Protein: Amyloid-beta precursor protein (ABPP) (APP) (Alzheimer disease amyloid A4 protein homolog) (Alzheimer disease amyloid protein) (Amyloid precursor protein) (Amyloid-beta (A4) precursor protein) (Amyloid-beta A4 protein) (Amyloidogenic glycoprotein) (AG) [Cleaved into: N-APP; Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99 (APP-C99) (Beta-secretase C-terminal fragment) (Beta-CTF); Amyloid-beta protein 42 (Abeta42) (Beta-APP42); Amyloid-beta protein 40 (Abeta40) (Beta-APP40); C83 (Alpha-secretase C-terminal fragment) (Alpha-CTF); P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59 (APP-C59) (Amyloid intracellular domain 59) (AID(59)) (Gamma-CTF(59)); Gamma-secretase C-terminal fragment 57 (APP-C57) (Amyloid intracellular domain 57) (AID(57)) (Gamma-CTF(57)); Gamma-secretase C-terminal fragment 50 (Amyloid intracellular domain 50) (AID(50)) (Gamma-CTF(50)); C31] (P12023)
Organism: Mus musculus (Mouse)
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 synapes 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.
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}.
Interaction partners:
- Amyloid beta precursor protein binding family B member 1
- Tumor necrosis factor receptor superfamily member 21
- Beta-secretase 1
- Amyloid-beta A4 precursor protein-binding family A member 2
- Presenilin-1
- Apolipoprotein E
- Sortilin-related receptor
- Major prion protein
- Amyloid beta precursor protein binding family B member 2
- Clusterin
Sequence:
MLPSLALLLLAAWTVRALEVPTDGNAGLLAEPQIAMFCGKLNMHMNVQNGKWESDPSGTKTCIGTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHTHIVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDSVDSADAEEDDSDVWWGGADTDYADGGEDKVVEVAEEEEVADVEEEEADDDEDVEDGDEVEEEAEEPYEEATERTTSTATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCVPFFYGGCGGNRNNFDTEEYCMAVCGSVSTQSLLKTTSEPLPQDPDKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPHHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHPFGVDSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFGHDSGFEVRHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN