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NameAmyloid beta A4 protein
Synonyms
  • A4
  • ABPP
  • AD1
  • Alzheimer disease amyloid protein
  • APP
  • APPI
  • Cerebral vascular amyloid peptide
  • CVAP
  • PN-II
  • PreA4
  • Protease nexin-II
Gene NameAPP
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006619|Amyloid beta A4 protein
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Number of residues770
Molecular Weight86942.715
Theoretical pI4.45
GO Classification
Functions
  • DNA binding
  • receptor binding
  • PTB domain binding
  • identical protein binding
  • serine-type endopeptidase inhibitor activity
  • heparin binding
  • enzyme binding
  • peptidase activator activity
  • transition metal ion binding
  • acetylcholine receptor binding
Processes
  • blood coagulation
  • regulation of multicellular organism growth
  • post-Golgi vesicle-mediated transport
  • response to yeast
  • neuron remodeling
  • innate immune response
  • ionotropic glutamate receptor signaling pathway
  • neuron projection development
  • dendrite development
  • mating behavior
  • neuron apoptotic process
  • regulation of translation
  • negative regulation of endopeptidase activity
  • axon midline choice point recognition
  • extracellular matrix organization
  • positive regulation of mitotic cell cycle
  • collateral sprouting in absence of injury
  • cellular protein metabolic process
  • antibacterial humoral response
  • defense response to Gram-negative bacterium
  • regulation of epidermal growth factor-activated receptor activity
  • defense response to Gram-positive bacterium
  • Notch signaling pathway
  • regulation of synapse structure or activity
  • protein phosphorylation
  • antifungal humoral response
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • membrane organization
  • platelet degranulation
  • platelet activation
  • axon cargo transport
  • cellular copper ion homeostasis
  • visual learning
  • locomotory behavior
  • mRNA polyadenylation
  • endocytosis
  • cell adhesion
  • axonogenesis
  • adult locomotory behavior
Components
  • perinuclear region of cytoplasm
  • extracellular region
  • nuclear envelope lumen
  • integral component of plasma membrane
  • plasma membrane
  • receptor complex
  • intracellular membrane-bounded organelle
  • dendritic shaft
  • extracellular space
  • cell surface
  • platelet alpha granule lumen
  • coated pit
  • endosome lumen
  • trans-Golgi network membrane
  • dendritic spine
  • synapse
  • terminal bouton
  • membrane raft
  • Golgi apparatus
  • integral component of membrane
  • axon
  • cytoplasm
  • endosome
  • cytosol
  • extracellular exosome
General FunctionTransition metal ion binding
Specific FunctionFunctions 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.Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Pfam Domain Function
Transmembrane Regions700-723
GenBank Protein IDNot Available
UniProtKB IDP05067
UniProtKB Entry NameA4_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0019416|Amyloid beta A4 protein (APP)
ATGCTGCCCGGTTTGGCACTGCTCCTGCTGGCCGCCTGGACGGCTCGGGCGCTGGAGGTA
CCCACTGATGGTAATGCTGGCCTGCTGGCTGAACCCCAGATTGCCATGTTCTGTGGCAGA
CTGAACATGCACATGAATGTCCAGAATGGGAAGTGGGATTCAGATCCATCAGGGACCAAA
ACCTGCATTGATACCAAGGAAGGCATCCTGCAGTATTGCCAAGAAGTCTACCCTGAACTG
CAGATCACCAATGTGGTAGAAGCCAACCAACCAGTGACCATCCAGAACTGGTGCAAGCGG
GGCCGCAAGCAGTGCAAGACCCATCCCCACTTTGTGATTCCCTACCGCTGCTTAGTTGGT
GAGTTTGTAAGTGATGCCCTTCTCGTTCCTGACAAGTGCAAATTCTTACACCAGGAGAGG
ATGGATGTTTGCGAAACTCATCTTCACTGGCACACCGTCGCCAAAGAGACATGCAGTGAG
AAGAGTACCAACTTGCATGACTACGGCATGTTGCTGCCCTGCGGAATTGACAAGTTCCGA
GGGGTAGAGTTTGTGTGTTGCCCACTGGCTGAAGAAAGTGACAATGTGGATTCTGCTGAT
GCGGAGGAGGATGACTCGGATGTCTGGTGGGGCGGAGCAGACACAGACTATGCAGATGGG
AGTGAAGACAAAGTAGTAGAAGTAGCAGAGGAGGAAGAAGTGGCTGAGGTGGAAGAAGAA
GAAGCCGATGATGACGAGGACGATGAGGATGGTGATGAGGTAGAGGAAGAGGCTGAGGAA
CCCTACGAAGAAGCCACAGAGAGAACCACCAGCATTGCCACCACCACCACCACCACCACA
GAGTCTGTGGAAGAGGTGGTTCGAGAGGTGTGCTCTGAACAAGCCGAGACGGGGCCGTGC
CGAGCAATGATCTCCCGCTGGTACTTTGATGTGACTGAAGGGAAGTGTGCCCCATTCTTT
TACGGCGGATGTGGCGGCAACCGGAACAACTTTGACACAGAAGAGTACTGCATGGCCGTG
TGTGGCAGCGCCATGTCCCAAAGTTTACTCAAGACTACCCAGGAACCTCTTGCCCGAGAT
CCTGTTAAACTTCCTACAACAGCAGCCAGTACCCCTGATGCCGTTGACAAGTATCTCGAG
ACACCTGGGGATGAGAATGAACATGCCCATTTCCAGAAAGCCAAAGAGAGGCTTGAGGCC
AAGCACCGAGAGAGAATGTCCCAGGTCATGAGAGAATGGGAAGAGGCAGAACGTCAAGCA
AAGAACTTGCCTAAAGCTGATAAGAAGGCAGTTATCCAGCATTTCCAGGAGAAAGTGGAA
TCTTTGGAACAGGAAGCAGCCAACGAGAGACAGCAGCTGGTGGAGACACACATGGCCAGA
GTGGAAGCCATGCTCAATGACCGCCGCCGCCTGGCCCTGGAGAACTACATCACCGCTCTG
CAGGCTGTTCCTCCTCGGCCTCGTCACGTGTTCAATATGCTAAAGAAGTATGTCCGCGCA
GAACAGAAGGACAGACAGCACACCCTAAAGCATTTCGAGCATGTGCGCATGGTGGATCCC
AAGAAAGCCGCTCAGATCCGGTCCCAGGTTATGACACACCTCCGTGTGATTTATGAGCGC
ATGAATCAGTCTCTCTCCCTGCTCTACAACGTGCCTGCAGTGGCCGAGGAGATTCAGGAT
GAAGTTGATGAGCTGCTTCAGAAAGAGCAAAACTATTCAGATGACGTCTTGGCCAACATG
ATTAGTGAACCAAGGATCAGTTACGGAAACGATGCTCTCATGCCATCTTTGACCGAAACG
AAAACCACCGTGGAGCTCCTTCCCGTGAATGGAGAGTTCAGCCTGGACGATCTCCAGCCG
TGGCATTCTTTTGGGGCTGACTCTGTGCCAGCCAACACAGAAAACGAAGTTGAGCCTGTT
GATGCCCGCCCTGCTGCCGACCGAGGACTGACCACTCGACCAGGTTCTGGGTTGACAAAT
ATCAAGACGGAGGAGATCTCTGAAGTGAAGATGGATGCAGAATTCCGACATGACTCAGGA
TATGAAGTTCATCATCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACAAAGGT
GCAATCATTGGACTCATGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTG
GTGATGCTGAAGAAGAAACAGTACACATCCATTCATCATGGTGTGGTGGAGGTTGACGCC
GCTGTCACCCCAGAGGAGCGCCACCTGTCCAAGATGCAGCAGAACGGCTACGAAAATCCA
ACCTACAAGTTCTTTGAGCAGATGCAGAACTAG
GenBank Gene IDX06989
GeneCard IDNot Available
GenAtlas IDAPP
HGNC IDHGNC:620
Chromosome Location21
LocusNot Available
References
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