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UniProtKB/Swiss-Prot entry P12023


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name A4_MOUSE
Primary accession number P12023
Secondary accession numbers P97487 P97942 Q99K32
Integrated into Swiss-Prot on October 1, 1989
Sequence was last modified on May 9, 2003 (Sequence version 3)
Annotations were last modified on    June 16, 2009 (Entry version 129)
Name and origin of the protein
Protein name Amyloid beta A4 protein [Precursor]
Synonyms Alzheimer disease amyloid A4 protein homolog
ABPP
APP
Amyloidogenic glycoprotein
AG
Contains Soluble APP-alpha
     (S-APP-alpha)
Soluble APP-beta
     (S-APP-beta)
C99
     (APP-C99)
Beta-amyloid protein 42
     (Beta-APP42)
Beta-amyloid protein 40
     (Beta-APP40)
C83
P3(42)
P3(40)
Gamma-secretase C-terminal fragment 59
     (Gamma-CTF(59))
     (Amyloid intracellular domain 59)
     (AID(59))
     (APP-C59)
Gamma-secretase C-terminal fragment 57
     (Gamma-CTF(57))
     (Amyloid intracellular domain 57)
     (AID(57))
     (APP-C57)
Gamma-secretase C-terminal fragment 50
     (Gamma-CTF(50))
     (Amyloid intracellular domain 50)
     (AID(50))
C31
Gene name
Name: App
From
Mus musculus (Mouse) [TaxID: 10090] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
TISSUE=Brain;
DOI=10.1016/0006-291X(87)90419-0; PubMed=3322280 [NCBI, ExPASy, EBI, Israel, Japan]
Yamada T., Sasaki H., Furuya H., Miyata T., Goto I., Sakaki Y.;
"Complementary DNA for the mouse homolog of the human amyloid beta protein precursor.";
Biochem. Biophys. Res. Commun. 149:665-671(1987).
[2]
SEQUENCE REVISION.
Yamada T.;
Submitted (MAR-1988) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
STRAIN=BALB/c;
TISSUE=Brain;
DOI=10.1016/0167-4781(91)90231-A; PubMed=1756177 [NCBI, ExPASy, EBI, Israel, Japan]
de Strooper B., van Leuven F., van den Berghe H.;
"The amyloid beta protein precursor or proteinase nexin II from mouse is closer related to its human homolog than previously reported.";
Biochim. Biophys. Acta 1129:141-143(1991).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
STRAIN=SAMP8;
TISSUE=Hippocampus;
DOI=10.1139/bcb-79-1-57; PubMed=11235921 [NCBI, ExPASy, EBI, Israel, Japan]
Kumar V.B., Vyas K., Franko M., Choudhary V., Buddhiraju C., Alvarez J., Morley J.E.;
"Molecular cloning, expression, and regulation of hippocampal amyloid precursor protein of senescence accelerated mouse (SAMP8).";
Biochem. Cell Biol. 79:57-67(2001).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19.
DOI=10.1016/0378-1119(92)90375-Y; PubMed=1555768 [NCBI, ExPASy, EBI, Israel, Japan]
Izumi R., Yamada T., Yoshikai S., Sasaki H., Hattori M., Sakai Y.;
"Positive and negative regulatory elements for the expression of the Alzheimer's disease amyloid precursor-encoding gene in mouse.";
Gene 112:189-195(1992).
[6]
PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM APP770).
TISSUE=Mammary tumor;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 281-380, AND ALTERNATIVE SPLICING.
TISSUE=Brain, and Kidney;
DOI=10.1016/0006-291X(89)92808-8; PubMed=2493250 [NCBI, ExPASy, EBI, Israel, Japan]
Yamada T., Sasaki H., Dohura K., Goto I., Sakaki Y.;
"Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer's disease amyloid beta protein precursor.";
Biochem. Biophys. Res. Commun. 158:906-912(1989).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 289-364.
STRAIN=CD-1;
TISSUE=Placenta;
DOI=10.1093/nar/17.13.5396; PubMed=2569710 [NCBI, ExPASy, EBI, Israel, Japan]
Fukuchi K., Martin G.M., Deeb S.S.;
"Sequence of the protease inhibitor domain of the A4 amyloid protein precursor of Mus domesticus.";
Nucleic Acids Res. 17:5396-5396(1989).
[9]
NUCLEOTIDE SEQUENCE OF 656-737.
STRAIN=129/Sv;
Wragg M.A., Busfield F., Duff K., Korenblat K., Capecchi M., Loring J.F., Goate A.M.;
"Introduction of six mutations into the mouse genome using 'Hit and Run' gene-targeting: introduction of familial Alzheimer's disease mutations into the mouse amyloid precursor protein gene and humanization of the A-beta fragment.";
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
[10]
TISSUE SPECIFICITY OF ALTERNATIVE SPLICED FORMS.
DOI=10.1016/0169-328X(93)90020-P; PubMed=8510506 [NCBI, ExPASy, EBI, Israel, Japan]
Sola C., Mengod G., Ghetti B., Palacios J.M., Triarhou L.C.;
"Regional distribution of the alternatively spliced isoforms of beta APP RNA transcript in the brain of normal, heterozygous and homozygous weaver mutant mice as revealed by in situ hybridization histochemistry.";
Brain Res. Mol. Brain Res. 17:340-346(1993).
[11]
INTERACTION WITH KNS2.
DOI=10.1016/S0896-6273(00)00124-0; PubMed=11144355 [NCBI, ExPASy, EBI, Israel, Japan]
Kamal A., Stokin G.B., Yang Z., Xia C.-H., Goldstein L.S.;
"Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I.";
Neuron 28:449-459(2000).
[12]
C-TERMINAL PROTEIN-PROTEIN INTERACTION, AND MUTAGENESIS OF TYR-728; THR-743; TYR-757; ASN-759 AND TYR-762.
PubMed=11517249 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuda S., Yasukawa T., Homma Y., Ito Y., Niikura T., Hiraki T., Hirai S., Ohno S., Kita Y., Kawasumi M., Kouyama K., Yamamoto T., Kyriakis J.M., Nishimoto I.;
"C-jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK.";
J. Neurosci. 21:6597-6607(2001).
[13]
INTERACTION WITH MAPK8IP1, AND PHOSPHORYLATION.
DOI=10.1074/jbc.M108372200; PubMed=11912189 [NCBI, ExPASy, EBI, Israel, Japan]
Taru H., Iijima K., Hase M., Kirino Y., Yagi Y., Suzuki T.;
"Interaction of Alzheimer's beta-amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade.";
J. Biol. Chem. 277:20070-20078(2002).
[14]
INTERACTION OF CTF PEPTIDES WITH NUMB.
DOI=10.1073/pnas.102192599; PubMed=12011466 [NCBI, ExPASy, EBI, Israel, Japan]
Roncarati R., Sestan N., Scheinfeld M.H., Berechid B.E., Lopez P.A., Meucci O., McGlade J.C., Rakic P., D'Adamio L.;
"The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling.";
Proc. Natl. Acad. Sci. U.S.A. 99:7102-7107(2002).
[15]
PROTEOLYTIC PROCESSING BY GAMMA SECRETASE, AND INTERACTION WITH APBB1.
DOI=10.1046/j.1471-4159.2001.00516.x; PubMed=11553691 [NCBI, ExPASy, EBI, Israel, Japan]
Cupers P., Orlans I., Craessaerts K., Annaert W., De Strooper B.;
"The amyloid precursor protein (APP)-cytoplasmic fragment generated by gamma-secretase is rapidly degraded but distributes partially in a nuclear fraction of neurons in culture.";
J. Neurochem. 78:1168-1178(2001).
[16]
INTERACTION WITH CPEB1.
DOI=10.1128/MCB.25.24.10930-10939.2005; PubMed=16314516 [NCBI, ExPASy, EBI, Israel, Japan]
Cao Q., Huang Y.-S., Kan M.-C., Richter J.D.;
"Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation.";
Mol. Cell. Biol. 25:10930-10939(2005).
Comments
  • 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-HTATIP 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 (By similarity).
  • FUNCTION: Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation (By similarity).
  • FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
  • SUBUNIT: Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1, Numb and Dab1. Binding to Dab1 inhibits its serine phosphorylation. Also interacts with GPCR-like protein BPP, FPRL1, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1 (By similarity). In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1 (By similarity). Amyloid beta-42 binds CHRNA7 in hippocampal neurons (By similarity). Beta-amyloid associates with HADH2 (By similarity). Interacts with ANKS1B (By similarity). Interacts with CPEB1.
  • INTERACTION:
    P35331:- (xeno); NbExp=1; IntAct=EBI-286828, EBI-2028081;
    P98084:Apba2; NbExp=1; IntAct=EBI-78814, EBI-81669;
    Q9QXJ1:Apbb1; NbExp=1; IntAct=EBI-78814, EBI-81338;
    Q03157:Aplp1; NbExp=2; IntAct=EBI-78814, EBI-399929;
    Q06335:Aplp2; NbExp=1; IntAct=EBI-78814, EBI-446708;
    Q9P232:CNTN3 (xeno); NbExp=1; IntAct=EBI-286828, EBI-2028361;
    Q8IWV2:CNTN4 (xeno); NbExp=1; IntAct=EBI-286828, EBI-2028276;
    P97318:Dab1; NbExp=1; IntAct=EBI-78814, EBI-81680;
    Q9D1T0:Lingo1; NbExp=1; IntAct=EBI-78814, EBI-2012981;
    Q9UQF2:MAPK8IP1 (xeno); NbExp=1; IntAct=EBI-78814, EBI-78404;
    Q9UQF2:MAPK8IP1 (xeno); NbExp=1; IntAct=EBI-286828, EBI-78404;
    Q9WVI9:Mapk8ip1; NbExp=2; IntAct=EBI-78814, EBI-74515;
    Q9WVI9-1:Mapk8ip1; NbExp=2; IntAct=EBI-78814, EBI-288461;
    Q9WVI9-1:Mapk8ip1; NbExp=1; IntAct=EBI-286828, EBI-288461;
    Q61120:Shc3; NbExp=1; IntAct=EBI-78814, EBI-79107;
  • SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. Membrane, clathrin-coated pit. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. 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. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FPRL1 at the cell surface and the complex is then rapidly internalized (By similarity). APP sorts to the basolateral surface in epithelial cells (By similarity). 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).
  • ALTERNATIVE PRODUCTS: 4 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist.
    NameAPP770
    Isoform IDP12023-1
    This is the isoform sequence displayed in this entry.
    NameAPP695
    Isoform IDP12023-2
    Features which should be applied to build the isoform sequence: VSP_000012, VSP_000013.
    NameAPP751
    Isoform IDP12023-3
    Features which should be applied to build the isoform sequence: VSP_000014.
    NameAPP714
    Isoform IDP12023-4
    The sequence of this isoform is not described.
  • TISSUE SPECIFICITY: Isoform APP770 is expressed in kidney. Isoform APP751 is widely expressed. Isoform APP695 is expressed in brain, kidney and liver. Isoform APP695, isoform APP714 and isoform APP751 are expressed in several different brain regions including hippocampus, substania nigra pars compacta and cerebellum. In the cerebellum, these isoforms are abundantly expressed in Purkinje cells.
  • DOMAIN: The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.
  • DOMAIN: The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The NPXY site is also involved in clathrin-mediated endocytosis (By similarity).
  • PTM: Proteolytically processed under normal cellular conditions. Cleavage by alpha-secretase or alternatively by beta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, respectively, and the retention of corresponding membrane-anchored C-terminal fragments, C83 and C99. Subsequent processing of C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid beta proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59).
  • PTM: Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-3, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of beta-amyloid peptides (By similarity).
  • PTM: N- and O-glycosylated (By similarity).
  • PTM: Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (By similarity). Phosphorylation on Tyr-757 is required for SHC binding (By similarity).
  • PTM: Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond (By similarity).
  • MISCELLANEOUS: Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. Rat and mouse beta-amyloid peptides have an arginine residue substituted for the bridging histidine residue and are thus less capable of forming amyloid aggegates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding (By similarity).
  • SIMILARITY: Belongs to the APP family.
  • SIMILARITY: Contains 1 BPTI/Kunitz inhibitor domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M18373; AAA37139.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X59379; -; NOT_ANNOTATED_CDS; mRNA.[EMBL / GenBank / DDBJ]
U84012; AAB41502.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
D10603; BAA01456.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC005490; AAH05490.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M24397; AAA39929.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X15210; CAA33280.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U82624; AAB40919.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00114389; -.
IPI00230494; -.
IPI00323079; -.
PIR A27485; A27485.
A32282; A32282.
S04855; S04855.
UniGene Mm.277585
3D structure databases
PDB
2ROZ; NMR; -; A=739-770.[ExPASy / RCSB / EBI]
2YSZ; NMR; -; A=739-770.[ExPASy / RCSB / EBI]
2YT0; NMR; -; A=739-770.[ExPASy / RCSB / EBI]
2YT1; NMR; -; A=739-770.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 2ROZ; -.
2YSZ; -.
2YT0; -.
2YT1; -.
SMR P12023; 28-123, 126-189, 287-342, 460-569.
ModBase P12023.
Protein-protein interaction databases
IntAct P12023; 60.
PTM databases
PhosphoSite P12023; -.
Organism-specific databases
MGI MGI:88059; App.
Gene expression databases
ArrayExpress P12023; -.
Bgee P12023; -.
CleanEx MM_APP; -.
GermOnline ENSMUSG00000022892; Mus musculus.
Ontologies
GO
GO:0045177; Cellular component: apical part of cell (inferred from direct assay from MGI).
GO:0030424; Cellular component: axon (inferred from direct assay from MGI).
GO:0035253; Cellular component: ciliary rootlet (inferred from direct assay from MGI).
GO:0005905; Cellular component: coated pit (inferred from electronic annotation from UniProtKB-SubCell).
GO:0031410; Cellular component: cytoplasmic vesicle (inferred from direct assay from MGI).
GO:0005794; Cellular component: Golgi apparatus (inferred from direct assay from MGI).
GO:0016021; Cellular component: integral to membrane (inferred from direct assay from MGI).
GO:0005624; Cellular component: membrane fraction (inferred from direct assay from MGI).
GO:0031594; Cellular component: neuromuscular junction (inferred from direct assay from MGI).
GO:0048471; Cellular component: perinuclear region of cytoplasm (inferred from direct assay from MGI).
GO:0051233; Cellular component: spindle midzone (inferred from direct assay from MGI).
GO:0005507; Molecular function: copper ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0003677; Molecular function: DNA binding (inferred from direct assay from MGI).
GO:0008201; Molecular function: heparin binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005506; Molecular function: iron ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0004867; Molecular function: serine-type endopeptidase inhibitor activity (inferred from electronic annotation from UniProtKB-KW).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0008344; Biological process: adult locomotory behavior (inferred from mutant phenotype from MGI).
GO:0006915; Biological process: apoptosis (inferred from electronic annotation from UniProtKB-KW).
GO:0008088; Biological process: axon cargo transport (inferred from mutant phenotype from MGI).
GO:0016199; Biological process: axon midline choice point recognition (inferred from mutant phenotype from MGI).
GO:0007155; Biological process: cell adhesion (inferred from electronic annotation from UniProtKB-KW).
GO:0006878; Biological process: cellular copper ion homeostasis (inferred from mutant phenotype from MGI).
GO:0048669; Biological process: collateral sprouting in the absence of injury (inferred from genetic interaction from MGI).
GO:0016358; Biological process: dendrite development (inferred from mutant phenotype from MGI).
GO:0006897; Biological process: endocytosis (inferred from mutant phenotype from MGI).
GO:0030198; Biological process: extracellular matrix organization (inferred from genetic interaction from MGI).
GO:0030900; Biological process: forebrain development (inferred from mutant phenotype from MGI).
GO:0000085; Biological process: G2 phase of mitotic cell cycle (inferred from mutant phenotype from MGI).
GO:0035235; Biological process: ionotropic glutamate receptor signaling pathway (inferred from mutant phenotype from MGI).
GO:0007617; Biological process: mating behavior (inferred from genetic interaction from MGI).
GO:0006378; Biological process: mRNA polyadenylation (inferred from direct assay from MGI).
GO:0050885; Biological process: neuromuscular process controlling balance (inferred from genetic interaction from MGI).
GO:0016322; Biological process: neuron remodeling (inferred from mutant phenotype from MGI).
GO:0007219; Biological process: Notch signaling pathway (inferred from electronic annotation from UniProtKB-KW).
GO:0045931; Biological process: positive regulation of mitotic cell cycle (inferred from mutant phenotype from MGI).
GO:0045944; Biological process: positive regulation of transcription from RNA polymerase II promoter (inferred from direct assay from MGI).
GO:0006468; Biological process: protein amino acid phosphorylation (inferred from mutant phenotype from MGI).
GO:0007176; Biological process: regulation of epidermal growth factor receptor activity (inferred from genetic interaction from MGI).
GO:0040014; Biological process: regulation of multicellular organism growth (inferred from mutant phenotype from MGI).
GO:0050803; Biological process: regulation of synapse structure and activity (inferred from mutant phenotype from MGI).
GO:0006417; Biological process: regulation of translation (inferred from direct assay from MGI).
GO:0051563; Biological process: smooth endoplasmic reticulum calcium ion homeostasis (inferred from genetic interaction from MGI).
GO:0001967; Biological process: suckling behavior (inferred from genetic interaction from MGI).
GO:0051124; Biological process: synaptic growth at neuromuscular junction (inferred from genetic interaction from MGI).
GO:0008542; Biological process: visual learning (inferred from mutant phenotype from MGI).
QuickGo view.
Family and domain databases
InterPro IPR008155; Amyloid_glyco.
IPR013803; Amyloid_glyco_Abeta.
IPR011178; Amyloid_glyco_Cu-bd.
IPR008154; Amyloid_glyco_extra.
IPR019744; Amyloid_glyco_extracell_CS.
IPR015849; Amyloid_glyco_heparin-bd.
IPR019745; Amyloid_glyco_intracell_CS.
IPR019543; APP_amyloid.
IPR002223; Prot_inh_Kunz-m.
Graphical view of domain structure.
Gene3D G3DSA:4.10.230.10; Amyloid_glyco_Abeta; 1.
G3DSA:3.30.1490.140; Amyloid_glyco_Cu-bd; 1.
G3DSA:3.90.570.10; Amyloid_glyco_heparin-bd; 1.
G3DSA:4.10.410.10; Prot_inh_Kunz-m; 1.
Pfam PF02177; A4_EXTRA; 1.
PF10515; APP_amyloid; 1.
PF03494; Beta-APP; 1.
PF00014; Kunitz_BPTI; 1.
Pfam graphical view of domain structure.
PRINTS PR00203; AMYLOIDA4.
PR00204; BETAAMYLOID.
ProDom PD000222; Prot_Inh_Kunz-m; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00006; A4_EXTRA; 1.
SM00131; KU; 1.
SMART graphical view of domain structure.
PROSITE PS00319; A4_EXTRA; 1.
PS00320; A4_INTRA; 1.
PS00280; BPTI_KUNITZ_1; 1.
PS50279; BPTI_KUNITZ_2; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE P12023; -.
Genome annotation databases
Ensembl ENSMUSG00000022892; Mus musculus. [Contig view]
Phylogenomic databases
HOGENOM P12023; -.
HOVERGEN P12023; -.
OMA P12023; QEAANER.
Other
SOURCE App; Mus musculus.
ProtoNet P12023.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Amyloid; Apoptosis; Cell adhesion; Coated pit; Copper; Disulfide bond; Endocytosis; Glycoprotein; Heparin-binding; Iron; Membrane; Metal-binding; Notch signaling pathway; Phosphoprotein; Protease inhibitor; Serine protease inhibitor; Signal; Transmembrane; Zinc.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    17  17     By similarity. 
CHAIN   18   770  753     Amyloid beta A4 protein. PRO_0000000114
CHAIN   18   687  670     Soluble APP-alpha (Potential). PRO_0000000115
CHAIN   18   671  654     Soluble APP-beta (Potential). PRO_0000000116
CHAIN   672   770  99     C99 (By similarity). PRO_0000000117
CHAIN   672   713  42     Beta-amyloid protein 42 (By similarity). PRO_0000000118
CHAIN   672   711  40     Beta-amyloid protein 40 (By similarity). PRO_0000000119
CHAIN   688   770  83     C83 (By similarity). PRO_0000000120
PEPTIDE   688   713  26     P3(42) (By similarity). PRO_0000000121
PEPTIDE   688   711  24     P3(40) (By similarity). PRO_0000000122
CHAIN   712   770  59     Gamma-secretase C-terminal fragment 59. PRO_0000000123
CHAIN   714   770  57     Gamma-secretase C-terminal fragment 57. PRO_0000000124
CHAIN   721   770  50     Gamma-secretase C-terminal fragment 50. PRO_0000000125
CHAIN   740   770  31     C31 (By similarity). PRO_0000000126
TOPO_DOM   18   699  682     Extracellular (Potential). 
TRANSMEM   700   723  24     Potential. 
TOPO_DOM   724   770  47     Cytoplasmic (Potential). 
DOMAIN   291   341  51     BPTI/Kunitz inhibitor. 
REGION   96   110  15     Heparin-binding (By similarity). 
REGION   181   188  8     Zinc-binding (By similarity). 
REGION   391   423  33     Heparin-binding (By similarity). 
REGION   491   522  32     Heparin-binding (By similarity). 
REGION   523   540  18     Collagen-binding (By similarity). 
REGION   732   751  20     Interaction with G(o)-alpha (By similarity). 
MOTIF   724   734  11     Basolateral sorting signal. 
MOTIF   759   762  4     NPXY motif; contains endocytosis signal. 
COMPBIAS   230   260  31     Asp/Glu-rich (acidic). 
COMPBIAS   274   280  7     Poly-Thr. 
METAL   137   137        Copper (By similarity). 
METAL   147   147        Copper (By similarity). 
METAL   149   149        Copper (By similarity). 
METAL   151   151        Copper (Probable). 
METAL   677   677        Copper or zinc (By similarity). 
METAL   685   685        Copper or zinc (By similarity). 
SITE   144   144  1     Required for Cu(2+) reduction (By similarity). 
SITE   301   302  2     Reactive bond (By similarity). 
SITE   671   672  2     Cleavage; by beta-secretase (By similarity). 
SITE   672   673  2     Cleavage; by caspase-6 (By similarity). 
SITE   687   688  2     Cleavage; by alpha-secretase (By similarity). 
SITE   704   704  1     Implicated in free radical propagation (By similarity). 
SITE   706   706  1     Susceptible to oxidation (By similarity). 
SITE   711   712  2     Cleavage; by gamma-secretase; site 1 (By similarity). 
SITE   713   714  2     Cleavage; by gamma-secretase; site 2 (By similarity). 
SITE   720   721  2     Cleavage; by gamma-secretase; site 3 (By similarity). 
SITE   739   740  2     Cleavage; by caspase-6, caspase-8 or caspase-9 (By similarity). 
MOD_RES   198   198        Phosphoserine; by CK2 (By similarity). 
MOD_RES   206   206        Phosphoserine; by CK1 (By similarity). 
MOD_RES   729   729        Phosphothreonine (By similarity). 
MOD_RES   730   730        Phosphoserine; by APP-kinase I (By similarity). 
MOD_RES   743   743        Phosphothreonine; by CDK5 and MAPK10. 
MOD_RES   757   757        Phosphotyrosine (By similarity). 
MOD_RES   762   762        Phosphotyrosine (By similarity). 
CARBOHYD   542   542        N-linked (GlcNAc...) (Probable). 
CARBOHYD   571   571        N-linked (GlcNAc...) (Probable). 
DISULFID   144   158        By similarity. 
DISULFID   291   341        By similarity. 
DISULFID   300   324        By similarity. 
DISULFID   316   337        By similarity. 
VAR_SEQ   289   289        E -> V (in isoform APP695). VSP_000012
VAR_SEQ   290   364        Missing (in isoform APP695). VSP_000013
VAR_SEQ   346   380        Missing (in isoform APP751). VSP_000014
MUTAGEN   728   728        Y->A: No effect on MAPK8IP1 binding. 
MUTAGEN   732   733        HH->GL,GP: Almost complete loss of binding to G(o) alpha subunit. No inhibition of GTPase activity. 
MUTAGEN   743   743        T->E: No effect on MAPK8IP1 binding. 
MUTAGEN   757   757        Y->G: No MAPK8IP1 nor APBA1 nor APBB1 nor DAB1 binding. 
MUTAGEN   759   759        N->A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. 
MUTAGEN   762   762        Y->A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. 
CONFLICT   211   211        G -> V (in Ref. 1; AAA37139). 
CONFLICT   375   375        V -> A (in Ref. 4; AAB41502). 
Sequence information
Length: 770 AA [This is the length of the unprocessed precursor] Molecular weight: 86722 Da [This is the MW of the unprocessed precursor] CRC64: 988D89E089092A3E [This is a checksum on the sequence]
        10         20         30         40         50         60 
MLPSLALLLL AAWTVRALEV PTDGNAGLLA EPQIAMFCGK LNMHMNVQNG KWESDPSGTK 

        70         80         90        100        110        120 
TCIGTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHTH IVIPYRCLVG 

       130        140        150        160        170        180 
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR 

       190        200        210        220        230        240 
GVEFVCCPLA EESDSVDSAD AEEDDSDVWW GGADTDYADG GEDKVVEVAE EEEVADVEEE 

       250        260        270        280        290        300 
EADDDEDVED GDEVEEEAEE PYEEATERTT STATTTTTTT ESVEEVVREV CSEQAETGPC 

       310        320        330        340        350        360 
RAMISRWYFD VTEGKCVPFF YGGCGGNRNN FDTEEYCMAV CGSVSTQSLL KTTSEPLPQD 

       370        380        390        400        410        420 
PDKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA 

       430        440        450        460        470        480 
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL 

       490        500        510        520        530        540 
QAVPPRPHHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER 

       550        560        570        580        590        600 
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET 

       610        620        630        640        650        660 
KTTVELLPVN GEFSLDDLQP WHPFGVDSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN 

       670        680        690        700        710        720 
IKTEEISEVK MDAEFGHDSG FEVRHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL 

       730        740        750        760        770 
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN 

P12023 in FASTA format

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