Amyloid beta A4 protein

Details

Name
Amyloid 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 Name
APP
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006619|Amyloid beta A4 protein
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
Number of residues
770
Molecular Weight
86942.715
Theoretical pI
4.45
GO Classification
Functions
acetylcholine receptor binding / DNA binding / enzyme binding / heparin binding / identical protein binding / peptidase activator activity / PTB domain binding / receptor binding / serine-type endopeptidase inhibitor activity / transition metal ion binding
Processes
adult locomotory behavior / antibacterial humoral response / antifungal humoral response / axon cargo transport / axon midline choice point recognition / axonogenesis / blood coagulation / cell adhesion / cellular copper ion homeostasis / cellular protein metabolic process / collateral sprouting in absence of injury / defense response to Gram-negative bacterium / defense response to Gram-positive bacterium / dendrite development / endocytosis / extracellular matrix organization / innate immune response / ionotropic glutamate receptor signaling pathway / locomotory behavior / mating behavior / membrane organization / mRNA polyadenylation / negative regulation of endopeptidase activity / neuron apoptotic process / neuron projection development / neuron remodeling / Notch signaling pathway / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / platelet activation / platelet degranulation / positive regulation of mitotic cell cycle / post-Golgi vesicle-mediated transport / protein phosphorylation / regulation of epidermal growth factor-activated receptor activity / regulation of multicellular organism growth / regulation of synapse structure or activity / regulation of translation / response to yeast / visual learning
Components
axon / cell surface / coated pit / cytoplasm / cytosol / dendritic shaft / dendritic spine / endosome / endosome lumen / extracellular exosome / extracellular region / extracellular space / Golgi apparatus / integral component of membrane / integral component of plasma membrane / intracellular membrane-bounded organelle / membrane raft / nuclear envelope lumen / perinuclear region of cytoplasm / plasma membrane / platelet alpha granule lumen / receptor complex / synapse / terminal bouton / trans-Golgi network membrane
General Function
Transition metal ion binding
Specific 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 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 Regions
700-723
Cellular Location
Membrane
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
Chromosome Location
21
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP05067
UniProtKB Entry NameA4_HUMAN
GenBank Gene IDX06989
GenAtlas IDAPP
HGNC IDHGNC:620
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02235L-methionine (R)-S-oxideexperimentalunknownDetails
DB05150CAD106investigationalunknownDetails
DB05846Mito-4509investigationalunknownDetails
DB05938EdonerpicinvestigationalunknownDetails
DB09148Florbetaben F-18approvedyesbinderDetails
DB09151Flutemetamol (18F)approved, investigationalyesbinderDetails
DB09149Florbetapir (18F)approved, investigationalyesbinderDetails
DB09130Copperapproved, investigationalunknownbinderDetails
DB00746Deferoxamineapproved, investigationalunknownDetails
DB06782DimercaprolapprovedunknownDetails
DB04892PhenserineinvestigationalunknownDetails
DB05088TetrathiomolybdateinvestigationalunknownDetails
DB01370Aluminiumapproved, investigationalunknownDetails
DB02709ResveratrolinvestigationalunknownDetails
DB01593Zincapproved, investigationalunknowncofactorDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14517Aluminium phosphateapproved, investigationalunknownDetails
DB14518Aluminum acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownligandDetails
DB14548Zinc sulfate, unspecified formapproved, experimentalunknownligandDetails
DB03754TromethamineapprovedunknowninhibitorDetails
DB12274Aducanumabapproved, investigationalunknownantagonistbinderantibodyDetails
DB12034GantenerumabinvestigationalyesantagonistbinderantibodyDetails
DB14580Lecanemabapproved, investigationalyesbinderDetails