App
entrez
54226
canonical
uniprot
P08592
canonical
ensembl
ENSRNOG00000006997
resolver
ensembl
ENSRNOG00055002269
resolver
ensembl
ENSRNOG00060016739
resolver
ensembl
ENSRNOG00065006297
resolver
ensp
ENSRNOP00000040243
resolver
ensp
ENSRNOP00000041613
resolver
ensp
ENSRNOP00000078198
resolver
ensp
ENSRNOP00000111736
resolver
enst
ENSRNOT00000044081
resolver
enst
ENSRNOT00000104573
resolver
genesymbol
App
resolver
genesymbol_syn
A4
resolver
genesymbol_syn
AD1
resolver
uniprot
A0A0H2UHW9
resolver
uniprot
A0A8I5Y8G9
resolver
uniprot
A0ACM8Q3G1
resolver
uniprot
Q547B7
resolver
uniprot
Q6P6Q5
resolver
uniprot_entry
A0A0H2UHW9_RAT
resolver
uniprot_entry
A0ACM8Q3G1_RAT
resolver
uniprot_entry
A4_RAT
resolver
uniprot_entry
Q6P6Q5_RAT
resolver
uniprot_sec
A0A8I5Y8G9
resolver
uniprot_sec
Q547B7
resolver
amino_acid_sequence
MLPSLALLLLAAWTVRALEVPTDGNAGLLAEPQIAMFCGKLNMHMNVQNGKWESDPSGTKTCIGTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHTHIVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDSIDSADAEEDDSDVWWGGADTDYADGGEDKVVEVAEEEEVADVEEEEAEDDEDVEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSVSSQSLLKTTSEPLPQDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPHHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHPFGVDSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFGHDSGFEVRHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
uniprot
proteins
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. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity). Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity). Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o)-alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). 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 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 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P05067}.; FUNCTION: Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse amyloid-beta peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Amyloid-beta protein 42 may activate mononuclear phagocytes in the brain and elicits inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also binds GPC1 in lipid rafts (By similarity). {ECO:0000250}.; FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. {ECO:0000250}.
uniprot
proteins
mass_dalton
86704
uniprot
proteins
mutagenesis
MUTAGEN 656; /note="S->A: No chondroitin sulfate linkage to isoform L-APP733."; /evidence="ECO:0000269|PubMed:7737970"; MUTAGEN 704; /note="G->V: Little oxidized neuronal proteins. Scarce amyloid-beta protein 42 aggregation. No neurotoxicity."; /evidence="ECO:0000269|PubMed:11959460"; MUTAGEN 732..733; /note="HH->GL,GP: Almost complete loss of binding to GNAO1. No inhibition of GTPase activity."; /evidence="ECO:0000269|PubMed:10024358"; MUTAGEN 743; /note="T->A: No effect on neurite growth and maturation."; /evidence="ECO:0000269|PubMed:10341243"; MUTAGEN 743; /note="T->E: Inhibits neurite growth and maturation."; /evidence="ECO:0000269|PubMed:10341243"; MUTAGEN 757; /note="Y->G: No DBB1 binding."; /evidence="ECO:0000269|PubMed:9930726"; MUTAGEN 759; /note="N->A: Some DBB1 binding."; /evidence="ECO:0000269|PubMed:9930726"; MUTAGEN 762; /note="Y->A: Some DBB1 binding."; /evidence="ECO:0000269|PubMed:9930726"; MUTAGEN 763; /note="K->R: Loss of ubiquitination."; /evidence="ECO:0000269|PubMed:22847417
uniprot
proteins
post_translational_modification
PTM: 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). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro). Amyloid-beta protein 40 and Amyloid-beta protein 42 are cleaved by ACE. 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. {ECO:0000250|UniProtKB:P05067}.; PTM: Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-3, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides. {ECO:0000250}.; PTM: N-glycosylated. {ECO:0000250|UniProtKB:P05067}.; PTM: O-glycosylated. O-linkage of chondroitin sulfate to the L-APP isoforms produces the APP proteoglycan core proteins, the appicans. The chondroitin sulfate chain of appicans contains 4-O-sulfated galactose in the linkage region and chondroitin sulfate E in the repeated disaccharide region. {ECO:0000269|PubMed:11479316}.; PTM: Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (PubMed:10329382, PubMed:10341243, PubMed:9085254). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (PubMed:10341243). 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 (PubMed:10936190). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (By similarity). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (By similarity). Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP (By similarity). This phosphorylation is inhibited by heparin (By similarity). {ECO:0000250|UniProtKB:P05067, ECO:0000269|PubMed:10329382, ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:10936190, ECO:0000269|PubMed:9085254}.; PTM: Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. {ECO:0000250}.; PTM: 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). {ECO:0000250}.; PTM: Amyloid-beta peptides are degraded by IDE. {ECO:0000250|UniProtKB:P12023}.; PTM: Sulfated on tyrosine residues. {ECO:0000250|UniProtKB:P05067}.
uniprot
proteins
protein_family
APP family
uniprot
proteins
pubmed
10024358
uniprot
proteins
pubmed
10329382
uniprot
proteins
pubmed
10341243
uniprot
proteins
pubmed
10386999
uniprot
proteins
pubmed
10413512
uniprot
proteins
pubmed
10936190
uniprot
proteins
pubmed
11479316
uniprot
proteins
pubmed
11483588
uniprot
proteins
pubmed
11959460
uniprot
proteins
pubmed
1673681
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
22847417
uniprot
proteins
pubmed
23011729
uniprot
proteins
pubmed
26479776
uniprot
proteins
pubmed
2648331
uniprot
proteins
pubmed
2900758
uniprot
proteins
pubmed
2968652
uniprot
proteins
pubmed
7737970
uniprot
proteins
pubmed
7744833
uniprot
proteins
pubmed
7913895
uniprot
proteins
pubmed
8624099
uniprot
proteins
pubmed
8996834
uniprot
proteins
pubmed
9085254
uniprot
proteins
pubmed
9930726
uniprot
proteins
sequence_length
770
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P05067}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P05067}. Membrane {ECO:0000250|UniProtKB:P05067}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P05067}. Perikaryon {ECO:0000269|PubMed:10341243}. Cell projection, growth cone {ECO:0000269|PubMed:10341243}. Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:P05067}. Early endosome {ECO:0000250|UniProtKB:P05067}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:P05067}. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles. 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. APP sorts to the basolateral surface in epithelial cells (By similarity). During neuronal differentiation, the Thr-742 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body (PubMed:10341243). 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 (By similarity). {ECO:0000250|UniProtKB:P05067, ECO:0000269|PubMed:10341243}.; SUBCELLULAR LOCATION: [C83]: Endoplasmic reticulum {ECO:0000250|UniProtKB:P05067}. Golgi apparatus {ECO:0000250|UniProtKB:P05067}. Early endosome {ECO:0000250|UniProtKB:P05067}.; SUBCELLULAR LOCATION: [C99]: Early endosome {ECO:0000250|UniProtKB:P05067}.; SUBCELLULAR LOCATION: [Amyloid-beta protein 42]: Cell surface. Note=Associates with FPR2 at the cell surface and the complex is then rapidly internalized. {ECO:0000250|UniProtKB:P05067}.; SUBCELLULAR LOCATION: [Gamma-secretase C-terminal fragment 59]: Nucleus. Cytoplasm. Note=Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65) (By similarity). In dopaminergic neurons, the phosphorylated Thr-743 form is localized to the nucleus (By similarity). {ECO:0000250|UniProtKB:P05067, ECO:0000250|UniProtKB:P12023}.; SUBCELLULAR LOCATION: [Soluble APP-beta]: Secreted {ECO:0000250|UniProtKB:P05067}.
uniprot
proteins
transmembrane_region
TRANSMEM 702..722; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P05067
uniprot
proteins