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Protein

Amyloid-beta A4 protein

Gene

APP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.By similarity
Amyloid-beta 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. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.
Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.By similarity
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).

Miscellaneous

Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei144Required for Cu(2+) reduction1
Metal bindingi147Copper 11
Metal bindingi151Copper 11
Metal bindingi168Copper 11
Sitei301 – 302Reactive bond2
Metal bindingi677Copper or zinc 21
Metal bindingi681Copper or zinc 2Curated1
Metal bindingi684Copper or zinc 21
Metal bindingi685Copper or zinc 21
Sitei704Implicated in free radical propagationBy similarity1
Sitei706Susceptible to oxidation1 Publication1

GO - Molecular functioni

  • acetylcholine receptor activator activity Source: ARUK-UCL
  • acetylcholine receptor binding Source: UniProtKB
  • amylin binding Source: ARUK-UCL
  • apolipoprotein binding Source: ARUK-UCL
  • chaperone binding Source: ARUK-UCL
  • chemoattractant activity Source: ARUK-UCL
  • DNA binding Source: UniProtKB
  • enzyme binding Source: ParkinsonsUK-UCL
  • ephrin receptor binding Source: ARUK-UCL
  • frizzled binding Source: ARUK-UCL
  • growth factor receptor binding Source: Ensembl
  • heparan sulfate binding Source: ARUK-UCL
  • heparan sulfate proteoglycan binding Source: ARUK-UCL
  • heparin binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • low-density lipoprotein particle receptor binding Source: ARUK-UCL
  • peptidase activator activity Source: Ensembl
  • protein dimerization activity Source: ARUK-UCL
  • protein heterodimerization activity Source: ARUK-UCL
  • protein homodimerization activity Source: ARUK-UCL
  • PTB domain binding Source: BHF-UCL
  • receptor activator activity Source: ARUK-UCL
  • receptor binding Source: ARUK-UCL
  • serine-type endopeptidase inhibitor activity Source: UniProtKB
  • transition metal ion binding Source: InterPro

GO - Biological processi

  • activation of MAPK activity Source: ARUK-UCL
  • activation of MAPKKK activity Source: ARUK-UCL
  • adult locomotory behavior Source: UniProtKB
  • amyloid fibril formation Source: ParkinsonsUK-UCL
  • antibacterial humoral response Source: UniProtKB
  • antifungal humoral response Source: UniProtKB
  • antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
  • associative learning Source: ARUK-UCL
  • astrocyte activation Source: ARUK-UCL
  • astrocyte activation involved in immune response Source: ARUK-UCL
  • axo-dendritic transport Source: UniProtKB
  • axon midline choice point recognition Source: UniProtKB
  • axonogenesis Source: UniProtKB
  • calcium-mediated signaling Source: ARUK-UCL
  • cell adhesion Source: UniProtKB-KW
  • cellular copper ion homeostasis Source: UniProtKB
  • cellular process Source: ParkinsonsUK-UCL
  • cellular protein metabolic process Source: Reactome
  • cellular response to amyloid-beta Source: ARUK-UCL
  • cellular response to cAMP Source: Ensembl
  • cellular response to nerve growth factor stimulus Source: Ensembl
  • cellular response to norepinephrine stimulus Source: Ensembl
  • cholesterol metabolic process Source: Ensembl
  • collateral sprouting in absence of injury Source: UniProtKB
  • defense response to Gram-negative bacterium Source: UniProtKB
  • defense response to Gram-positive bacterium Source: UniProtKB
  • dendrite development Source: UniProtKB
  • endocytosis Source: UniProtKB
  • extracellular matrix organization Source: UniProtKB
  • forebrain development Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: ARUK-UCL
  • innate immune response Source: UniProtKB
  • ionotropic glutamate receptor signaling pathway Source: UniProtKB
  • learning or memory Source: ARUK-UCL
  • lipoprotein metabolic process Source: ARUK-UCL
  • locomotory behavior Source: UniProtKB
  • mating behavior Source: UniProtKB
  • memory Source: ARUK-UCL
  • microglia development Source: ARUK-UCL
  • microglial cell activation Source: ARUK-UCL
  • modulation of age-related behavioral decline Source: ARUK-UCL
  • modulation of excitatory postsynaptic potential Source: ARUK-UCL
  • mRNA polyadenylation Source: UniProtKB
  • negative regulation of adenylate cyclase activity Source: ARUK-UCL
  • negative regulation of canonical Wnt signaling pathway Source: ARUK-UCL
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of gene expression Source: ARUK-UCL
  • negative regulation of long-term synaptic potentiation Source: ARUK-UCL
  • negative regulation of mitochondrion organization Source: ARUK-UCL
  • negative regulation of neuron death Source: ARUK-UCL
  • negative regulation of neuron differentiation Source: Ensembl
  • negative regulation of protein localization to nucleus Source: ARUK-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: ARUK-UCL
  • neuromuscular process controlling balance Source: Ensembl
  • neuron apoptotic process Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • neuron remodeling Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB-KW
  • platelet degranulation Source: Reactome
  • positive regulation of 1-phosphatidylinositol-3-kinase activity Source: ARUK-UCL
  • positive regulation of apoptotic process Source: ARUK-UCL
  • positive regulation of cAMP metabolic process Source: ARUK-UCL
  • positive regulation of cell activation Source: ARUK-UCL
  • positive regulation of cellular response to thapsigargin Source: ARUK-UCL
  • positive regulation of cellular response to tunicamycin Source: ARUK-UCL
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
  • positive regulation of cytosolic calcium ion concentration Source: ARUK-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: ARUK-UCL
  • positive regulation of excitatory postsynaptic potential Source: ARUK-UCL
  • positive regulation of G2/M transition of mitotic cell cycle Source: Ensembl
  • positive regulation of gene expression Source: ARUK-UCL
  • positive regulation of G-protein coupled receptor internalization Source: ARUK-UCL
  • positive regulation of G-protein coupled receptor protein signaling pathway Source: ARUK-UCL
  • positive regulation of JNK cascade Source: ARUK-UCL
  • positive regulation of long-term synaptic potentiation Source: ARUK-UCL
  • positive regulation of MAPK cascade Source: ARUK-UCL
  • positive regulation of membrane protein ectodomain proteolysis Source: ARUK-UCL
  • positive regulation of mitotic cell cycle Source: UniProtKB
  • positive regulation of monocyte chemotaxis Source: ARUK-UCL
  • positive regulation of neuron death Source: ARUK-UCL
  • positive regulation of neuron differentiation Source: ARUK-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCL
  • positive regulation of nitric oxide biosynthetic process Source: ARUK-UCL
  • positive regulation of oxidative stress-induced neuron death Source: ARUK-UCL
  • positive regulation of protein binding Source: ARUK-UCL
  • positive regulation of protein import Source: ARUK-UCL
  • positive regulation of protein kinase A signaling Source: ARUK-UCL
  • positive regulation of protein kinase B signaling Source: ARUK-UCL
  • positive regulation of protein metabolic process Source: ARUK-UCL
  • positive regulation of protein phosphorylation Source: ARUK-UCL
  • positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
  • positive regulation of receptor binding Source: ARUK-UCL
  • positive regulation of response to endoplasmic reticulum stress Source: ARUK-UCL
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: ARUK-UCL
  • positive regulation of superoxide anion generation Source: ARUK-UCL
  • positive regulation of tau-protein kinase activity Source: ARUK-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: ARUK-UCL
  • post-translational protein modification Source: Reactome
  • protein homooligomerization Source: ARUK-UCL
  • protein phosphorylation Source: UniProtKB
  • regulation of acetylcholine-gated cation channel activity Source: ARUK-UCL
  • regulation of dendritic spine maintenance Source: ARUK-UCL
  • regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • regulation of long-term neuronal synaptic plasticity Source: ARUK-UCL
  • regulation of multicellular organism growth Source: UniProtKB
  • regulation of NMDA receptor activity Source: ARUK-UCL
  • regulation of protein binding Source: Ensembl
  • regulation of response to calcium ion Source: ARUK-UCL
  • regulation of synapse structure or activity Source: UniProtKB
  • regulation of toll-like receptor signaling pathway Source: ARUK-UCL
  • regulation of translation Source: UniProtKB
  • response to lead ion Source: Ensembl
  • response to oxidative stress Source: Ensembl
  • response to yeast Source: UniProtKB
  • smooth endoplasmic reticulum calcium ion homeostasis Source: Ensembl
  • suckling behavior Source: Ensembl
  • synapse organization Source: ARUK-UCL
  • synaptic growth at neuromuscular junction Source: Ensembl
  • tumor necrosis factor production Source: ARUK-UCL
  • visual learning Source: UniProtKB

Keywordsi

Molecular functionHeparin-binding, Protease inhibitor, Serine protease inhibitor
Biological processApoptosis, Cell adhesion, Endocytosis, Notch signaling pathway
LigandCopper, Iron, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000142192-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3000178. ECM proteoglycans.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-416476. G alpha (q) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-432720. Lysosome Vesicle Biogenesis.
R-HSA-444473. Formyl peptide receptors bind formyl peptides and many other ligands.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-844456. The NLRP3 inflammasome.
R-HSA-879415. Advanced glycosylation endproduct receptor signaling.
R-HSA-8862803. Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
R-HSA-8957275. Post-translational protein phosphorylation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-977225. Amyloid fiber formation.
SABIO-RKiP05067.
SIGNORiP05067.

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid-beta A4 protein
Alternative name(s):
ABPP
APPI
Short name:
APP
Alzheimer disease amyloid protein
Amyloid precursor proteinCurated
Amyloid-beta precursor proteinCurated
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
Amyloid-beta protein 42
Short name:
Abeta42
Alternative name(s):
Beta-APP42
Amyloid-beta protein 40
Short name:
Abeta40
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
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000142192.20.
HGNCiHGNC:620. APP.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 699ExtracellularSequence analysisAdd BLAST682
Transmembranei700 – 723HelicalSequence analysisAdd BLAST24
Topological domaini724 – 770CytoplasmicSequence analysisAdd BLAST47

Keywords - Cellular componenti

Amyloid, Coated pit, Membrane

Pathology & Biotechi

Involvement in diseasei

Alzheimer disease 1 (AD1)26 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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 constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
See also OMIM:104300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000015670 – 671KM → NL in AD1. Corresponds to variant dbSNP:rs281865161Ensembl.2
Natural variantiVAR_044424678D → N in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750064Ensembl.1
Natural variantiVAR_000016692A → G in AD1; Flemish mutation; increases the solubility of processed amyloid-beta peptides and increases the stability of peptide oligomers. 3 PublicationsCorresponds to variant dbSNP:rs63750671Ensembl.1
Natural variantiVAR_014215693E → G in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63751039Ensembl.1
Natural variantiVAR_000019713A → T in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63750066Ensembl.1
Natural variantiVAR_032277714T → A in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750643Ensembl.1
Natural variantiVAR_014218714T → I in AD1; increased amyloid-beta protein 42/40 ratio. 2 PublicationsCorresponds to variant dbSNP:rs63750973Ensembl.1
Natural variantiVAR_010108715V → M in AD1; decreased amyloid-beta protein 40/total amyloid-beta. 1 PublicationCorresponds to variant dbSNP:rs63750734Ensembl.1
Natural variantiVAR_000020716I → V in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750399Ensembl.1
Natural variantiVAR_000023717V → F in AD1. 4 PublicationsCorresponds to variant dbSNP:rs63750264Ensembl.1
Natural variantiVAR_000022717V → G in AD1. 2 PublicationsCorresponds to variant dbSNP:rs63749964Ensembl.1
Natural variantiVAR_000021717V → I in AD1. 7 PublicationsCorresponds to variant dbSNP:rs63750264Ensembl.1
Natural variantiVAR_014219717V → L in AD1. 1 PublicationCorresponds to variant dbSNP:rs63750264Ensembl.1
Natural variantiVAR_010109723L → P in AD1. 1 PublicationCorresponds to variant dbSNP:rs63751122Ensembl.1
Cerebral amyloid angiopathy, APP-related (CAA-APP)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:605714
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014216693E → K in CAA-APP; Italian type. 1 PublicationCorresponds to variant dbSNP:rs63750579Ensembl.1
Natural variantiVAR_000017693E → Q in CAA-APP; Dutch type. 1 PublicationCorresponds to variant dbSNP:rs63750579Ensembl.1
Natural variantiVAR_014217694D → N in CAA-APP; Iowa type. 2 PublicationsCorresponds to variant dbSNP:rs63749810Ensembl.1
Natural variantiVAR_032276705L → V in CAA-APP; Italian type. 1 PublicationCorresponds to variant dbSNP:rs63750921Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi99 – 102KRGR → NQGG: Reduced heparin-binding. 1 Publication4
Mutagenesisi137H → N: Binds copper. Forms dimer. 1 Publication1
Mutagenesisi141M → T: Binds copper. Forms dimer. 1 Publication1
Mutagenesisi144C → S: Binds copper. No dimer formation. No copper reducing activity. 2 Publications1
Mutagenesisi147 – 149HLH → ALA: 50% decrease in copper reducing activity. 1 Publication3
Mutagenesisi147H → A: Some decrease in copper reducing activity. 2 Publications1
Mutagenesisi147H → N: Binds copper. Forms dimer. 2 Publications1
Mutagenesisi147H → Y: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications1
Mutagenesisi151H → K: Greatly reduced copper-mediated low-density lipoprotein oxidation. 2 Publications1
Mutagenesisi151H → N: Binds copper. Forms dimer. 2 Publications1
Mutagenesisi198S → A: Greatly reduced casein kinase phosphorylation. 2 Publications1
Mutagenesisi206S → A: Reduced casein kinase phosphorylation. 2 Publications1
Mutagenesisi499R → A: Reduced affinity for heparin; when associated with A-503. 1 Publication1
Mutagenesisi503K → A: Reduced affinity for heparin; when associated with A-499. 1 Publication1
Mutagenesisi656S → A: Abolishes chondroitin sulfate binding in L-APP733 isoform. 1 Publication1
Mutagenesisi676R → G: 60-70% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication1
Mutagenesisi681Y → F: 60-70% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication1
Mutagenesisi684H → R: Only 23% zinc-induced amyloid-beta protein 28 aggregation. 1 Publication1
Mutagenesisi704G → V: Reduced protein oxidation. No hippocampal neuron toxicity. 1
Mutagenesisi706M → L: Reduced lipid peroxidation inhibition. 2 Publications1
Mutagenesisi706M → V: No free radical production. No hippocampal neuron toxicity. 2 Publications1
Mutagenesisi717V → C or S: Unchanged amyloid-beta protein 42/total amyloid-beta ratio. 2 Publications1
Mutagenesisi717V → F, G or I: Increased amyloid-beta protein 42/40 ratio. 2 Publications1
Mutagenesisi717V → K: Decreased amyloid-beta protein 42/total amyloid-beta ratio. 2 Publications1
Mutagenesisi717V → M: Increased amyloid-beta protein 42/40 ratio. No change in apoptosis after caspase cleavage. 2 Publications1
Mutagenesisi728Y → A: No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in amyloid-beta protein 42 secretion. 3 Publications1
Mutagenesisi739D → A: No cleavage by caspases during apoptosis. 3 Publications1
Mutagenesisi739D → N: No effect on FADD-induced apoptosis. 3 Publications1
Mutagenesisi743T → A: Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension. 4 Publications1
Mutagenesisi743T → E: Reduced NGF-stimulated neurite extension. No effect on APP maturation. 4 Publications1
Mutagenesisi756G → A: APP internalization unchanged. No change in amyloid-beta protein 42 secretion. 1 Publication1
Mutagenesisi757Y → A: Little APP internalization. Reduced amyloid-beta protein 42 secretion. 4 Publications1
Mutagenesisi757Y → G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1. 4 Publications1
Mutagenesisi759N → A: No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced amyloid-beta protein 42 secretion. 2 Publications1
Mutagenesisi760P → A: Little APP internalization. Reduced amyloid-beta protein 42 secretion. 1 Publication1
Mutagenesisi762Y → A: Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in amyloid-beta protein 42 secretion. 2 Publications1

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi351.
GeneReviewsiAPP.
MalaCardsiAPP.
MIMi104300. phenotype.
605714. phenotype.
OpenTargetsiENSG00000142192.
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.

Chemistry databases

ChEMBLiCHEMBL2487.
DrugBankiDB05150. CAD106.
DB09148. Florbetaben (18F).
DB09149. Florbetapir (18F).
DB09151. Flutemetamol (18F).
DB02235. L-methionine (R)-S-oxide.
DB05846. Mito-4509.

Polymorphism and mutation databases

BioMutaiAPP.
DMDMi112927.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 173 PublicationsAdd BLAST17
ChainiPRO_000000008818 – 770Amyloid-beta A4 proteinAdd BLAST753
ChainiPRO_000000008918 – 687Soluble APP-alphaAdd BLAST670
ChainiPRO_000000009018 – 671Soluble APP-betaAdd BLAST654
ChainiPRO_000038196618 – 286N-APPAdd BLAST269
ChainiPRO_0000000091672 – 770C99Add BLAST99
ChainiPRO_0000000092672 – 713Amyloid-beta protein 42Add BLAST42
ChainiPRO_0000000093672 – 711Amyloid-beta protein 40Add BLAST40
ChainiPRO_0000000094688 – 770C83Add BLAST83
PeptideiPRO_0000000095688 – 713P3(42)Add BLAST26
PeptideiPRO_0000000096688 – 711P3(40)Add BLAST24
ChainiPRO_0000384574691 – 770C80Add BLAST80
ChainiPRO_0000000097712 – 770Gamma-secretase C-terminal fragment 59Add BLAST59
ChainiPRO_0000000098714 – 770Gamma-secretase C-terminal fragment 57Add BLAST57
ChainiPRO_0000000099721 – 770Gamma-secretase C-terminal fragment 50By similarityAdd BLAST50
ChainiPRO_0000000100740 – 770C31Add BLAST31

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi38 ↔ 62
Disulfide bondi73 ↔ 117
Disulfide bondi98 ↔ 105
Disulfide bondi133 ↔ 187
Disulfide bondi144 ↔ 174
Disulfide bondi158 ↔ 186
Modified residuei198Phosphoserine; by CK21 Publication1
Modified residuei206Phosphoserine; by CK11 Publication1
Disulfide bondi291 ↔ 341
Disulfide bondi300 ↔ 324
Disulfide bondi316 ↔ 337
Modified residuei441Phosphoserine; by FAM20C1 Publication1
Modified residuei497Phosphotyrosine1 Publication1
Glycosylationi542N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi571N-linked (GlcNAc...) asparagineCurated1
Glycosylationi633O-linked (GalNAc...) threonine; partial2 Publications1
Glycosylationi651O-linked (GalNAc...) threonine; partial2 Publications1
Glycosylationi652O-linked (GalNAc...) threonine; partial2 Publications1
Glycosylationi656O-linked (Xyl...) (chondroitin sulfate) serine; in L-APP isoforms1 Publication1
Glycosylationi659O-linked (HexNAc...) threonine; partial1 Publication1
Glycosylationi663O-linked (GalNAc...) threonine; partial1 Publication1 Publication1
Glycosylationi667O-linked (GalNAc...) serine; partial1 Publication1 Publication1
Glycosylationi681O-linked (HexNAc...) tyrosine; partial1 Publication1
Modified residuei729PhosphothreonineBy similarity1
Modified residuei730Phosphoserine; by APP-kinase IBy similarity1
Modified residuei743Phosphothreonine; by CDK5 and MAPK10Combined sources1 Publication1
Modified residuei757Phosphotyrosine1 Publication1
Cross-linki763Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)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 protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating 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 amyloid-beta peptides.
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 amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 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.3 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.6 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 amyloid-beta-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).
Amyloid-beta peptides are degraded by IDE.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei671 – 672Cleavage; by beta-secretase2
Sitei672 – 673Cleavage; by caspase-6; when associated with variant 670-N-L-6712
Sitei687 – 688Cleavage; by alpha-secretase2
Sitei690 – 691Cleavage; by theta-secretase1 Publication2
Sitei711 – 712Cleavage; by gamma-secretase; site 12
Sitei713 – 714Cleavage; by gamma-secretase; site 22
Sitei720 – 721Cleavage; by gamma-secretase; site 32
Sitei739 – 740Cleavage; by caspase-6, caspase-8 or caspase-92

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Oxidation, Phosphoprotein, Proteoglycan, Ubl conjugation

Proteomic databases

EPDiP05067.
MaxQBiP05067.
PaxDbiP05067.
PeptideAtlasiP05067.
PRIDEiP05067.

2D gel databases

SWISS-2DPAGEiP05067.

PTM databases

iPTMnetiP05067.
PhosphoSitePlusiP05067.
SwissPalmiP05067.
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

BgeeiENSG00000142192.
ExpressionAtlasiP05067. baseline and differential.
GenevisibleiP05067. HS.

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 protein 42 binds CHRNA7 in hippocampal neurons. Amyloid-beta 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. Amyloid-beta protein 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. Interacts with SORL1. Interacts with PLD3. Interacts with VDAC1 (PubMed:25168729).By similarity32 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • acetylcholine receptor binding Source: UniProtKB
  • apolipoprotein binding Source: ARUK-UCL
  • chaperone binding Source: ARUK-UCL
  • enzyme binding Source: ParkinsonsUK-UCL
  • ephrin receptor binding Source: ARUK-UCL
  • frizzled binding Source: ARUK-UCL
  • growth factor receptor binding Source: Ensembl
  • heparan sulfate proteoglycan binding Source: ARUK-UCL
  • identical protein binding Source: IntAct
  • low-density lipoprotein particle receptor binding Source: ARUK-UCL
  • protein dimerization activity Source: ARUK-UCL
  • protein heterodimerization activity Source: ARUK-UCL
  • protein homodimerization activity Source: ARUK-UCL
  • PTB domain binding Source: BHF-UCL
  • receptor binding Source: ARUK-UCL

Protein-protein interaction databases

BioGridi106848. 2112 interactors.
CORUMiP05067.
DIPiDIP-574N.
ELMiP05067.
IntActiP05067. 133 interactors.
MINTiMINT-150767.
STRINGi9606.ENSP00000284981.

Chemistry databases

BindingDBiP05067.

Structurei

Secondary structure

1770
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi26 – 28Combined sources3
Beta strandi33 – 35Combined sources3
Beta strandi43 – 45Combined sources3
Turni47 – 49Combined sources3
Beta strandi52 – 54Combined sources3
Beta strandi56 – 58Combined sources3
Helixi66 – 76Combined sources11
Beta strandi82 – 87Combined sources6
Beta strandi92 – 94Combined sources3
Beta strandi97 – 99Combined sources3
Turni100 – 102Combined sources3
Beta strandi103 – 106Combined sources4
Beta strandi110 – 112Combined sources3
Beta strandi115 – 119Combined sources5
Beta strandi134 – 139Combined sources6
Helixi147 – 160Combined sources14
Beta strandi163 – 174Combined sources12
Turni175 – 177Combined sources3
Beta strandi178 – 188Combined sources11
Helixi288 – 292Combined sources5
Beta strandi299 – 301Combined sources3
Beta strandi304 – 310Combined sources7
Turni311 – 314Combined sources4
Beta strandi315 – 321Combined sources7
Beta strandi323 – 325Combined sources3
Beta strandi331 – 333Combined sources3
Helixi334 – 341Combined sources8
Helixi374 – 380Combined sources7
Helixi389 – 418Combined sources30
Beta strandi421 – 423Combined sources3
Helixi425 – 480Combined sources56
Beta strandi482 – 484Combined sources3
Helixi487 – 518Combined sources32
Helixi520 – 546Combined sources27
Helixi547 – 550Combined sources4
Helixi552 – 566Combined sources15
Helixi615 – 618Combined sources4
Beta strandi620 – 622Combined sources3
Helixi673 – 675Combined sources3
Beta strandi676 – 678Combined sources3
Beta strandi679 – 682Combined sources4
Beta strandi683 – 685Combined sources3
Beta strandi688 – 691Combined sources4
Beta strandi692 – 694Combined sources3
Turni695 – 698Combined sources4
Beta strandi702 – 705Combined sources4
Beta strandi707 – 712Combined sources6
Helixi744 – 754Combined sources11
Beta strandi755 – 758Combined sources4
Beta strandi763 – 765Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
2MGTNMR-A/B672-687[»]
2MJ1NMR-A688-705[»]
2MPZNMR-A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a686-711[»]
2MVXNMR-A/B/C/D/E/F/G/H/I/J672-711[»]
2MXUNMR-A/B/C/D/E/F/G/H/I/J/K/L672-713[»]
2NAONMR-A/B/C/D/E/F672-713[»]
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[»]
3BAEX-ray1.59A672-699[»]
3BKJX-ray1.59A672-687[»]
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[»]
3JQ5X-ray2.03B672-679[»]
3JQLX-ray1.20B687-692[»]
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[»]
4JFNX-ray1.75A23-185[»]
4M1CX-ray3.50G/H672-711[»]
4MDRX-ray1.85B758-767[»]
4MVIX-ray1.70B672-711[»]
4MVKX-ray1.50B689-694[»]
4MVLX-ray2.30E/F/G/H672-711[»]
4NGEX-ray2.70B/E672-711[»]
4OJFX-ray2.00A672-679[»]
4ONFX-ray2.00P672-678[»]
4ONGX-ray2.20P672-711[»]
4PQDX-ray1.33A22-126[»]
4PWQX-ray1.40A/B18-190[»]
4XXDX-ray2.41C/F683-699[»]
5AEFelectron microscopy5.00A/B686-713[»]
5AM8X-ray1.90P/Q/R/S675-681[»]
5AMBX-ray1.55P/Q706-713[»]
5BUOX-ray2.31A/B370-710[»]
5C67X-ray1.83C/E294-344[»]
5CSZX-ray1.80D/E672-682[»]
5HOWX-ray2.29A/B/C/D/E/F688-705[»]
5HOXX-ray1.90A/B/C/D/E/F688-707[»]
5HOYX-ray2.29A/B/C/D/E/F688-707[»]
5KK3NMR-A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R672-713[»]
5KNAX-ray2.32A682-696[»]
ProteinModelPortaliP05067.
SMRiP05067.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05067.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini291 – 341BPTI/Kunitz inhibitorPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni96 – 110Heparin-bindingAdd BLAST15
Regioni181 – 188Zinc-binding8
Regioni391 – 423Heparin-bindingAdd BLAST33
Regioni491 – 522Heparin-bindingAdd BLAST32
Regioni523 – 540Collagen-bindingAdd BLAST18
Regioni732 – 751Interaction with G(o)-alphaAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi724 – 734Basolateral sorting signalAdd BLAST11
Motifi759 – 762NPXY motif; contains endocytosis signal4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi230 – 260Asp/Glu-rich (acidic)Add BLAST31
Compositional biasi274 – 280Poly-Thr7

Domaini

The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.1 Publication
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.1 Publication

Sequence similaritiesi

Belongs to the APP family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3540. Eukaryota.
ENOG410ZW2A. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000232190.
HOVERGENiHBG000051.
InParanoidiP05067.
KOiK04520.
OMAiREVCSEQ.
OrthoDBiEOG091G0UW4.
PhylomeDBiP05067.
TreeFamiTF317274.

Family and domain databases

CDDicd00109. KU. 1 hit.
Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.230.10. 1 hit.
4.10.410.10. 1 hit.
InterProiView protein in InterPro
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. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
PANTHERiPTHR23103:SF17. PTHR23103:SF17. 1 hit.
PfamiView protein in Pfam
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.
PRINTSiPR00203. AMYLOIDA4.
PR00759. BASICPTASE.
PR00204. BETAAMYLOID.
SMARTiView protein in SMART
SM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.