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    APP amyloid beta (A4) precursor protein [ Homo sapiens ]

    Gene ID: 351, updated on 20-May-2012
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    Summary

    Official Symbol
    APPprovided by HGNC
    Official Full Name
    amyloid beta (A4) precursor proteinprovided by HGNC
    Primary source
    HGNC:620
    See related
    Ensembl:ENSG00000142192; HPRD:00100; MIM:104760; Vega:OTTHUMG00000078438
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AAA; AD1; PN2; ABPP; APPI; CVAP; ABETA; PN-II; CTFgamma
    Summary
    This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    21q21.3
    Sequence :
    Chromosome: 21; NC_000021.8 (27252861..27543446, complement)
    See APP in Epigenomics, MapViewer

    Chromosome 21 - NC_000021.8Genomic Context describing neighboring genes Neighboring gene junctional adhesion molecule 2 Neighboring gene ferredoxin 1 pseudogene 2 Neighboring gene ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F6 Neighboring gene GA binding protein transcription factor, alpha subunit 60kDa Neighboring gene uncharacterized LOC100289065 Neighboring gene myristoylated alanine-rich protein kinase C substrate pseudogene 1 Neighboring gene cysteine/tyrosine-rich 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Antiparallel β-sheet architecture in Iowa-mutant β-amyloid fibrils. Qiang W, et al. Proc Natl Acad Sci U S A, 2012 Mar 20. PMID 22403062.
    2. FBL2 regulates amyloid precursor protein (APP) metabolism by promoting ubiquitination-dependent APP degradation and inhibition of APP endocytosis. Watanabe T, et al. J Neurosci, 2012 Mar 7. PMID 22399757.
    3. Astrocyte-originated ATP protects Aβ(1-42)-induced impairment of synaptic plasticity. Jung ES, et al. J Neurosci, 2012 Feb 29. PMID 22378880.
    4. Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing. Matos MF, et al. Proc Natl Acad Sci U S A, 2012 Mar 6. PMID 22355143.
    5. Positional effects of phosphorylation on the stability and morphology of tau-related amyloid fibrils. Inoue M, et al. Biochemistry, 2012 Feb 21. PMID 22304362.

    See all (1392) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Neuronal-glial, astroglial and microglial cell types from Alzheimer brain each respond differently to Abeta42-peptide+tumor necrosis factoralpha-triggered stress.
      Title: Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells.
    2. Abeta42 was a stronger predictor of progression to Alzheimer's disease in APOE epsilon4 non-carriers than in carriers.
      Title: Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype.
    3. Infusion of an at-risk subpathogenic dose of amyloidbeta in chronically stressed rats causes significant impairment of cognitive functions and late-phase long-term potentiation, which may play a critical role in the etiology of Alzheimer's disease.
      Title: Chronic psychosocial stress accelerates impairment of long-term memory and late-phase long-term potentiation in an at-risk model of Alzheimer's disease.
    4. Alterations in the levels of amyloid protein precursor intracellular domain contribute to network dysfunction in Alzheimer's disease and transgenic model mice.
      Title: Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain.
    5. The study provides first evidence that a fraction of APP can associate via intermolecular disulfide bonds, likely generated between cysteines located in the extracellular E1 domain.
      Title: APP dimer formation is initiated in the endoplasmic reticulum and differs between APP isoforms.
    6. This study showed down regulation of PS1 and amyloidbeta42 in IMR32 cells transfected with siRNA against presenilin1. The results provide the rationale for therapeutic strategies aimed at influencing amyloidbeta42 production.
      Title: siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells.
    7. APP-presenilin 1 mutations enhance Abeta and disrupt basal excitability via divalent calcium (Ca2+)-dependent enhancement of afterhyperdepolarization, suggesting disruption of a learning-related Alzheimer's disease model of intrinsic excitability.
      Title: Mechanisms underlying basal and learning-related intrinsic excitability in a mouse model of Alzheimer's disease.
    8. Knockdown of retromer activity produces no change in the quantity or cellular distribution of total cellular APP and has no affect on internalization of cell-surface APP.
      Title: Retromer disruption promotes amyloidogenic APP processing.
    9. Data suggest that HEs-1/Hey-1 transcriptional modulation of insulin degrading enzyme may impact amyloid beta metabolism by providing a functional link between Notch signaling and the amyloidogenic pathway.
      Title: Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: implications for cellular Aβ metabolism.
    10. the antiparallel D23N-Abeta(1-40) fibril model represents a specific "toxic intermediate" in the aggregation process of a disease-associated Abeta mutant
      Title: Antiparallel β-sheet architecture in Iowa-mutant β-amyloid fibrils.
    Submit: New GeneRIF Correction See all (1114)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Alzheimer disease 1, familial

    Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants

    Dementia, early-onset progressive, autosomal recessive

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Transgenic (tg) mice overexpressing both human amyloid precursor proteins and HIV-1 gp120 at moderate levels show significantly less neuronal loss, synapto-dendritic degeneration, and gliosis than singly tg mice expressing gp120 alone PubMed
    Envelope transmembrane glycoprotein gp41 env A putative immunosuppressive domain (amino acids 583-599) of HIV-1 gp41 downregulates the interleukin 1beta- (IL-1beta) induced elevation of the secreted form of APP (sAPP alpha) PubMed
    Tat tat HIV-1 Tat treatment results in a 125% increase in soluble amyloid beta (Abeta) in brain cultures PubMed
    tat Binding of HIV-1 Tat to LRP inhibits neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha2-macroglobulin, apolipoprotein E4, amyloid precursor and amyloid beta-protein PubMed
    retropepsin gag-pol HIV-1 protease cleaves amyloid protein precursor at amino acid sites 200-201, 229-230, and 535-536 PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_000475.1 NP_003896.1 NAE1    BIND  PubMed The carboxy terminus of Amyloid Precursor Protein (APP) mediates an interaction with APP-BP1. 
    NP_000475.1 NP_000651.1 TGFB1    BIND  PubMed TGF-beta-1 interacts with Amyloid-beta. This interaction was modelled on a demonstrated interaction between TGF-beta-1 from an unspecified species and consensus Amyloid-beta peptides. 
    NP_000475.1 NP_003229.1 TGFB2    BIND  PubMed TGF-beta-2 interacts with Amyloid-beta. This interaction was modelled on a demonstrated interaction between TGF-beta-2 from an unspecified species and consensus Amyloid-beta peptides. 
    NP_000475.1     BIND  PubMed Amyloid-beta interacts with CR. This interaction was modeled on a demonstrated interaction between Amyloid-beta from an unspecified species and CR from a chemical source. 
    NP_000475.1     BIND  PubMed Amyloid-beta interacts with the FKBP12-SLF-CR complex. This interaction was modeled on a demonstrated interaction between Amyloid-beta from an unspecified species and the FKBP12-SLF-CR complex. 
    NP_958816.1 AAA61307.1 APBA1    BIND  PubMed APPswe interacts with X11-alpha. 
    NP_958816.1 NP_958816.1 APP    BIND  PubMed APP (Abeta) isoform b forms homodimers, homotrimers and oligomers. 
    NP_958816.1 NP_037379.1 HTRA2    BIND  PubMed HtrA2 interacts with APP. 
    NP_958816.1 NP_000012.1 PSEN1    BIND  PubMed PS1 interacts with APP. 
    NP_958816.1 NP_000012.1 PSEN1    BIND  PubMed PS1 interacts with APP751. 
    NP_958816.1 PSEN1    BIND  PubMed APPswe interacts with PS-1delta-9. 
    NP_958816.1 PSEN2    BIND  PubMed PS2 interacts with APP. 
    NP_958816.1     BIND  PubMed Amyloid-beta interacts with CR. This interaction was modeled on a demonstrated interaction between Amyloid-beta from an unspecified species and CR from a chemical source. 
    NP_958816.1     BIND  PubMed Amyloid-beta interacts with the FKBP12-SLF-CR complex. This interaction was modeled on a demonstrated interaction between Amyloid-beta from an unspecified species and the FKBP12-SLF-CR complex. 
    NP_958817.1 AAA61307.1 APBA1    BIND  PubMed Beta-APP interacts with X11. 
    NP_958817.1 NP_005447.1 MAPK8IP1    BIND  PubMed JIP1 interacts with APP. 
    NP_958817.1 NP_000012.1 PSEN1    BIND  PubMed PS1 interacts with APP via the APP-C100 fragment. 
    NP_958817.1 NP_000012.1 PSEN1    BIND  PubMed PS1 interacts with APP695. 
    NP_958817.1     BIND  PubMed Amyloid-beta interacts with CR. This interaction was modeled on a demonstrated interaction between Amyloid-beta from an unspecified species and CR from a chemical source. 
    NP_958817.1     BIND  PubMed Amyloid-beta interacts with the FKBP12-SLF-CR complex. This interaction was modeled on a demonstrated interaction between Amyloid-beta from an unspecified species and the FKBP12-SLF-CR complex. 
    P05067 P00519 ABL1    HPRD  PubMed  
    P05067 P22303 ACHE    HPRD  PubMed  
    P05067 Q02410 APBA1    HPRD  PubMed  
    P05067 Q99767 APBA2    HPRD  PubMed  
    P05067 O96018 APBA3    HPRD  PubMed  
    P05067 O00213 APBB1    HPRD  PubMed  
    P05067 Q92870 APBB2    HPRD  PubMed  
    P05067 O95704 APBB3    HPRD  PubMed  
    P05067 P02649 APOE    HPRD  PubMed  
    P05067 Q92624 APPBP2    HPRD  PubMed  
    P05067 P56817 BACE1    HPRD  PubMed  
    P05067 Q9Y5Z0 BACE2    HPRD  PubMed  
    P05067 P51572 BCAP31    HPRD  PubMed  
    P05067 P21810 BGN    HPRD  PubMed  
    P05067 Q13867 BLMH    HPRD  PubMed  
    P05067 P27797 CALR    HPRD  PubMed  
    P05067 P42574 CASP3    HPRD  PubMed  
    P05067 P49662 CASP4    HPRD  PubMed  
    P05067 P55212 CASP6    HPRD  PubMed  
    P05067 Q14790 CASP8    HPRD  PubMed  
    P05067 Q03135 CAV1    HPRD  PubMed  
    P05067 Q00535 CDK5    HPRD  PubMed  
    P05067 P36544 CHRNA7    HPRD  PubMed  
    P05067 P10909 CLU    HPRD  PubMed  
    P05067 P08123 COL1A2    HPRD  PubMed  
    P05067 Q9BXS0 COL25A1    HPRD  PubMed  
    P05067 P02462 COL4A1    HPRD  PubMed  
    P05067 P08572 COL4A2    HPRD  PubMed  
    P05067 Q01955 COL4A3    HPRD  PubMed  
    P05067 P29400 COL4A5    HPRD  PubMed  
    P05067 Q14031 COL4A6    HPRD  PubMed  
    P05067 P02511 CRYAB    HPRD  PubMed  
    P05067 P07339 CTSD    HPRD  PubMed  
    P05067 O75553 DAB1    HPRD  PubMed  
    P05067 P11171 EPB41    HPRD  PubMed  
    P05067 P00748 F12    HPRD  PubMed  
    P05067 P23142 FBLN1    HPRD  PubMed  
    P05067 O75955 FLOT1    HPRD  PubMed  
    P05067 P04406 GAPDH    HPRD  PubMed  
    P05067 P35052 GPC1    HPRD  PubMed  
    P05067 P62993 GRB2    HPRD  PubMed  
    P05067 P49841 GSK3B    HPRD  PubMed  
    P05067 P06396 GSN    HPRD  PubMed  
    P05067 P55084 HADHB    HPRD  PubMed  
    P05067 P30519 HMOX2    HPRD  PubMed  
    P05067 Q99714 HSD17B10    HPRD  PubMed  
    P05067 P98160 HSPG2    HPRD  PubMed  
    P05067 O43464 HTRA2    HPRD  PubMed  
    P05067 P14735 IDE    HPRD  PubMed  
    P05067 Q9Y287 ITM2B    HPRD  PubMed  
    P05067 Q92993 KAT5    HPRD  PubMed  
    P05067 Q07866 KLC1    HPRD  PubMed  
    P05067 P01042 KNG1    HPRD  PubMed  
    P05067 P25391 LAMA1    HPRD  PubMed  
    P05067 Q5SW96 LDLRAP1    HPRD  PubMed  
    P05067 Q07954 LRP1    HPRD  PubMed  
    P05067 Q9NZR2 LRP1B    HPRD  PubMed  
    P05067 Q9UQF2 MAPK8IP1    HPRD  PubMed  
    P05067 Q13387 MAPK8IP2    HPRD  PubMed  
    P05067 Q13564 NAE1    HPRD  PubMed  
    P05067 Q92542 NCSTN    HPRD  PubMed  
    P05067 Q96P71 NECAB3    HPRD  PubMed  
    P05067 P21359 NF1    HPRD  PubMed  
    P05067 P14543 NID1    HPRD  PubMed  
    P05067 P49757 NUMB    HPRD  PubMed  
    P05067 Q9Y6R0 NUMBL    HPRD  PubMed  
    P05067 Q13526 PIN1    HPRD  PubMed  
    P05067 Q08752 PPID    HPRD  PubMed  
    P05067 P07478 PRSS2    HPRD  PubMed  
    P05067 P35030 PRSS3    HPRD  PubMed  
    P05067 P49768 PSEN1    HPRD  PubMed  
    P05067 P49810 PSEN2    HPRD  PubMed  
    P05067 P01011 SERPINA3    HPRD  PubMed  
    P05067 P29353 SHC1    HPRD  PubMed  
    P05067 Q92529 SHC3    HPRD  PubMed  
    P05067 P37840 SNCA    HPRD  PubMed  
    P05067 Q16143 SNCB    HPRD  PubMed  
    P05067 Q9HCB6 SPON1    HPRD  PubMed  
    P05067 P01137 TGFB1    HPRD  PubMed  
    P05067 P61812 TGFB2    HPRD  PubMed  
    P05067 Beta amyloid binding protein TM2D1    HPRD  PubMed  
    P05067 Q13625 TP53BP2    HPRD  PubMed  
    P05067 Q8IVG9     HPRD  PubMed  
    BioGRID:106848 BioGRID:106561 ACHE    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:106817 APBA1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106848 BioGRID:106818 APBA2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:114920 APBA3    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:106819 APBB1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:106820 APBB2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:115593 APBB3    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:115769 APPBP2    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:248339 Apbb1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:198141 Apbb1    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:107102 BGN    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:107111 BLMH    BioGRID  PubMed Co-fractionation; Reconstituted Complex 
    BioGRID:106848 BioGRID:107262 CALR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:107305 CAV1    BioGRID  PubMed Co-fractionation; Protein-RNA 
    BioGRID:106848 BioGRID:116550 CLSTN1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:124143 COL25A1    BioGRID  PubMed Co-localization; Reconstituted Complex 
    BioGRID:106848 BioGRID:107970 DAB1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:107971 DAB2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:108486 FBLN1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:109189 GSN    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106848 BioGRID:200046 Grb2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:114593 HGS    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:109278 HSD17B10    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:106848 BioGRID:109552 HSP90AA1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:109540 HSPA4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:109561 HSPD1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:110029 KLC1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:114402 NAE1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106848 BioGRID:116961 NCSTN    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:111105 PARK2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:112316 SET    BioGRID  PubMed Protein-peptide 
    BioGRID:106848 BioGRID:112361 SHC1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:106848 BioGRID:112506 SNCA    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:112504 SNCB    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106848 BioGRID:115563 STUB1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:124085 SYVN1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:106848 BioGRID:203215 Shc1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:106848 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
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    General gene information

    Markers

    Genotypes

    Pathways from BioSystems

    • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
      Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
    • Advanced glycosylation endproduct receptor signaling, organism-specific biosystem (from REACTOME)
      Advanced glycosylation endproduct receptor signaling, organism-specific biosystemAdvanced Glycosylation End- product-specific Receptor (AGER) also known as Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand membrane receptor belonging to the immunoglobulin supe...
    • Alzheimer's disease, organism-specific biosystem (from KEGG)
      Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimer's disease, conserved biosystem (from KEGG)
      Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Amyloids, organism-specific biosystem (from REACTOME)
      Amyloids, organism-specific biosystemAmyloid is a term used to describe typically extracellular deposits of aggregated proteins, sometimes known as plaques. Abnormal accumulation of amyloid is amyloidosis, a term associated with disease...
    • Caspase cascade in apoptosis, organism-specific biosystem (from Pathway Interaction Database)
      Caspase cascade in apoptosis, organism-specific biosystem
      Caspase cascade in apoptosis
    • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
      Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
    • Cytosolic sensors of pathogen-associated DNA, organism-specific biosystem (from REACTOME)
      Cytosolic sensors of pathogen-associated DNA, organism-specific biosystemPresence of pathogen-associated DNA in cytosol induces type I IFN production. Several intracellular receptors have been implicated to some degree. These include DNA-dependent activator of interferon ...
    • DAI mediated induction of type I IFNs, organism-specific biosystem (from REACTOME)
      DAI mediated induction of type I IFNs, organism-specific biosystemDNA-dependent activator of IFN-regulatory factors (DAI), also known as Z-DNA-binding protein-1 (ZBP-1), was reported to initiate innate immune responses in murine L929 cells upon stimulation by multi...
    • Delta-Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Delta-Notch Signaling Pathway, organism-specific biosystemThere are 4 Notch receptors in humans (Notch 1-4) that bind to a family of 5 ligands (Jagged 1 and 2 and Delta-like 1-3). The Notch receptors are expressed on the cell surface as heterodimeric protei...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Formyl peptide receptors bind formyl peptides and many other ligands, organism-specific biosystem (from REACTOME)
      Formyl peptide receptors bind formyl peptides and many other ligands, organism-specific biosystemThe formyl peptide receptor (FPR) was defined pharmacologically in 1976 as a high affinity binding site on the surface of neutrophils for the peptide N-formyl-methionine-leucine-phenylalanine (fMLF)....
    • G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
    • G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • GPCR ligand binding, organism-specific biosystem (from REACTOME)
      GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
    • Glypican 1 network, organism-specific biosystem (from Pathway Interaction Database)
      Glypican 1 network, organism-specific biosystem
      Glypican 1 network
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Inflammasomes, organism-specific biosystem (from REACTOME)
      Inflammasomes, organism-specific biosystemIn contrast to NOD1/2 some NLRPs function as large macromolecular complexes called 'Inflammasomes'. These multiprotein platforms control activation of the cysteinyl aspartate protease caspase-1 and t...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • MyD88 cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88 cascade initiated on plasma membrane, organism-specific biosystemMammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of...
    • MyD88 dependent cascade initiated on endosome, organism-specific biosystem (from REACTOME)
      MyD88 dependent cascade initiated on endosome, organism-specific biosystemUpon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I ...
    • MyD88-independent cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88-independent cascade initiated on plasma membrane, organism-specific biosystemThe MyD88-independent signaling route utilizes TRAM and TRIF adapters, that are essential for production of both type 1 interferons(IFNs) and pro-inflammatory cytokines. TRAM is thought to bridge bet...
    • MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystemThe first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also b...
    • NFkB and MAP kinases activation mediated by TLR4 signaling repertoire, organism-specific biosystem (from REACTOME)
      NFkB and MAP kinases activation mediated by TLR4 signaling repertoire, organism-specific biosystemMitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascade tr...
    • Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystem (from REACTOME)
      Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystemThe innate immune system is the first line of defense against invading microorganisms, a broad specificity response characterized by the recruitment and activation of phagocytes and the release of an...
    • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
      Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • Platelet degranulation, organism-specific biosystem (from REACTOME)
      Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
    • RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystem (from REACTOME)
      RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystemRIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. F...
    • RIP-mediated NFkB activation via DAI, organism-specific biosystem (from REACTOME)
      RIP-mediated NFkB activation via DAI, organism-specific biosystemOverexpression of human or murine DAI in human embryonic kidney 293T cells (HEK293T) activated NF-kB-dependent promoter in a dose-dependent manner. Two RHIM-contaning kinases RIP1 and RIP3 are implic...
    • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
      Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
    • Serotonergic synapse, organism-specific biosystem (from KEGG)
      Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • TAK1 activates NFkB by phosphorylation and activation of IKKs complex, organism-specific biosystem (from REACTOME)
      TAK1 activates NFkB by phosphorylation and activation of IKKs complex, organism-specific biosystemNF-kappaB is sequestered in the cytoplasm in a complex with inhibitor of NF-kappaB (IkB). Almost all NF-kappaB activation pathways are mediated by IkB kinase (IKK), which phosphorylates IkB resulting...
    • TRAF6 Mediated Induction of proinflammatory cytokines, organism-specific biosystem (from REACTOME)
      TRAF6 Mediated Induction of proinflammatory cytokines, organism-specific biosystemIn human, together with ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A (also known as UBE2V1), TRAF6 catalyses Lys63-linked ubiquitination. It is believed that auto polyubiquitination and oli...
    • TRAF6 mediated NF-kB activation, organism-specific biosystem (from REACTOME)
      TRAF6 mediated NF-kB activation, organism-specific biosystemThe TRAF6/TAK1 signal activates a canonical IKK complex, resulting in the activation of NF-kB as well as MAPK cascades leading to the activation of AP-1. Although TRAF6/TAK1 has been implicated in To...
    • TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystem (from REACTOME)
      TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystemTRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.
    • TRIF mediated TLR3 signaling, organism-specific biosystem (from REACTOME)
      TRIF mediated TLR3 signaling, organism-specific biosystemTIR-domain-containing adaptor inducing interferon-beta (TRIF or TIKAM1) is known to be an essential and exclusive adaptor used by TLR3; all the poly(I:C)-induced pathways leading to NFkB and IRF3 act...
    • The NLRP3 inflammasome, organism-specific biosystem (from REACTOME)
      The NLRP3 inflammasome, organism-specific biosystemThe NLRP3 (Cryopyrin) inflammasome is currently the best characterized. It consists of NLRP3, ASC (PYCARD) and procaspase-1; CARD8 (Cardinal) is also suggested to be a component. It is activated by a...
    • Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystemLittle is known about TLR10 ligands. It has been established that the receptor homodimerizes upon binding and signals in an MyD88-dependent manner (Hasan U et al 2005; Nyman T et al 2008). It may als...
    • Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystemTLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at le...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
    • Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystemTLR5 is the receptor for flagellin, the protein that forms bacterial flagella. Unlike most other Pathogen-Associated Molecular Patterns (PAMPs), flagellin does not undergo any posttranslational modif...
    • Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystemRNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich...
    • Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystemCpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated....
    • Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystemTLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial...
    • Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystemTLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recog...
    • Toll Receptor Cascades, organism-specific biosystem (from REACTOME)
      Toll Receptor Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
    • Viral dsRNA:TLR3:TRIF Complex Activates RIP1, organism-specific biosystem (from REACTOME)
      Viral dsRNA:TLR3:TRIF Complex Activates RIP1, organism-specific biosystemReceptor-interacting protein 1 (RIP1) mediates the activation of interferon-alpha/beta via intermediate activation of IKK/TBK1 or NFkB pathways.
    • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
      p75(NTR)-mediated signaling, organism-specific biosystem
      p75(NTR)-mediated signaling

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    PTB domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    acetylcholine receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    heparin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    peptidase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    peptidase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    serine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    transition metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    G2 phase of mitotic cell cycle ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Notch signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    adult locomotory behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    axon cargo transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    axon midline choice point recognition ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    axonogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    blood coagulation TAS
    Traceable Author Statement
    more info
    		  
    cell adhesion IEA
    Inferred from Electronic Annotation
    more info
    		  
    cell death IEA
    Inferred from Electronic Annotation
    more info
    		  
    cellular copper ion homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    collateral sprouting in absence of injury ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    dendrite development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    endocytosis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    extracellular matrix organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    forebrain development IEA
    Inferred from Electronic Annotation
    more info
    		  
    induction of apoptosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    innate immune response TAS
    Traceable Author Statement
    more info
    		  
    ionotropic glutamate receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    locomotory behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    mRNA polyadenylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    mating behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    neuromuscular process controlling balance IEA
    Inferred from Electronic Annotation
    more info
    		  
    neuron apoptosis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    neuron projection development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    neuron remodeling ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    platelet activation TAS
    Traceable Author Statement
    more info
    		  
    platelet degranulation TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of mitotic cell cycle ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of transcription from RNA polymerase II promoter IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    regulation of epidermal growth factor-activated receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of multicellular organism growth ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    regulation of synapse structure and activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    regulation of translation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    smooth endoplasmic reticulum calcium ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    suckling behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    synaptic growth at neuromuscular junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    visual learning ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Golgi apparatus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    apical part of cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    axon ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    ciliary rootlet IEA
    Inferred from Electronic Annotation
    more info
    		  
    coated pit IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    cytoplasmic vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    dendritic shaft IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    dendritic spine IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
    		  
    integral to membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    integral to plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    neuromuscular junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    platelet alpha granule lumen TAS
    Traceable Author Statement
    more info
    		  
    spindle midzone IEA
    Inferred from Electronic Annotation
    more info
    		  
    synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    synaptosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    amyloid beta A4 protein
    Names
    amyloid beta A4 protein
    preA4
    protease nexin-II
    peptidase nexin-II
    beta-amyloid peptide
    alzheimer disease amyloid protein
    cerebral vascular amyloid peptide
    Help top of page

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007376.1 RefSeqGene

      Range
      4687..295272
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000484.3 → NP_000475.1  amyloid beta A4 protein isoform a precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a, also known as PreA4 770).
      Source sequence(s)
      AK312326, BC065529, BI559391, BM876312
      Consensus CDS
      CCDS13576.1
      UniProtKB/Swiss-Prot
      P05067
      Related
      ENSP00000284981, OTTHUMP00000096098, ENST00000346798, OTTHUMT00000171340
      Conserved Domains (8) summary
      cd00109
      Location:291 – 342
      Blast Score: 219
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam03494
      Location:672 – 705
      Blast Score: 123
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:24 – 188
      Blast Score: 829
      A4_EXTRA; amyloid A4
      pfam10515
      Location:724 – 766
      Blast Score: 220
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:30 – 131
      Blast Score: 473
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:132 – 188
      Blast Score: 301
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam11740
      Location:407 – 474
      Blast Score: 83
      KfrA_N; Plasmid replication region DNA-binding N-term
      pfam12925
      Location:365 – 549
      Blast Score: 720
      APP_E2; E2 domain of amyloid precursor protein

    2. NM_001136016.3 → NP_001129488.1  amyloid beta A4 protein isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (d) has a shorter and distinct N-terminus and lacks an internal segment compared to isoform a.
      Source sequence(s)
      AK295621, AK311717, BM876312, Y00264
      Consensus CDS
      CCDS56212.1
      Related
      ENSP00000387483, ENST00000440126
      Conserved Domains (8) summary
      cd00109
      Location:286 – 337
      Blast Score: 218
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam03494
      Location:648 – 681
      Blast Score: 123
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:19 – 183
      Blast Score: 831
      A4_EXTRA; amyloid A4
      pfam10515
      Location:700 – 742
      Blast Score: 220
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:25 – 126
      Blast Score: 472
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:127 – 183
      Blast Score: 301
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam11740
      Location:383 – 450
      Blast Score: 84
      KfrA_N; Plasmid replication region DNA-binding N-term
      pfam12925
      Location:341 – 525
      Blast Score: 726
      APP_E2; E2 domain of amyloid precursor protein

    3. NM_001136129.2 → NP_001129601.1  amyloid beta A4 protein isoform e precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks three alternate in-frame exons compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AF282245, BC065529, BI559391, BM876312
      Consensus CDS
      CCDS46638.1
      UniProtKB/Swiss-Prot
      P05067
      Related
      ENSP00000346129, OTTHUMP00000096096, ENST00000354192, OTTHUMT00000171338
      Conserved Domains (5) summary
      pfam03494
      Location:541 – 574
      Blast Score: 120
      Beta-APP; Beta-amyloid peptide (beta-APP)
      pfam10515
      Location:593 – 635
      Blast Score: 215
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:19 – 75
      Blast Score: 282
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:76 – 132
      Blast Score: 308
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam12925
      Location:238 – 418
      Blast Score: 681
      APP_E2; E2 domain of amyloid precursor protein

    4. NM_001136130.2 → NP_001129602.1  amyloid beta A4 protein isoform f precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (f) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AK294534, BC065523, BC065529, BI559391, BM876312
      Consensus CDS
      CCDS46639.1
      UniProtKB/TrEMBL
      B4DGD0
      UniProtKB/TrEMBL
      E9PG40
      UniProtKB/Swiss-Prot
      P05067
      Related
      ENSP00000398879, OTTHUMP00000225525, ENST00000439274, OTTHUMT00000376685
      Conserved Domains (6) summary
      cd00109
      Location:235 – 286
      Blast Score: 221
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam03494
      Location:616 – 649
      Blast Score: 122
      Beta-APP; Beta-amyloid peptide (beta-APP)
      pfam10515
      Location:668 – 710
      Blast Score: 218
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:19 – 75
      Blast Score: 280
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:76 – 132
      Blast Score: 302
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam12925
      Location:309 – 493
      Blast Score: 710
      APP_E2; E2 domain of amyloid precursor protein

    5. NM_001136131.2 → NP_001129603.1  amyloid beta A4 protein isoform g

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR and coding sequence and lacks two alternate in-frame exons compared to variant 1. The resulting isoform (g) is shorter at the N-terminus and lacks an internal segment compared to isoform a.
      Source sequence(s)
      AK296229, BM876312, Y00264
      Consensus CDS
      CCDS56211.1
      Related
      ENSP00000388538, ENST00000448388
      Conserved Domains (6) summary
      pfam03494
      Location:562 – 595
      Blast Score: 121
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:1 – 153
      Blast Score: 791
      A4_EXTRA; amyloid A4
      pfam10515
      Location:614 – 656
      Blast Score: 217
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:1 – 96
      Blast Score: 444
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:97 – 153
      Blast Score: 304
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam12925
      Location:259 – 439
      Blast Score: 692
      APP_E2; E2 domain of amyloid precursor protein

    6. NM_001204301.1 → NP_001191230.1  amyloid beta A4 protein isoform h precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (h, also known as L-APP752) has the same N- and C-termini but is shorter compared to isoform a. No full-length transcript is available for this transcript; however, it is supported by PMID:1429732 and other publications.
      Source sequence(s)
      AK294534, AK312326, BI559391, BM876312, Y00264
      Consensus CDS
      CCDS56213.1
      UniProtKB/TrEMBL
      B4DGD0
      UniProtKB/Swiss-Prot
      P05067
      Related
      ENSP00000351796, ENST00000358918
      Conserved Domains (8) summary
      cd00109
      Location:291 – 342
      Blast Score: 217
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam03494
      Location:654 – 687
      Blast Score: 122
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:24 – 188
      Blast Score: 828
      A4_EXTRA; amyloid A4
      pfam10515
      Location:706 – 748
      Blast Score: 220
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:30 – 131
      Blast Score: 472
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:132 – 188
      Blast Score: 299
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam11740
      Location:407 – 474
      Blast Score: 84
      KfrA_N; Plasmid replication region DNA-binding N-term
      pfam12925
      Location:365 – 549
      Blast Score: 720
      APP_E2; E2 domain of amyloid precursor protein

    7. NM_001204302.1 → NP_001191231.1  amyloid beta A4 protein isoform i precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) lacks two alternate in-frame exons compared to variant 1. The resulting isoform (i, also known as L-APP733) has the same N- and C-termini but is shorter compared to isoform a. No full-length transcript is available for this transcript; however, it is supported by PMID:1429732 and other publications.
      Source sequence(s)
      BI559391, BM876312, X06989, Y00264
      UniProtKB/Swiss-Prot
      P05067
      Conserved Domains (8) summary
      cd00109
      Location:291 – 342
      Blast Score: 216
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam03494
      Location:635 – 668
      Blast Score: 122
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:24 – 188
      Blast Score: 827
      A4_EXTRA; amyloid A4
      pfam10515
      Location:687 – 729
      Blast Score: 220
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:30 – 131
      Blast Score: 471
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:132 – 188
      Blast Score: 298
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam11740
      Location:388 – 455
      Blast Score: 84
      KfrA_N; Plasmid replication region DNA-binding N-term
      pfam12925
      Location:346 – 530
      Blast Score: 723
      APP_E2; E2 domain of amyloid precursor protein

    8. NM_001204303.1 → NP_001191232.1  amyloid beta A4 protein isoform j precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) lacks three alternate in-frame exons compared to variant 1. The resulting isoform (j, also known as L-APP677) has the same N- and C-termini but is shorter compared to isoform a. No full-length transcript is available for this transcript; however, it is supported by PMID:1429732 and other publications.
      Source sequence(s)
      BI559391, BM876312, Y00264
      UniProtKB/Swiss-Prot
      P05067
      Conserved Domains (6) summary
      pfam03494
      Location:579 – 612
      Blast Score: 120
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:24 – 188
      Blast Score: 836
      A4_EXTRA; amyloid A4
      pfam10515
      Location:631 – 673
      Blast Score: 217
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:30 – 131
      Blast Score: 475
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:132 – 188
      Blast Score: 304
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam12925
      Location:294 – 474
      Blast Score: 693
      APP_E2; E2 domain of amyloid precursor protein

    9. NM_201413.2 → NP_958816.1  amyloid beta A4 protein isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b, also known as PreA4 751) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      BC065529, BI559391, BM876312
      Consensus CDS
      CCDS33523.1
      UniProtKB/Swiss-Prot
      P05067
      Related
      ENSP00000350578, OTTHUMP00000096095, ENST00000357903, OTTHUMT00000171337
      Conserved Domains (8) summary
      cd00109
      Location:291 – 342
      Blast Score: 217
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam03494
      Location:653 – 686
      Blast Score: 122
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:24 – 188
      Blast Score: 828
      A4_EXTRA; amyloid A4
      pfam10515
      Location:705 – 747
      Blast Score: 220
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:30 – 131
      Blast Score: 472
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:132 – 188
      Blast Score: 300
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam11740
      Location:388 – 455
      Blast Score: 83
      KfrA_N; Plasmid replication region DNA-binding N-term
      pfam12925
      Location:346 – 530
      Blast Score: 723
      APP_E2; E2 domain of amyloid precursor protein

    10. NM_201414.2 → NP_958817.1  amyloid beta A4 protein isoform c precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (c, also known as PreA4 695) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      BI559391, BM876312, Y00264
      Consensus CDS
      CCDS13577.1
      UniProtKB/Swiss-Prot
      P05067
      Related
      ENSP00000345463, OTTHUMP00000096097, ENST00000348990, OTTHUMT00000171339
      Conserved Domains (6) summary
      pfam03494
      Location:597 – 630
      Blast Score: 121
      Beta-APP; Beta-amyloid peptide (beta-APP)
      smart00006
      Location:24 – 188
      Blast Score: 838
      A4_EXTRA; amyloid A4
      pfam10515
      Location:649 – 691
      Blast Score: 217
      APP_amyloid; beta-amyloid precursor protein C-terminus
      pfam02177
      Location:30 – 131
      Blast Score: 476
      APP_N; Amyloid A4 N-terminal heparin-binding
      pfam12924
      Location:132 – 188
      Blast Score: 306
      APP_Cu_bd; Copper-binding of amyloid precursor, CuBD
      pfam12925
      Location:294 – 474
      Blast Score: 694
      APP_E2; E2 domain of amyloid precursor protein

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000021.8 Reference GRCh37.p5 Primary Assembly

      Range
      27252861..27543446, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000153.1 Alternate HuRef

      Range
      12656350..12947965, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AP001439.1 None
    genomic AP001440.1 None
    genomic AP001441.1 None
    genomic AP001442.1 None
    genomic AP001443.1 (5968..35952) None
    genomic AY011354.1 AAG47389.1
    genomic AY919674.1 AAW82435.1
    genomic CH471079.2 EAX09957.1
      EAX09958.1
      EAX09959.1
      EAX09960.1
      EAX09961.1
      EAX09962.1
      EAX09963.1
      EAX09964.1
      EAX09965.1
      EAX09966.1
    genomic CS275872.1 CAJ84410.1
    genomic CS365133.1 CAL33835.1
    genomic CS448142.1 CAL69831.1
    genomic CS448144.1 CAL69791.1
    genomic CS448146.1 CAL69792.1
    genomic CS448164.1 CAL69838.1
    genomic CS448166.1 CAL69795.1
    genomic CS448168.1 CAL69796.1
    genomic D87675.1 BAA22264.1
    genomic M24546.1 AAC13654.1
    genomic M29270.1 AAA51768.1
    genomic M33112.1 AAB59502.1
    genomic M34862.1 AAB59502.1
    genomic M34863.1 AAB59502.1
    genomic M34864.1 AAB59502.1
    genomic M34865.1 AAB59502.1
    genomic M34866.1 AAB59502.1
    genomic M34867.1 AAB59502.1
    genomic M34868.1 AAB59502.1
    genomic M34869.1 AAB59502.1
    genomic M34870.1 AAB59502.1
    genomic M34871.1 AAB59502.1
    genomic M34872.1 AAB59502.1
    genomic M34873.1 AAB59502.1
    genomic M34874.1 AAB59502.1
    genomic M34875.1 AAB59501.1
    genomic M34876.1 AAB59502.1
    genomic M34877.1 AAB59502.1
    genomic M34878.1 AAB59502.1
    genomic M34879.1 AAB59502.1
    genomic M37896.1 AAA51727.1
    genomic S45136.1 AAB23646.1
    genomic S60317.1 AAC60601.2
    genomic X13466.1 CAA31830.1
    mRNA AB066441.2 BAB71958.2
    mRNA AF282245.1 AAQ14327.1
    mRNA AK294534.1 BAG57741.1
    mRNA AK295373.1 BAH12049.1
    mRNA AK295621.1 BAG58500.1
    mRNA AK296229.1 BAG58951.1
    mRNA AK297229.1 BAG59712.1
    mRNA AK297412.1 BAG59847.1
    mRNA AK298861.1 BAG60983.1
    mRNA AK311717.1 None
    mRNA AK312326.1 BAG35248.1
    mRNA BC004369.1 AAH04369.1
    mRNA BC065523.1 None
    mRNA BC065529.1 AAH65529.1
    mRNA BE907745.1 None
    mRNA BI559391.1 None
    mRNA BM172428.1 None
    mRNA BM876312.1 None
    mRNA CB854706.1 None
    mRNA DC336035.1 None
    mRNA M15532.1 AAA51564.1
    mRNA M15533.1 AAA35540.1
    mRNA M16765.1 AAA51722.1
    mRNA M18734.1 AAA51726.1
    mRNA M28373.1 AAA58727.1
    mRNA M35675.1 AAA60163.1
    mRNA S41243.1 None
    mRNA S60721.1 AAB26263.2
    mRNA S61380.1 AAB26264.2
    mRNA S61383.1 AAB26265.2
    mRNA X06981.1 CAA30041.1
    mRNA X06982.1 CAA30042.1
    mRNA X06989.1 CAA30050.1
    mRNA Y00264.1 CAA68374.1
    mRNA A02759.1 CAA00268.1
    other-genetic EU832797.1 ACE87808.1
    other-genetic GQ129348.1 ACT64482.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P05067.3 GenPept UniProtKB/Swiss-Prot:P05067
    Q9BYY9 GenPept UniProtKB/TrEMBL:Q9BYY9
    Help top of page

    Additional Links

    Additional Links

    Gene LinkOut

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