Sun X., He G., Song W.
    FASEB J. 20:1369-1376(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 691-698, CLEAVAGE BY THETA-SECRETASE.
  35. "A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein."
    de Sauvage F., Octave J.-N.
    Science 245:651-653(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
    Tissue: Brain.
  36. "Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides."
    Robakis N.K., Ramakrishna N., Wolfe G., Wisniewski H.M.
    Proc. Natl. Acad. Sci. U.S.A. 84:4190-4194(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
    Tissue: Brain.
  37. "The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene."
    Pangalos M.N., Efthimiopoulos S., Shioi J., Robakis N.K.
    J. Biol. Chem. 270:10388-10391(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF L-APP733, MUTAGENESIS OF SER-656.
  38. "Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions."
    Walter M.F., Mason P.E., Mason R.P.
    Biochem. Biophys. Res. Commun. 233:760-764(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF BETA-AMYLOID PEPTIDE AS LIPID PEROXIDATION INHIBITOR, MUTAGENESIS OF MET-706.
  39. "Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins."
    Kontush A.
    Cell. Mol. Neurobiol. 21:299-315(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION OF BETA-AMYLOID AS ANTIOXIDANT.
  40. "The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II."
    Oltersdorf T., Fritz L.C., Schenk D.B., Lieberburg I., Johnson-Wood K.L., Beattie E.C., Ward P.J., Blacher R.W., Dovey H.F., Sinha S.
    Nature 341:144-147(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTITY OF APP WITH NEXIN-II.
  41. "Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease amyloid protein precursor."
    Kido H., Fukutomi A., Schilling J., Wang Y., Cordell B., Katunuma N.
    Biochem. Biophys. Res. Commun. 167:716-721(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEASE-SPECIFICITY OF INHIBITOR DOMAIN.
  42. "A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease."
    Bush A.I., Multhaup G., Moir R.D., Williamson T.G., Small D.H., Rumble B., Pollwein P., Beyreuther K., Masters C.L.
    J. Biol. Chem. 268:16109-16112(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: EXTRACELLULAR ZINC-BINDING DOMAIN.
  43. "Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o)."
    Nishimoto I., Okamoto T., Matsuura Y., Takahashi S., Okamoto T., Murayama Y., Ogata E.
    Nature 362:75-79(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH G(O).
  44. "The beta A4 amyloid precursor protein binding to copper."
    Hesse L., Beher D., Masters C.L., Multhaup G.
    FEBS Lett. 349:109-116(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: EXTRACELLULAR COPPER-BINDING DOMAIN, MUTAGENESIS OF HIS-137; MET-141; CYS-144; HIS-147 AND HIS-151.
  45. "A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth."
    Small D.H., Nurcombe V., Reed G., Clarris H., Moir R., Beyreuther K., Masters C.L.
    J. Neurosci. 14:2117-2127(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: N-TERMINAL HEPARIN-BINDING DOMAIN, MUTAGENESIS OF 99-LYS--ARG-102.
  46. "Familial Alzheimer's disease-linked mutations at Val717 of amyloid precursor protein are specific for the increased secretion of A beta 42(43)."
    Maruyama K., Tomita T., Shinozaki K., Kume H., Asada H., Saido T.C., Ishiura S., Iwatsubo T., Obata K.
    Biochem. Biophys. Res. Commun. 227:730-735(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF VAL-717.
  47. "APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein."
    Chow N., Korenberg J.R., Chen X.-N., Neve R.L.
    J. Biol. Chem. 271:11339-11346(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APP-BP1.
  48. "The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein."
    Borg J.-P., Ooi J., Levy E., Margolis B.
    Mol. Cell. Biol. 16:6229-6241(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APBA1 AND APBB1, MUTAGENESIS OF TYR-728; TYR-757; ASN-759 AND TYR-762.
  49. "Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein."
    Guenette S.Y., Chen J., Jondro P.D., Tanzi R.E.
    Proc. Natl. Acad. Sci. U.S.A. 93:10832-10837(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APBB2.
  50. "Expression and analysis of heparin-binding regions of the amyloid precursor protein of Alzheimer's disease."
    Mok S.S., Sberna G., Heffernan D., Cappai R., Galatis D., Clarris H.J., Sawyer W.H., Beyreuther K., Masters C.L., Small D.H.
    FEBS Lett. 415:303-307(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: HEPARIN-BINDING DOMAINS.
  51. "An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease."
    Yan S.D., Fu J., Soto C., Chen X., Zhu H., Al-Mohanna F., Collinson K., Zhu A., Stern E., Saido T., Tohyama M., Ogawa S., Roher A., Stern D.
    Nature 389:689-695(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF BETA-AMYLOID PEPTIDE WITH HADH2.
    Tissue: Brain.
  52. "PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein."
    Zheng P., Eastman J., Vande Pol S., Pimplikar S.W.
    Proc. Natl. Acad. Sci. U.S.A. 95:14745-14750(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APPBP2, MUTAGENESIS OF TYR-728.
  53. "Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease."
    Liu S.T., Howlett G., Barrow C.J.
    Biochemistry 38:9373-9378(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: BETA-AMYLOID ZINC-BINDING, MUTAGENESIS OF ARG-676; TYR-681 AND HIS-684.
  54. "Methionine residue 35 is important in amyloid beta-peptide-associated free radical oxidative stress."
    Varadarajan S., Yatin S., Kanski J., Jahanshahi F., Butterfield D.A.
    Brain Res. Bull. 50:133-141(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: IMPORTANCE OF MET-706 IN FREE RADICAL OXIDATIVE STRESS, MUTAGENESIS OF MET-706.
  55. "Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein."
    Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S., Kirino Y., Suzuki T.
    J. Biol. Chem. 274:2243-2254(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APBA2.
  56. "Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42."
    Perez R.G., Soriano S., Hayes J.D., Ostaszewski B., Xia W., Selkoe D.J., Chen X., Stokin G.B., Koo E.H.
    J. Biol. Chem. 274:18851-18856(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENDOCYTOSIS SIGNAL, MUTAGENESIS OF TYR-728; GLY-756; TYR-757; ASN-759; PRO-760 AND TYR-762.
  57. "Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein."
    Ruiz F.H., Gonzalez M., Bodini M., Opazo C., Inestrosa N.C.
    J. Neurochem. 73:1288-1292(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: IMPORTANCE OF CYS-144 IN COPPER REDUCTION, MUTAGENESIS OF CYS-144 AND 147-HIS--HIS-149.
  58. "Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides."
    Tokuda T., Calero M., Matsubara E., Vidal R., Kumar A., Permanne B., Zlokovic B., Smith J.D., Ladu M.J., Rostagno A., Frangione B., Ghiso J.
    Biochem. J. 348:359-365(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF BETA-AMYLOID WITH APOE.
  59. "Beta-amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology."
    Wang H.-Y., Lee D.H.S., D'Andrea M.R., Peterson P.A., Shank R.P., Reitz A.B.
    J. Biol. Chem. 275:5626-5632(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF BETA-APP42 WITH CHRNA7.
  60. "Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor."
    Passer B., Pellegrini L., Russo C., Siegel R.M., Lenardo M.J., Schettini G., Bachmann M., Tabaton M., D'Adamio L.
    J. Alzheimers Dis. 2:289-301(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF GAMMA-CTFS BY MASS SPECTROMETRY, MUTAGENESIS OF ASP-739.
  61. "Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages."
    Yazawa H., Yu Z.-X., Takeda K., Le Y., Gong W., Ferrans V.J., Oppenheim J.J., Li C.C.H., Wang J.M.
    FASEB J. 15:2454-2462(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FPRL1.
  62. "Beta-amyloid peptide-induced apoptosis regulated by a novel protein containing a G protein activation module."
    Kajkowski E.M., Lo C.F., Ning X., Walker S., Sofia H.J., Wang W., Edris W., Chanda P., Wagner E., Vile S., Ryan K., McHendry-Rinde B., Smith S.C., Wood A., Rhodes K.J., Kennedy J.D., Bard J., Jacobsen J.S., Ozenberger B.A.
    J. Biol. Chem. 276:18748-18756(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BBP.
  63. "Alzheimer's disease amyloid-beta binds copper and zinc to generate an allosterically ordered structure containing superoxide dismutase-like subunits."
    Curtain C.C., Ali F., Volitakis I., Cherny R.A., Norton R.S., Beyreuther K., Barrow C.J., Masters C.L., Bush A.I., Barnham K.J.
    J. Biol. Chem. 276:20466-20473(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: BETA-AMYLOID COPPER AND ZINC-BINDING.
  64. "Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease."
    Scheuermann S., Hambsch B., Hesse L., Stumm J., Schmidt C., Beher D., Bayer T.A., Beyreuther K., Multhaup G.
    J. Biol. Chem. 276:33923-33929(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  65. "The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner."
    Kimberly W.T., Zheng J.B., Guenette S.Y., Selkoe D.J.
    J. Biol. Chem. 276:40288-40292(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APBB1, FUNCTION, SUBCELLULAR LOCATION.
  66. "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and modulates its physiological function."
    Ohsawa I., Takamura C., Kohsaka S.
    J. Neurochem. 76:1411-1420(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FBLN1.
  67. "Direct interaction of soluble human recombinant tau protein with Abeta 1-42 results in tau aggregation and hyperphosphorylation by tau protein kinase II."
    Rank K.B., Pauley A.M., Bhattacharya K., Wang Z., Evans D.B., Fleck T.J., Johnston J.A., Sharma S.K.
    FEBS Lett. 514:263-268(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPT, FUNCTION.
  68. "Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP)."
    Scheinfeld M.H., Roncarati R., Vito P., Lopez P.A., Abdallah M., D'Adamio L.
    J. Biol. Chem. 277:3767-3775(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPK8IP1, MUTAGENESIS OF TYR-757.
  69. "Contrasting species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein."
    White A.R., Multhaup G., Galatis D., McKinstry W.J., Parker M.W., Pipkorn R., Beyreuther K., Masters C.L., Cappai R.
    J. Neurosci. 22:365-376(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: COPPER-MEDIATED LIPID PEROXIDATION, MUTAGENESIS OF HIS-147 AND HIS-151.
  70. "The galvanization of beta-amyloid in Alzheimer's disease."
    Bush A.I., Tanzi R.E.
    Proc. Natl. Acad. Sci. U.S.A. 99:7317-7319(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ZINC-BINDING.
  71. "Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease."
    Watanabe N., Araki W., Chui D.H., Makifuchi T., Ihara Y., Tabira T.
    FASEB J. 18:1013-1015(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, ASSOCIATION OF AMYLOID FIBRILS WITH GCP1.
  72. "Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its processing in an isoform-specific manner."
    Ghersi E., Noviello C., D'Adamio L.
    J. Biol. Chem. 279:49105-49112(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ANKS1B.
  73. "Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein."
    Suzuki T., Oishi M., Marshak D.R., Czernik A.J., Nairn A.C., Greengard P.
    EMBO J. 13:1114-1122(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-743.
  74. "Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations."
    Walter J., Capell A., Hung A.Y., Langen H., Schnoelzer M., Thinakaran G., Sisodia S.S., Selkoe D.J., Haass C.
    J. Biol. Chem. 272:1896-1903(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY CASEIN KINASES, MUTAGENESIS OF SER-198 AND SER-206.
  75. "Copper-binding amyloid precursor protein undergoes a site-specific fragmentation in the reduction of hydrogen peroxide."
    Multhaup G., Ruppert T., Schlicksupp A., Hesse L., Bill E., Pipkorn R., Masters C.L., Beyreuther K.
    Biochemistry 37:7224-7230(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: COPPER-BINDING, DISULFIDE BOND FORMATION.
  76. "Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation."
    Gervais F.G., Xu D., Robertson G.S., Vaillancourt J.P., Zhu Y., Huang J., LeBlanc A., Smith D., Rigby M., Shearman M.S., Clarke E.E., Zheng H., van der Ploeg L.H.T., Ruffolo S.C., Thornberry N.A., Xanthoudakis S., Zamboni R.J., Roy S., Nicholson D.W.
    Cell 97:395-406(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY CASPASES, MUTAGENESIS OF ASP-739.
  77. "Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation."
    Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C., Kirino Y., Greengard P., Suzuki T.
    J. Neurosci. 19:4421-4427(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, MUTAGENESIS OF THR-743.
  78. "Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2."
    Walter J., Schindzielorz A., Hartung B., Haass C.
    J. Biol. Chem. 275:23523-23529(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF CASEIN KINASE PHOSPHORYLATION, MUTAGENESIS OF SER-198 AND SER-206.
  79. "A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor."
    Lu D.C., Rabizadeh S., Chandra S., Shayya R.F., Ellerby L.M., Ye X., Salvesen G.S., Koo E.H., Bredesen D.E.
    Nat. Med. 6:397-404(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY CASPASES, MUTAGENESIS OF ASP-739.
  80. "Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid."
    Ando K., Iijima K., Elliott J.I., Kirino Y., Suzuki T.
    J. Biol. Chem. 276:40353-40361(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, INTERACTION WITH APBB1, MUTAGENESIS OF THR-743.
  81. "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 C.L., Brownlees J., Grierson A.J., Kesavapany S., Lau K.-F., McLoughlin D.M., Miller C.C.J.
    J. Neurochem. 76:316-320(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY MAPK10, MUTAGENESIS OF THR-743.
  82. "A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing."
    Weidemann A., Eggert S., Reinhard F.B.M., Vogel M., Paliga K., Baier G., Masters C.L., Beyreuther K., Evin G.
    Biochemistry 41:2825-2835(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE AT LEU-720.
  83. "Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc."
    Tarr P.E., Roncarati R., Pelicci G., Pelicci P.G., D'Adamio L.
    J. Biol. Chem. 277:16798-16804(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES, INTERACTION WITH SHC1, MUTAGENESIS OF THR-743 AND TYR-757.
  84. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-542.
    Tissue: Plasma.
  85. "Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease."
    Dyrks T., Weidemann A., Multhaup G., Salbaum J.M., Lemaire H.-G., Kang J., Mueller-Hill B., Masters C.L., Beyreuther K.
    EMBO J. 7:949-957(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: SIGNAL SEQUENCE CLEAVAGE SITE, TOPOLOGY.
  86. "A cell biological perspective on Alzheimer's disease."
    Annaert W., De Strooper B.
    Annu. Rev. Cell Dev. Biol. 18:25-51(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  87. "Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein."
    Andersen O.M., Reiche J., Schmidt V., Gotthardt M., Spoelgen R., Behlke J., von Arnim C.A., Breiderhoff T., Jansen P., Wu X., Bales K.R., Cappai R., Masters C.L., Gliemann J., Mufson E.J., Hyman B.T., Paul S.M., Nykjaer A., Willnow T.E.
    Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SORL1, SUBCELLULAR LOCATION.
  88. "Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells."
    Nakaya T., Kawai T., Suzuki T.
    J. Biol. Chem. 283:19119-19131(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH APBB1.
  89. "BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2."
    Matsuda S., Matsuda Y., D'Adamio L.
    J. Biol. Chem. 284:15815-15825(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ITM2C.
  90. "APP binds DR6 to trigger axon pruning and neuron death via distinct caspases."
    Nikolaev A., McLaughlin T., O'Leary D.D.M., Tessier-Lavigne M.
    Nature 457:981-989(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CLEAVAGE, INTERACTION WITH TNFRSF21.
  91. "RAGE-mediated signaling contributes to intraneuronal transport of amyloid-{beta} and neuronal dysfunction."
    Takuma K., Fang F., Zhang W., Yan S., Fukuzaki E., Du H., Sosunov A., McKhann G., Funatsu Y., Nakamichi N., Nagai T., Mizoguchi H., Ibi D., Hori O., Ogawa S., Stern D.M., Yamada K., Yan S.S.
    Proc. Natl. Acad. Sci. U.S.A. 106:20021-20026(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH AGER.
  92. "Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease."
    He G., Luo W., Li P., Remmers C., Netzer W.J., Hendrick J., Bettayeb K., Flajolet M., Gorelick F., Wennogle L.P., Greengard P.
    Nature 467:95-98(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GSAP.
  93. "Initial characterization of the human central proteome."
    Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
    BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  94. "Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid beta-peptides in human cerebrospinal fluid."
    Halim A., Brinkmalm G., Ruetschi U., Westman-Brinkmalm A., Portelius E., Zetterberg H., Blennow K., Larson G., Nilsson J.
    Proc. Natl. Acad. Sci. U.S.A. 108:11848-11853(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-633; THR-651; THR-652; SER-656; THR-663 AND SER-667 PROTEOLYTIC PROCESSING, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
  95. "MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and induces its fibrillization."
    Zhang C., Liu Y., Gilthorpe J., van der Maarel J.R.
    PLoS ONE 7:E32953-E32953(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH S100A9.
  96. "X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor."
    Hynes T.R., Randal M., Kennedy L.A., Eigenbrot C., Kossiakof A.A.
    Biochemistry 29:10018-10022(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 287-344.
  97. "Sequential NMR resonance assignment and structure determination of the Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor protein."
    Heald S.L., Tilton R.F. Jr., Hammond L.S., Lee A., Bayney R.M., Kamarck M.E., Ramabhadran T.V., Dreyer R.N., Davis G., Unterbeck A., Tamburini P.P.
    Biochemistry 30:10467-10478(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 289-344.
  98. "Solution structure of residues 1-28 of the amyloid beta-peptide."
    Talafous J., Marcinowski K.J., Klopman G., Zagorski M.G.
    Biochemistry 33:7788-7796(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 672-699.
  99. "Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease."
    Sticht H., Bayer P., Willbold D., Dames S., Hilbich C., Beyreuther K., Frank R.W., Rosch P.
    Eur. J. Biochem. 233:293-298(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 672-711.
  100. "Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment."
    Kohno T., Kobayashi K., Maeda T., Sato K., Takashima A.
    Biochemistry 35:16094-16104(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 696-706.
  101. "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 A.J., Hynes T.R., Pelletier L.A., Wells J.A., Kossiakoff A.A.
    Protein Sci. 6:1806-1824(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF KUNITZ DOMAIN IN COMPLEX WITH CHYMOTRYPSIN; TRYPSIN AND BASIC PANCREATIC TRYPSIN INHIBITOR.
  102. "Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?"
    Coles M., Bicknell W., Watson A.A., Fairlie D.P., Craik D.J.
    Biochemistry 37:11064-11077(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 672-711.
  103. "Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein."
    Rossjohn J., Cappai R., Feil S.C., Henry A., McKinstry W.J., Galatis D., Hesse L., Multhaup G., Beyreuther K., Masters C.L., Parker M.W.
    Nat. Struct. Biol. 6:327-331(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 28-123.
  104. "Substitutions at codon 22 of Alzheimer's Abeta peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells."
    Miravalle L., Tokuda T., Chiarle R., Giaccone G., Bugiani O., Tagliavini F., Frangione B., Ghiso J.
    J. Biol. Chem. 275:27110-27116(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE OF CAA-APP VARIANTS.
  105. "The Alzheimer's peptide a beta adopts a collapsed coil structure in water."
    Zhang S., Iwata K., Lachenmann M.J., Peng J.W., Li S., Stimson E.R., Lu Y., Felix A.M., Maggio J.E., Lee J.P.
    J. Struct. Biol. 130:130-141(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 681-706.
  106. "Solution structures in aqueous SDS micelles of two amyloid beta peptides of Abeta(1-28) mutated at the alpha-secretase cleavage site."
    Poulsen S.-A., Watson A.A., Craik D.J.
    J. Struct. Biol. 130:142-152(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 672-699.
  107. "The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain."
    Wang Y., Ha Y.
    Mol. Cell 15:343-353(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 346-551, PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, MUTAGENESIS OF ARG-499 AND LYS-503.
  108. "Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism."
    Shen Y., Joachimiak A., Rosner M.R., Tang W.-J.
    Nature 443:870-874(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 672-711 IN COMPLEX WITH IDE.
  109. "Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution."
    Kong G.K., Adams J.J., Cappai R., Parker M.W.
    Acta Crystallogr. F 63:819-824(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 133-189, DISULFIDE BONDS.
  110. "Structural studies of the Alzheimer's amyloid precursor protein copper-binding domain reveal how it binds copper ions."
    Kong G.K., Adams J.J., Harris H.H., Boas J.F., Curtain C.C., Galatis D., Masters C.L., Barnham K.J., McKinstry W.J., Cappai R., Parker M.W.
    J. Mol. Biol. 367:148-161(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 133-189 IN COMPLEXES WITH COPPER IONS, DISULFIDE BONDS.
  111. "Molecular basis for passive immunotherapy of Alzheimer's disease."
    Gardberg A.S., Dice L.T., Ou S., Rich R.L., Helmbrecht E., Ko J., Wetzel R., Myszka D.G., Patterson P.H., Dealwis C.
    Proc. Natl. Acad. Sci. U.S.A. 104:15659-15664(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 672-679 IN COMPLEX WITH IGG.
  112. "Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease."
    Basi G.S., Feinberg H., Oshidari F., Anderson J., Barbour R., Baker J., Comery T.A., Diep L., Gill D., Johnson-Wood K., Goel A., Grantcharova K., Lee M., Li J., Partridge A., Griswold-Prenner I., Piot N., Walker D.
    , Widom A., Pangalos M.N., Seubert P., Jacobsen J.S., Schenk D., Weis W.I.
    J. Biol. Chem. 285:3417-3427(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 672-678 IN COMPLEXES WITH ANTIBODY FAB FRAGMENTS.
  113. "Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein."
    Dahms S.O., Hoefgen S., Roeser D., Schlott B., Guhrs K.H., Than M.E.
    Proc. Natl. Acad. Sci. U.S.A. 107:5381-5386(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 18-190, PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, SUBUNIT, DISULFIDE BONDS.
  114. "Framing beta-amyloid."
    Hardy J.
    Nat. Genet. 1:233-234(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON VARIANTS.
  115. "Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type."
    Levy E., Carman M.D., Fernandez-Madrid I.J., Power M.D., Lieberburg I., van Duinen S.G., Bots G.T.A.M., Luyendijk W., Frangione B.
    Science 248:1124-1126(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CAA-APP GLN-693.
  116. "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease."
    Goate A., Chartier-Harlin M.-C., Mullan M., Brown J., Crawford F., Fidani L., Giuffra L., Haynes A., Irving N., James L., Mant R., Newton P., Rooke K., Roques P., Talbot C., Pericak-Vance M., Roses A.D., Williamson R.
    , Rossor M., Owen M., Hardy J.
    Nature 349:704-706(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-717.
  117. "The 717Val-->Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups."
    Yoshioka K., Miki T., Katsuya T., Ogihara T., Sakaki Y.
    Biochem. Biophys. Res. Commun. 178:1141-1146(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-717.
  118. "Mis-sense mutation Val->Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease."
    Naruse S., Igarashi S., Kobayashi H., Aoki K., Inuzuka T., Kaneko K., Shimizu T., Iihara K., Kojima T., Miyatake T., Tsuji S.
    Lancet 337:978-979(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-717.
  119. "Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene."
    Chartier-Harlin M.-C., Crawford F., Houlden H., Warren A., Hughes D., Fidani L., Goate A., Rossor M., Roques P., Hardy J., Mullan M.
    Nature 353:844-846(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 GLY-717.
  120. "A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease."
    Murrell J.R., Farlow M., Ghetti B., Benson M.D.
    Science 254:97-99(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 PHE-717.
  121. "Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region."
    Kamino K., Orr H.T., Payami H., Wijsman E.M., Alonso M.E., Pulst S.M., Anderson L., O'Dahl S., Nemens E., White J.A., Sadovnick A.D., Ball M.J., Kaye J., Warren A., McInnis M.G., Antonarakis S.E., Korenberg J.R., Sharma V.
    , Kukull W., Larson E., Heston L.L., Martin G.M., Bird T.D., Schellenberg G.D.
    Am. J. Hum. Genet. 51:998-1014(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 GLY-693.
  122. "Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene."
    Hendriks L., van Duijn C.M., Cras P., Cruts M., Van Hul W., van Harskamp F., Warren A., McInnis M.G., Antonarakis S.E., Martin J.J., Hofman A., Van Broeckhoven C.
    Nat. Genet. 1:218-221(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 GLY-692.
  123. "A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid."
    Mullan M., Crawford F., Axelman K., Houlden H., Lilius L., Winblad B., Lannfelt L.
    Nat. Genet. 1:345-347(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 670-ASN-LEU-671.
  124. "Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia."
    Jones C.T., Morris S., Yates C.M., Moffoot A., Sharpe C., Brock D.J.H., St Clair D.
    Nat. Genet. 1:306-309(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT VAL-713.
  125. "More missense in amyloid gene."
    Carter D.A., Desmarais E., Bellis M., Campion D., Clerget-Darpoux F., Brice A., Agid Y., Jaillard-Serradt A., Mallet J.
    Nat. Genet. 2:255-256(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 THR-713.
  126. "Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease with APP717 mutations."
    Liepnieks J.J., Ghetti B., Farlow M., Roses A.D., Benson M.D.
    Biochem. Biophys. Res. Commun. 197:386-392(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS AD1 ILE-717 AND PHE-717.
  127. "Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late-onset Alzheimer's disease."
    Peacock M.L., Murman D.L., Sima A.A.F., Warren J.T. Jr., Roses A.D., Fink J.K.
    Ann. Neurol. 35:432-438(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ASP-665.
  128. "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 M., Murrell J., Ghetti B., Unverzagt F., Zeldenrust S., Benson M.D.
    Neurology 44:105-111(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 PHE-717.
  129. "A mutation in codon 717 of the amyloid precursor protein gene in an Australian family with Alzheimer's disease."
    Brooks W.S., Martins R.N., De Voecht J., Nicholson G.A., Schofield P.R., Kwok J.B.J., Fisher C., Yeung L.U., Van Broeckhoven C.
    Neurosci. Lett. 199:183-186(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-717.
  130. "A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43)."
    Eckman C.B., Mehta N.D., Crook R., Perez-Tur J., Prihar G., Pfeiffer E., Graff-Radford N., Hinder P., Yager D., Zenk B., Refolo L.M., Prada C.M., Younkin S.G., Hutton M., Hardy J.
    Hum. Mol. Genet. 6:2087-2089(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 VAL-716.
  131. "Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation."
    Cras P., van Harskamp F., Hendriks L., Ceuterick C., van Duijn C.M., Stefanko S.Z., Hofman A., Kros J.M., Van Broeckhoven C., Martin J.J.
    Acta Neuropathol. 96:253-260(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 GLY-692, CHARACTERIZATION OF PHENOTYPE.
  132. "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 K., Dumanchin C., Barelli H., Warter J.-M., Brice A., Campion D., Frebourg T., Checler F.
    Proc. Natl. Acad. Sci. U.S.A. 96:4119-4124(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 MET-715, CHARACTERIZATION OF VARIANT AD1 MET-715.
  133. "High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes."
    Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.
    Am. J. Hum. Genet. 66:110-117(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-717.
  134. "Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis."
    Kwok J.B.J., Li Q.X., Hallupp M., Whyte S., Ames D., Beyreuther K., Masters C.L., Schofield P.R.
    Ann. Neurol. 47:249-253(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 PRO-723.
  135. "Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene."
    Murrell J.R., Hake A.M., Quaid K.A., Farlow M.R., Ghetti B.
    Arch. Neurol. 57:885-887(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 LEU-717.
  136. "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 S., De Jonghe C., Cruts M., Kleinert R., Wang R., Mercken M., De Strooper B., Vanderstichele H., Loefgren A., Vanderhoeven I., Backhovens H., Vanmechelen E., Kroisel P.M., Van Broeckhoven C.
    Hum. Mol. Genet. 9:2589-2598(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-714, CHARACTERIZATION OF VARIANT AD1 ILE-714, MUTAGENESIS OF VAL-717.
  137. "Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy."
    Grabowski T.J., Cho H.S., Vonsattel J.P.G., Rebeck G.W., Greenberg S.M.
    Ann. Neurol. 49:697-705(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CAA-APP ASN-694.
  138. "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 D.M., Hartley D.M., Condron M.M., Selkoe D.J., Teplow D.B.
    Biochem. J. 355:869-877(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT AD1 GLY-692.
  139. "The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation."
    Nilsberth C., Westlind-Danielsson A., Eckman C.B., Condron M.M., Axelman K., Forsell C., Stenh C., Luthman J., Teplow D.B., Younkin S.G., Naeslund J., Lannfelt L.
    Nat. Neurosci. 4:887-893(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 GLY-693.
  140. "An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala)."
    Pasalar P., Najmabadi H., Noorian A.R., Moghimi B., Jannati A., Soltanzadeh A., Krefft T., Crook R., Hardy J.
    Neurology 58:1574-1575(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ALA-714.
  141. "Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation."
    Greenberg S.M., Shin Y., Grabowski T.J., Cooper G.E., Rebeck G.W., Iglesias S., Chapon F., Tournier-Lasserve E., Baron J.-C.
    Neurology 60:1020-1022(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CAA-APP ASN-694.
  142. "A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene."
    Rossi G., Giaccone G., Maletta R., Morbin M., Capobianco R., Mangieri M., Giovagnoli A.R., Bizzi A., Tomaino C., Perri M., Di Natale M., Tagliavini F., Bugiani O., Bruni A.C.
    Neurology 63:910-912(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 THR-713.
  143. "A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy."
    Obici L., Demarchi A., de Rosa G., Bellotti V., Marciano S., Donadei S., Arbustini E., Palladini G., Diegoli M., Genovese E., Ferrari G., Coverlizza S., Merlini G.
    Ann. Neurol. 58:639-644(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CAA-APP VAL-705.
  144. "An African American family with early-onset Alzheimer disease and an APP (T714I) mutation."
    Edwards-Lee T., Ringman J.M., Chung J., Werner J., Morgan A., St George-Hyslop P.H., Thompson P., Dutton R., Mlikotic A., Rogaeva E., Hardy J.
    Neurology 64:377-379(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AD1 ILE-714.

Entry nameiA4_HUMAN
AccessioniPrimary (citable) accession number: P05067
Secondary accession number(s): B2R5V1
, B4DII8, D3DSD1, D3DSD2, D3DSD3, P09000, P78438, Q13764, Q13778, Q13793, Q16011, Q16014, Q16019, Q16020, Q6GSC0, Q8WZ99, Q9BT38, Q9UC33, Q9UCA9, Q9UCB6, Q9UCC8, Q9UCD1, Q9UQ58
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: November 1, 1991
Last modified: March 19, 2014
This is version 225 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM

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