Amyloid-beta A4 protein (P12023)

Uniprot ID P12023
Protein Name Amyloid-beta A4 protein
Gene Name App
Species Mus musculus (Mouse)
Signal peptide(a) Y Secretome P(b) 0.205
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 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. 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. .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}.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. {ECO:0000269|PubMed:15677459}.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). {ECO:0000250}.
GO - Molecular function
  • DNA binding : IDA:MGI
  • enzyme binding : ISO:MGI
  • growth factor receptor binding : ISO:MGI
  • heparin binding : IEA:UniProtKB-KW
  • identical protein binding : ISO:MGI
  • low-density lipoprotein particle receptor binding : IPI:ARUK-UCL
  • peptidase activator activity : ISO:MGI
  • PTB domain binding : ISO:MGI
  • serine-type endopeptidase inhibitor activity : ISO:MGI
  • signaling receptor binding : ISO:MGI
  • transition metal ion binding : IEA:InterPro
GO - Biological process
  • adult locomotory behavior : IMP:MGI
  • amyloid fibril formation : ISO:MGI
  • astrocyte activation : ISO:MGI
  • astrocyte activation involved in immune response : ISO:MGI
  • axo-dendritic transport : IMP:MGI
  • axon midline choice point recognition : IMP:MGI
  • axonogenesis : IMP:MGI
  • cell adhesion : IEA:UniProtKB-KW
  • cellular copper ion homeostasis : IMP:MGI
  • cellular process : ISO:MGI
  • cellular response to amyloid-beta : ISO:MGI
  • cellular response to cAMP : IEA:Ensembl
  • cellular response to nerve growth factor stimulus : IEA:Ensembl
  • cellular response to norepinephrine stimulus : ISO:MGI
  • cholesterol metabolic process : IMP:MGI
  • collateral sprouting in absence of injury : IGI:MGI
  • dendrite development : IMP:MGI
  • endocytosis : IMP:MGI
  • extracellular matrix organization : IGI:MGI
  • forebrain development : IMP:MGI
  • ionotropic glutamate receptor signaling pathway : IMP:MGI
  • learning : ISO:MGI
  • learning or memory : ISO:MGI
  • locomotory behavior : IGI:MGI
  • long-term synaptic potentiation : TAS:ARUK-UCL
  • mating behavior : IGI:MGI
  • memory : TAS:ARUK-UCL
  • microglia development : ISO:MGI
  • modulation of age-related behavioral decline : ISO:MGI
  • modulation of excitatory postsynaptic potential : ISO:MGI
  • mRNA polyadenylation : IDA:MGI
  • negative regulation of cell proliferation : ISO:MGI
  • negative regulation of gene expression : ISO:MGI
  • negative regulation of long-term synaptic potentiation : ISO:MGI
  • negative regulation of neuron differentiation : IDA:MGI
  • neuromuscular process controlling balance : IGI:MGI
  • neuron apoptotic process : IGI:MGI
  • neuron projection development : IDA:MGI
  • neuron projection maintenance : ISO:MGI
  • neuron remodeling : IMP:MGI
  • Notch signaling pathway : IEA:UniProtKB-KW
  • positive regulation of amyloid fibril formation : ISO:MGI
  • positive regulation of amyloid-beta formation : ISO:MGI
  • positive regulation of astrocyte activation : ISO:MGI
  • positive regulation of DNA binding transcription factor activity : ISO:MGI
  • positive regulation of ERK1 and ERK2 cascade : ISO:MGI
  • positive regulation of G2/M transition of mitotic cell cycle : IMP:MGI
  • positive regulation of gene expression : ISO:MGI
  • positive regulation of JNK cascade : ISO:MGI
  • positive regulation of long-term synaptic potentiation : ISO:MGI
  • positive regulation of microglial cell activation : ISO:MGI
  • positive regulation of mitotic cell cycle : IMP:MGI
  • positive regulation of NF-kappaB transcription factor activity : ISO:MGI
  • positive regulation of NIK/NF-kappaB signaling : ISO:MGI
  • positive regulation of peptidyl-serine phosphorylation : ISO:MGI
  • positive regulation of peptidyl-threonine phosphorylation : ISO:MGI
  • positive regulation of phosphorylation : ISO:MGI
  • positive regulation of protein binding : ISO:MGI
  • positive regulation of protein metabolic process : ISO:MGI
  • positive regulation of protein phosphorylation : ISO:MGI
  • positive regulation of T cell migration : ISO:MGI
  • positive regulation of transcription by RNA polymerase II : IDA:MGI
  • protein homooligomerization : ISO:MGI
  • protein phosphorylation : IMP:MGI
  • regulation of epidermal growth factor-activated receptor activity : IGI:MGI
  • regulation of gene expression : IDA:MGI
  • regulation of long-term neuronal synaptic plasticity : ISO:MGI
  • regulation of multicellular organism growth : IMP:MGI
  • regulation of peptidyl-tyrosine phosphorylation : ISO:MGI
  • regulation of protein binding : IMP:MGI
  • regulation of spontaneous synaptic transmission : ISO:MGI
  • regulation of synapse structure or activity : IMP:MGI
  • regulation of translation : IDA:MGI
  • response to lead ion : IEA:Ensembl
  • response to oxidative stress : IGI:MGI
  • smooth endoplasmic reticulum calcium ion homeostasis : IGI:MGI
  • suckling behavior : IGI:MGI
  • synapse organization : ISO:MGI
  • synaptic growth at neuromuscular junction : IGI:MGI
  • tumor necrosis factor production : ISO:MGI
  • visual learning : IMP:MGI
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.