Names & Taxonomy
- Uniprot ID:
- P05067
- Entry Name:
- A4_HUMAN
- Status:
- reviewed
- Protein Names:
- Amyloid beta A4 protein (ABPP) (APPI) (APP) (Alzheimer disease amyloid protein) (Amyloid precursor protein) (Beta-amyloid precursor protein) (Cerebral vascular amyloid peptide) (CVAP) (PreA4) (Protease nexin-II) (PN-II) [Cleaved into: N-APP; Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99; Beta-amyloid protein 42 (Beta-APP42); Beta-amyloid protein 40 (Beta-APP40); C83; P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59 (Amyloid intracellular domain 59) (AICD-59) (AID(59)) (Gamma-CTF(59)); Gamma-secretase C-terminal fragment 57 (Amyloid intracellular domain 57) (AICD-57) (AID(57)) (Gamma-CTF(57)); Gamma-secretase C-terminal fragment 50 (Amyloid intracellular domain 50) (AICD-50) (AID(50)) (Gamma-CTF(50)); C31]
- Gene Names:
- APP A4 AD1
- Gene Names Primary:
- APP
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 770
- Sequence:
- MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Membrane; Single-pass type I membrane protein. Membrane, clathrin-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.
Function
- Function:
- 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 Cu(2+)-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 Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.
- Gene Ontology Go:
- apical part of cell
astrocyte projection
axon
cell surface
cell-cell junction
ciliary rootlet
coated pit
cytoplasm
cytosol
dendritic shaft
dendritic spine
endosome
endosome lumen
ER to Golgi transport vesicle
extracellular exosome
extracellular region
extracellular space
Golgi apparatus
growth cone filopodium
growth cone lamellipodium
integral component of membrane
integral component of plasma membrane
intracellular membrane-bounded organelle
main axon
membrane raft
neuromuscular junction
nuclear envelope lumen
perinuclear region of cytoplasm
plasma membrane
platelet alpha granule lumen
receptor complex
rough endoplasmic reticulum
smooth endoplasmic reticulum
spindle midzone
synapse
terminal bouton
trans-Golgi network membrane
acetylcholine receptor binding
DNA binding
enzyme binding
heparin binding
identical protein binding
peptidase activator activity
PTB domain binding
receptor binding
serine-type endopeptidase inhibitor activity
transition metal ion binding
adult locomotory behavior
amyloid fibril formation
antibacterial humoral response
antifungal humoral response
axo-dendritic transport
axon midline choice point recognition
axonogenesis
blood coagulation
cell adhesion
cellular copper ion homeostasis
cellular process
cellular protein metabolic process
cellular response to cAMP
cellular response to nerve growth factor stimulus
cellular response to norepinephrine stimulus
cholesterol metabolic process
collateral sprouting in absence of injury
defense response to Gram-negative bacterium
defense response to Gram-positive bacterium
dendrite development
endocytosis
extracellular matrix organization
forebrain development
innate immune response
ionotropic glutamate receptor signaling pathway
locomotory behavior
mating behavior
membrane organization
mRNA polyadenylation
negative regulation of endopeptidase activity
negative regulation of neuron differentiation
neuromuscular process controlling balance
neuron apoptotic process
neuron projection development
neuron remodeling
Notch signaling pathway
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
platelet activation
platelet degranulation
positive regulation of G2/M transition of mitotic cell cycle
positive regulation of mitotic cell cycle
positive regulation of transcription from RNA polymerase II promoter
post-Golgi vesicle-mediated transport
protein phosphorylation
regulation of epidermal growth factor-activated receptor activity
regulation of multicellular organism growth
regulation of protein binding
regulation of synapse structure or activity
regulation of translation
response to lead ion
response to oxidative stress
response to yeast
smooth endoplasmic reticulum calcium ion homeostasis
suckling behavior
synaptic growth at neuromuscular junction
visual learning - Gene Ontology Biological Process:
- adult locomotory behavior
amyloid fibril formation
antibacterial humoral response
antifungal humoral response
axo-dendritic transport
axon midline choice point recognition
axonogenesis
blood coagulation
cell adhesion
cellular copper ion homeostasis
cellular process
cellular protein metabolic process
cellular response to cAMP
cellular response to nerve growth factor stimulus
cellular response to norepinephrine stimulus
cholesterol metabolic process
collateral sprouting in absence of injury
defense response to Gram-negative bacterium
defense response to Gram-positive bacterium
dendrite development
endocytosis
extracellular matrix organization
forebrain development
innate immune response
ionotropic glutamate receptor signaling pathway
locomotory behavior
mating behavior
membrane organization
mRNA polyadenylation
negative regulation of endopeptidase activity
negative regulation of neuron differentiation
neuromuscular process controlling balance
neuron apoptotic process
neuron projection development
neuron remodeling
Notch signaling pathway
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
platelet activation
platelet degranulation
positive regulation of G2/M transition of mitotic cell cycle
positive regulation of mitotic cell cycle
positive regulation of transcription from RNA polymerase II promoter
post-Golgi vesicle-mediated transport
protein phosphorylation
regulation of epidermal growth factor-activated receptor activity
regulation of multicellular organism growth
regulation of protein binding
regulation of synapse structure or activity
regulation of translation
response to lead ion
response to oxidative stress
response to yeast
smooth endoplasmic reticulum calcium ion homeostasis
suckling behavior
synaptic growth at neuromuscular junction
visual learning - Gene Ontology Molecular Function:
- acetylcholine receptor binding
DNA binding
enzyme binding
heparin binding
identical protein binding
peptidase activator activity
PTB domain binding
receptor binding
serine-type endopeptidase inhibitor activity
transition metal ion binding - Gene Ontology Cellular Component:
- apical part of cell
astrocyte projection
axon
cell-cell junction
cell surface
ciliary rootlet
coated pit
cytoplasm
cytosol
dendritic shaft
dendritic spine
endosome
endosome lumen
ER to Golgi transport vesicle
extracellular exosome
extracellular region
extracellular space
Golgi apparatus
growth cone filopodium
growth cone lamellipodium
integral component of membrane
integral component of plasma membrane
intracellular membrane-bounded organelle
main axon
membrane raft
neuromuscular junction
nuclear envelope lumen
perinuclear region of cytoplasm
plasma membrane
platelet alpha granule lumen
receptor complex
rough endoplasmic reticulum
smooth endoplasmic reticulum
spindle midzone
synapse
terminal bouton
trans-Golgi network membrane - Keywords:
- 3D-structure
Alternative splicing
Alzheimer disease
Amyloid
Amyloidosis
Apoptosis
Cell adhesion
Coated pit
Complete proteome
Copper
Direct protein sequencing
Disease mutation
Disulfide bond
Endocytosis
Glycoprotein
Heparin-binding
Iron
Isopeptide bond
Membrane
Metal-binding
Neurodegeneration
Notch signaling pathway
Oxidation
Phosphoprotein
Polymorphism
Protease inhibitor
Proteoglycan
Reference proteome
Serine protease inhibitor
Signal
Transmembrane
Transmembrane helix
Ubl conjugation
Zinc - Interacts With:
- Itself; Q306T3; P31696; Q02410; O00213; Q92870; P51693; Q06481; P02647; Q13867; P15253; P27797; Q8K3H7; P39060; P07339; O75955; P01100; P46089; Q9NSC5; Q99714; O43736; P05412; Q99683; P10636; Q93074; P03897; P07196; P21359; P08138; P07174; P61457; Q15113; P30101; Q13526; P04156; P49768; P29353; Q92529; Q9NP59; Q8BGY9; Q9HCB6; P01137; P61812; O75509; Q13625
Publication
- PubMed ID:
- 2881207 2893289 2783775 2110105 1587857 9108164 12859342 14702039 10830953 15489334 3140222 2538123 3597385 12665801 2893290 2893291 2893379 8576160 8476439 2675837 15201367 8248178 1406936 8109908 8229004 3312495 3810169 2949367 22576872 16816112 2569763 3035574 7737970 9168929 11775062 2506449 1969731 8344894 8446172 7913895 8158260 8886002 8626687 8887653 8855266 9357988 9338779 9843960 10413512 10535332 9890987 10383380 10461923 10816430 10681545 12214090 11689470 11278849 11274207 11438549 11544248 11238726 11943163 11724784 11784781 12032279 15084524 15347684 8131745 8999878 9585534 10319819 10341243 10806211 10742146 11517218 11146006 11851430 11877420 16335952 2900137 12142279 16174740 18468999 19366692 19225519 19901339 20811458 21269460 21712440 22457725 24275569 24336208 25168729 26091039 2125487 1718421 7516706 7588758 8973180 9300481 9693002 10201399 10821838 10940221 10940222 15304215 17051221 17909280 17239395 17895381 19923222 20212142 1363811 2111584 1671712 1908231 1678058 1944558 1925564 1415269 1303239 1302033 1307241 1303275 8267572 8154870 8290042 8577393 9328472 9754958 10097173 10631141 10665499 10867787 11063718 11409420 11311152 11528419 12034808 12654973 15365148 16178030 15668448 20697050