App
entrez
11820
canonical
uniprot
P12023
canonical
ensembl
ENSMUSG00000022892
resolver
ensp
ENSMUSP00000005406
resolver
ensp
ENSMUSP00000153907
resolver
ensp
ENSMUSP00000154061
resolver
ensp
ENSMUSP00000154097
resolver
ensp
ENSMUSP00000154389
resolver
ensp
ENSMUSP00000154401
resolver
ensp
ENSMUSP00000229092
resolver
enst
ENSMUST00000226232
resolver
enst
ENSMUST00000226801
resolver
enst
ENSMUST00000227021
resolver
genesymbol
App
resolver
genesymbol_syn
A4
resolver
genesymbol_syn
AD1
resolver
uniprot
A0A2I3BPT1
resolver
uniprot
A0A2I3BQJ4
resolver
uniprot
A0A2I3BQZ9
resolver
uniprot
P97487
resolver
uniprot
P97942
resolver
uniprot
Q3TWF3
resolver
uniprot
Q6GR78
resolver
uniprot
Q99K32
resolver
uniprot_entry
A0A2I3BPT1_MOUSE
resolver
uniprot_entry
A0A2I3BQJ4_MOUSE
resolver
uniprot_entry
A0A2I3BQZ9_MOUSE
resolver
uniprot_entry
A4_MOUSE
resolver
uniprot_entry
Q3TWF3_MOUSE
resolver
uniprot_entry
Q6GR78_MOUSE
resolver
uniprot_sec
P97487
resolver
uniprot_sec
P97942
resolver
uniprot_sec
Q99K32
resolver
amino_acid_sequence
MLPSLALLLLAAWTVRALEVPTDGNAGLLAEPQIAMFCGKLNMHMNVQNGKWESDPSGTKTCIGTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHTHIVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDSVDSADAEEDDSDVWWGGADTDYADGGEDKVVEVAEEEEVADVEEEEADDDEDVEDGDEVEEEAEEPYEEATERTTSTATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCVPFFYGGCGGNRNNFDTEEYCMAVCGSVSTQSLLKTTSEPLPQDPDKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPHHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHPFGVDSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFGHDSGFEVRHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
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. Can promote transcription activation through binding to APBB1-KAT5 and inhibit 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 (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 cortical neurons (By similarity). 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. {ECO:0000250, ECO:0000250|UniProtKB:P05067, ECO:0000269|PubMed:15677459}.; 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 elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also binds GPC1 in lipid rafts (By similarity). {ECO:0000250}.; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. {ECO:0000269|PubMed:15677459}.
uniprot
proteins
mass_dalton
86722
uniprot
proteins
mutagenesis
MUTAGEN 728; /note="Y->A: No effect on MAPK8IP1 binding."; /evidence="ECO:0000269|PubMed:11517249"; MUTAGEN 732..733; /note="HH->GL,GP: Almost complete loss of binding to G(o) alpha subunit. No inhibition of GTPase activity."; MUTAGEN 743; /note="T->E: No effect on MAPK8IP1 binding."; /evidence="ECO:0000269|PubMed:11517249"; MUTAGEN 756; /note="G->F,H,N,S,W: Greatly impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302"; MUTAGEN 756; /note="G->Y: Impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302"; MUTAGEN 757; /note="Y->F: Greatly promotes interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 757; /note="Y->G,H,V: Greatly impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 757; /note="Y->G: No MAPK8IP1 nor APBA1 nor APBB1 nor DAB1 binding."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 757; /note="Y->I,W: Impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 759; /note="N->A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 759; /note="N->G,L,M,P: Greatly impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 760; /note="P->E,F,I,K,L,Q,R,V,W,Y: Greatly impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302"; MUTAGEN 762; /note="Y->A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249"; MUTAGEN 762; /note="Y->W: Greatly impairs interaction with DAB2."; /evidence="ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11517249
uniprot
proteins
post_translational_modification
PTM: Proteolytically processed under normal cellular conditions (PubMed:11553691, PubMed:23931995). 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 (PubMed:11553691, PubMed:23931995). 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 (By similarity). {ECO:0000250|UniProtKB:P05067, ECO:0000269|PubMed:11553691, ECO:0000269|PubMed:23931995}.; PTM: Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides. {ECO:0000250|UniProtKB:P05067}.; PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P05067}.; PTM: Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (By similarity). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (By similarity). 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 (By similarity). 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 (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (By similarity). 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:28720718}.; 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:0000269|PubMed:12634421}.; PTM: Sulfated on tyrosine residues. {ECO:0000250|UniProtKB:P05067}.
uniprot
proteins
protein_family
APP family
uniprot
proteins
pubmed
11144355
uniprot
proteins
pubmed
11235921
uniprot
proteins
pubmed
11247302
uniprot
proteins
pubmed
11279131
uniprot
proteins
pubmed
11517249
uniprot
proteins
pubmed
11553691
uniprot
proteins
pubmed
11912189
uniprot
proteins
pubmed
12011466
uniprot
proteins
pubmed
12634421
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1555768
uniprot
proteins
pubmed
15677459
uniprot
proteins
pubmed
16174740
uniprot
proteins
pubmed
16314516
uniprot
proteins
pubmed
16407538
uniprot
proteins
pubmed
1756177
uniprot
proteins
pubmed
18650440
uniprot
proteins
pubmed
21084623
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23931995
uniprot
proteins
pubmed
2493250
uniprot
proteins
pubmed
25168729
uniprot
proteins
pubmed
25592972
uniprot
proteins
pubmed
2569710
uniprot
proteins
pubmed
25757569
uniprot
proteins
pubmed
26260791
uniprot
proteins
pubmed
28720718
uniprot
proteins
pubmed
30429473
uniprot
proteins
pubmed
3322280
uniprot
proteins
pubmed
8510506
uniprot
proteins
sequence_length
770
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26260791}; 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:0000250|UniProtKB:P08592}. Cell projection, growth cone {ECO:0000250|UniProtKB:P08592}. Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:P05067}. Early endosome {ECO:0000269|PubMed:25592972, ECO:0000269|PubMed:26260791}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:P05067}. Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:23931995}. 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. 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 (By similarity). Associates with GPC1 in perinuclear compartments (PubMed:15677459). Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions (By similarity). Upon neuronal activation, routed into BACE1-positive recycling endosomes via a clathrin -dependent mechanism (PubMed:23931995). {ECO:0000250|UniProtKB:P05067, ECO:0000269|PubMed:15677459, ECO:0000269|PubMed:23931995}.; SUBCELLULAR LOCATION: [C99]: Early endosome {ECO:0000250|UniProtKB:P05067}.; SUBCELLULAR LOCATION: [C83]: Endoplasmic reticulum {ECO:0000250|UniProtKB:P05067}. Golgi apparatus {ECO:0000250|UniProtKB:P05067}. Early endosome {ECO:0000250|UniProtKB:P05067}.; SUBCELLULAR LOCATION: [Soluble APP-beta]: Secreted {ECO:0000305}.; 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 {ECO:0000269|PubMed:28720718}. Cytoplasm {ECO:0000250|UniProtKB:P05067}. 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 (PubMed:28720718). {ECO:0000250|UniProtKB:P05067, ECO:0000269|PubMed:28720718}.
uniprot
proteins
transmembrane_region
TRANSMEM 702..722; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P05067
uniprot
proteins