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P12023 (A4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 179. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Amyloid beta A4 protein
Alternative name(s):
ABPP
Short name=APP
Alzheimer disease amyloid A4 protein homolog
Amyloidogenic glycoprotein
Short name=AG

Cleaved into the following 14 chains:

  1. N-APP
  2. Soluble APP-alpha
    Short name=S-APP-alpha
  3. Soluble APP-beta
    Short name=S-APP-beta
  4. C99
    Alternative name(s):
    APP-C99
  5. Beta-amyloid protein 42
    Alternative name(s):
    Beta-APP42
  6. Beta-amyloid protein 40
    Alternative name(s):
    Beta-APP40
  7. C83
  8. P3(42)
  9. P3(40)
  10. C80
  11. Gamma-secretase C-terminal fragment 59
    Alternative name(s):
    APP-C59
    Amyloid intracellular domain 59
    Short name=AID(59)
    Gamma-CTF(59)
  12. Gamma-secretase C-terminal fragment 57
    Alternative name(s):
    APP-C57
    Amyloid intracellular domain 57
    Short name=AID(57)
    Gamma-CTF(57)
  13. Gamma-secretase C-terminal fragment 50
    Alternative name(s):
    Amyloid intracellular domain 50
    Short name=AID(50)
    Gamma-CTF(50)
  14. C31
Gene names
Name:App
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length770 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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-KAT5 and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity By similarity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV By similarity. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons By similarity. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. Ref.18

Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Binds 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. Also bind GPC1 in lipid rafts By similarity. Ref.18

The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. Ref.18

N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) By similarity. Ref.18

Subunit structure

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. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. 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, TNFRSF21 and AGER By similarity. Interacts with CPEB1. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; this is promoted by heparin binding By similarity. Beta-amyloid protein 40 interacts with S100A9 By similarity. CTF-alpha product of APP interacts with GSAP By similarity. Interacts with SORL1. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20

Subcellular location

Membrane; Single-pass type I membrane protein. Membraneclathrin-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-CTF59 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. Associates with GPC1 in perinuclear compartments. Ref.18

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. Ref.10

Domain

The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.

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.

Post-translational modification

Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and 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-CTF50, gamma-CTF57 and gamma-CTF59 By similarity.

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. Ref.17

N- and O-glycosylated By similarity.

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. Ref.12 Ref.15

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.

Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP) By similarity. Ref.17

Beta-amyloid peptides are degraded by IDE 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 aggregates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding By similarity.

Sequence similarities

Belongs to the APP family.

Contains 1 BPTI/Kunitz inhibitor domain.

Ontologies

Keywords
   Biological processApoptosis
Cell adhesion
Endocytosis
Notch signaling pathway
   Cellular componentAmyloid
Coated pit
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCopper
Heparin-binding
Iron
Metal-binding
Zinc
   Molecular functionProtease inhibitor
Serine protease inhibitor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

adult locomotory behavior

Inferred from mutant phenotype PubMed 10188929PubMed 7758106PubMed 8001115PubMed 9754878. Source: MGI

axon cargo transport

Inferred from mutant phenotype PubMed 11740561. Source: MGI

axon midline choice point recognition

Inferred from mutant phenotype PubMed 8001115. Source: MGI

axonogenesis

Inferred from mutant phenotype PubMed 9390996. Source: MGI

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cellular copper ion homeostasis

Inferred from mutant phenotype PubMed 10526140. Source: MGI

cholesterol metabolic process

Inferred from mutant phenotype PubMed 17920016. Source: MGI

collateral sprouting in absence of injury

Inferred from genetic interaction PubMed 15689559. Source: MGI

dendrite development

Inferred from mutant phenotype PubMed 10188929PubMed 9390996. Source: MGI

endocytosis

Inferred from mutant phenotype PubMed 16025111. Source: MGI

extracellular matrix organization

Inferred from genetic interaction PubMed 15385965. Source: MGI

forebrain development

Inferred from mutant phenotype PubMed 10200318PubMed 8001115. Source: MGI

ionotropic glutamate receptor signaling pathway

Inferred from mutant phenotype PubMed 16025111. Source: MGI

locomotory behavior

Inferred from genetic interaction PubMed 9461064. Source: MGI

mRNA polyadenylation

Inferred from direct assay Ref.19. Source: MGI

mating behavior

Inferred from genetic interaction PubMed 9461064. Source: MGI

negative regulation of neuron differentiation

Inferred from direct assay PubMed 18278038. Source: MGI

neuromuscular process controlling balance

Inferred from genetic interaction PubMed 9461064. Source: MGI

neuron apoptotic process

Inferred from genetic interaction PubMed 16478525. Source: MGI

neuron projection development

Inferred from direct assay PubMed 8083748. Source: MGI

neuron remodeling

Inferred from mutant phenotype PubMed 10219973. Source: MGI

positive regulation of G2/M transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 15561424. Source: MGI

positive regulation of mitotic cell cycle

Inferred from mutant phenotype PubMed 15561424. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15944124. Source: MGI

protein phosphorylation

Inferred from mutant phenotype PubMed 16025111. Source: MGI

regulation of epidermal growth factor-activated receptor activity

Inferred from genetic interaction PubMed 17556541. Source: MGI

regulation of gene expression

Inferred from direct assay PubMed 12074840. Source: MGI

regulation of multicellular organism growth

Inferred from mutant phenotype PubMed 9754878. Source: MGI

regulation of protein binding

Inferred from mutant phenotype PubMed 17920016. Source: MGI

regulation of synapse structure and activity

Inferred from mutant phenotype PubMed 10219973. Source: MGI

regulation of translation

Inferred from direct assay Ref.19. Source: MGI

response to oxidative stress

Inferred from genetic interaction PubMed 16478525. Source: MGI

smooth endoplasmic reticulum calcium ion homeostasis

Inferred from genetic interaction PubMed 12431992. Source: MGI

suckling behavior

Inferred from genetic interaction PubMed 9461064. Source: MGI

synaptic growth at neuromuscular junction

Inferred from genetic interaction PubMed 15689559. Source: MGI

visual learning

Inferred from mutant phenotype PubMed 10338291. Source: MGI

   Cellular_componentER to Golgi transport vesicle

Inferred from direct assay PubMed 19966784. Source: MGI

Golgi apparatus

Inferred from direct assay PubMed 16018997. Source: MGI

apical part of cell

Inferred from direct assay PubMed 15561424. Source: MGI

axon

Inferred from direct assay PubMed 11740561PubMed 15745965. Source: MGI

cell surface

Inferred from electronic annotation. Source: Ensembl

ciliary rootlet

Inferred from direct assay PubMed 16018997. Source: MGI

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 10845772. Source: MGI

cytoplasmic vesicle

Inferred from direct assay PubMed 11740561PubMed 15745965. Source: MGI

dendritic shaft

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from direct assay PubMed 12927782. Source: MGI

membrane

Inferred from direct assay PubMed 10845772PubMed 12927782PubMed 15886206PubMed 9535056. Source: MGI

neuromuscular junction

Inferred from direct assay PubMed 10845772. Source: MGI

neuron projection

Inferred from direct assay PubMed 16301330. Source: MGI

perinuclear region of cytoplasm

Inferred from direct assay PubMed 8207383. Source: MGI

plasma membrane

Inferred from direct assay PubMed 15009636. Source: MGI

receptor complex

Inferred from sequence orthology PubMed 23382219. Source: MGI

spindle midzone

Inferred from direct assay PubMed 15561424. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 15944124. Source: MGI

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidase activator activity

Inferred from electronic annotation. Source: Ensembl

serine-type endopeptidase inhibitor activity

Inferred from electronic annotation. Source: UniProtKB-KW

transition metal ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform APP770 (identifier: P12023-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform APP695 (identifier: P12023-2)

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-364: Missing.
Isoform APP751 (identifier: P12023-3)

The sequence of this isoform differs from the canonical sequence as follows:
     346-380: Missing.
Isoform APP714 (identifier: P12023-4)

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 By similarity
Chain18 – 770753Amyloid beta A4 protein
PRO_0000000114
Chain18 – 687670Soluble APP-alpha Potential
PRO_0000000115
Chain18 – 671654Soluble APP-beta Potential
PRO_0000000116
Chain18 – 286269N-APP By similarity
PRO_0000381968
Chain672 – 77099C99 By similarity
PRO_0000000117
Chain672 – 71342Beta-amyloid protein 42 By similarity
PRO_0000000118
Chain672 – 71140Beta-amyloid protein 40 By similarity
PRO_0000000119
Chain688 – 77083C83 By similarity
PRO_0000000120
Peptide688 – 71326P3(42) By similarity
PRO_0000000121
Peptide688 – 71124P3(40) By similarity
PRO_0000000122
Chain691 – 77080C80
PRO_0000384576
Chain712 – 77059Gamma-secretase C-terminal fragment 59
PRO_0000000123
Chain714 – 77057Gamma-secretase C-terminal fragment 57
PRO_0000000124
Chain721 – 77050Gamma-secretase C-terminal fragment 50
PRO_0000000125
Chain740 – 77031C31 By similarity
PRO_0000000126

Regions

Topological domain18 – 699682Extracellular Potential
Transmembrane700 – 72324Helical; Potential
Topological domain724 – 77047Cytoplasmic Potential
Domain291 – 34151BPTI/Kunitz inhibitor
Region96 – 11015Heparin-binding By similarity
Region181 – 1888Zinc-binding By similarity
Region391 – 42333Heparin-binding By similarity
Region491 – 52232Heparin-binding By similarity
Region523 – 54018Collagen-binding By similarity
Region732 – 75120Interaction with G(o)-alpha By similarity
Region756 – 77015Interaction with DAB2
Motif724 – 73411Basolateral sorting signal
Motif759 – 7624NPXY motif; contains endocytosis signal
Compositional bias230 – 26031Asp/Glu-rich (acidic)
Compositional bias274 – 2807Poly-Thr

Sites

Metal binding1471Copper 1 By similarity
Metal binding1511Copper 1 By similarity
Metal binding1681Copper 1 By similarity
Metal binding6771Copper or zinc 2 By similarity
Metal binding6851Copper or zinc 2 By similarity
Site1441Required for Cu(2+) reduction By similarity
Site301 – 3022Reactive bond By similarity
Site671 – 6722Cleavage; by beta-secretase By similarity
Site672 – 6732Cleavage; by caspase-6 By similarity
Site687 – 6882Cleavage; by alpha-secretase By similarity
Site690 – 6912Cleavage; by theta-secretase By similarity
Site7041Implicated in free radical propagation By similarity
Site7061Susceptible to oxidation By similarity
Site711 – 7122Cleavage; by gamma-secretase; site 1 By similarity
Site713 – 7142Cleavage; by gamma-secretase; site 2 By similarity
Site720 – 7212Cleavage; by gamma-secretase; site 3 By similarity
Site739 – 7402Cleavage; by caspase-6, caspase-8 or caspase-9 By similarity

Amino acid modifications

Modified residue1981Phosphoserine; by CK2 By similarity
Modified residue2061Phosphoserine; by CK1 By similarity
Modified residue7291Phosphothreonine By similarity
Modified residue7301Phosphoserine; by APP-kinase I By similarity
Modified residue7431Phosphothreonine; by CDK5 and MAPK10
Modified residue7571Phosphotyrosine; by ABL1 Ref.12
Glycosylation5421N-linked (GlcNAc...) Probable
Glycosylation5711N-linked (GlcNAc...) Probable
Disulfide bond38 ↔ 62 By similarity
Disulfide bond73 ↔ 117 By similarity
Disulfide bond98 ↔ 105 By similarity
Disulfide bond133 ↔ 187 By similarity
Disulfide bond144 ↔ 174 By similarity
Disulfide bond158 ↔ 186 By similarity
Disulfide bond291 ↔ 341 By similarity
Disulfide bond300 ↔ 324 By similarity
Disulfide bond316 ↔ 337 By similarity

Natural variations

Alternative sequence2891E → V in isoform APP695.
VSP_000012
Alternative sequence290 – 36475Missing in isoform APP695.
VSP_000013
Alternative sequence346 – 38035Missing in isoform APP751.
VSP_000014

Experimental info

Mutagenesis7281Y → A: No effect on MAPK8IP1 binding. Ref.13
Mutagenesis732 – 7332HH → GL or GP: Almost complete loss of binding to G(o) alpha subunit. No inhibition of GTPase activity.
Mutagenesis7431T → E: No effect on MAPK8IP1 binding. Ref.13
Mutagenesis7561G → F, H, N, S or W: Greatly impairs interaction with DAB2. Ref.14
Mutagenesis7561G → Y: Impairs interaction with DAB2. Ref.14
Mutagenesis7571Y → F: Greatly promotes interaction with DAB2. Ref.13 Ref.14
Mutagenesis7571Y → G, H or V: Greatly impairs interaction with DAB2. Ref.13 Ref.14
Mutagenesis7571Y → G: No MAPK8IP1 nor APBA1 nor APBB1 nor DAB1 binding. Ref.13 Ref.14
Mutagenesis7571Y → I or W: Impairs interaction with DAB2. Ref.13 Ref.14
Mutagenesis7591N → A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Ref.13 Ref.14
Mutagenesis7591N → G, L, M or P: Greatly impairs interaction with DAB2. Ref.13 Ref.14
Mutagenesis7601P → E, F, I, K, L, Q, R, V, W or Y: Greatly impairs interaction with DAB2. Ref.14
Mutagenesis7621Y → A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Ref.13 Ref.14
Mutagenesis7621Y → W: Greatly impairs interaction with DAB2. Ref.13 Ref.14
Sequence conflict2111G → V in AAA37139. Ref.1
Sequence conflict3751V → A in AAB41502. Ref.4

Secondary structure

... 770
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform APP770 [UniParc].

Last modified May 9, 2003. Version 3.
Checksum: 988D89E089092A3E

FASTA77086,722
        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 

« Hide

Isoform APP695 [UniParc].

Checksum: 0DE93FA56FB20F3A
Show »

FASTA69578,443
Isoform APP751 [UniParc].

Checksum: BE4D5EC285943E89
Show »

FASTA73582,968
Isoform APP714 (Sequence not available).

References

« Hide 'large scale' references
[1]"Complementary DNA for the mouse homolog of the human amyloid beta protein precursor."
Yamada T., Sasaki H., Furuya H., Miyata T., Goto I., Sakaki Y.
Biochem. Biophys. Res. Commun. 149:665-671(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
Tissue: Brain.
[2]Yamada T.
Submitted (MAR-1988) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"The amyloid beta protein precursor or proteinase nexin II from mouse is closer related to its human homolog than previously reported."
de Strooper B., van Leuven F., van den Berghe H.
Biochim. Biophys. Acta 1129:141-143(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
Strain: BALB/c.
Tissue: Brain.
[4]"Molecular cloning, expression, and regulation of hippocampal amyloid precursor protein of senescence accelerated mouse (SAMP8)."
Kumar V.B., Vyas K., Franko M., Choudhary V., Buddhiraju C., Alvarez J., Morley J.E.
Biochem. Cell Biol. 79:57-67(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
Strain: SAMP8.
Tissue: Hippocampus.
[5]"Positive and negative regulatory elements for the expression of the Alzheimer's disease amyloid precursor-encoding gene in mouse."
Izumi R., Yamada T., Yoshikai S., Sasaki H., Hattori M., Sakai Y.
Gene 112:189-195(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM APP770).
Tissue: Mammary tumor.
[7]"Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer's disease amyloid beta protein precursor."
Yamada T., Sasaki H., Dohura K., Goto I., Sakaki Y.
Biochem. Biophys. Res. Commun. 158:906-912(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-380, ALTERNATIVE SPLICING.
Tissue: Brain and Kidney.
[8]"Sequence of the protease inhibitor domain of the A4 amyloid protein precursor of Mus domesticus."
Fukuchi K., Martin G.M., Deeb S.S.
Nucleic Acids Res. 17:5396-5396(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-364.
Strain: CD-1.
Tissue: Placenta.
[9]"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."
Wragg M.A., Busfield F., Duff K., Korenblat K., Capecchi M., Loring J.F., Goate A.M.
Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 656-737.
Strain: 129/Sv.
[10]"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."
Sola C., Mengod G., Ghetti B., Palacios J.M., Triarhou L.C.
Brain Res. Mol. Brain Res. 17:340-346(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY OF ALTERNATIVE SPLICED FORMS.
[11]"Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I."
Kamal A., Stokin G.B., Yang Z., Xia C.-H., Goldstein L.S.
Neuron 28:449-459(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KNS2.
[12]"The beta-amyloid precursor protein APP is tyrosine-phosphorylated in cells expressing a constitutively active form of the Abl protoncogene."
Zambrano N., Bruni P., Minopoli G., Mosca R., Molino D., Russo C., Schettini G., Sudol M., Russo T.
J. Biol. Chem. 276:19787-19792(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-757.
[13]"C-jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK."
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.
J. Neurosci. 21:6597-6607(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: C-TERMINAL PROTEIN-PROTEIN INTERACTION, MUTAGENESIS OF TYR-728; THR-743; TYR-757; ASN-759 AND TYR-762.
[14]"Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2."
Morris S.M., Cooper J.A.
Traffic 2:111-123(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2, MUTAGENESIS OF GLY-756; TYR-757; ASN-759; PRO-760 AND TYR-762.
[15]"Interaction of Alzheimer's beta-amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade."
Taru H., Iijima K., Hase M., Kirino Y., Yagi Y., Suzuki T.
J. Biol. Chem. 277:20070-20078(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK8IP1, PHOSPHORYLATION.
[16]"The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling."
Roncarati R., Sestan N., Scheinfeld M.H., Berechid B.E., Lopez P.A., Meucci O., McGlade J.C., Rakic P., D'Adamio L.
Proc. Natl. Acad. Sci. U.S.A. 99:7102-7107(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF CTF PEPTIDES WITH NUMB.
[17]"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."
Cupers P., Orlans I., Craessaerts K., Annaert W., De Strooper B.
J. Neurochem. 78:1168-1178(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING BY GAMMA SECRETASE, INTERACTION WITH APBB1.
[18]"The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-nitric oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo."
Cappai R., Cheng F., Ciccotosto G.D., Needham B.E., Masters C.L., Multhaup G., Fransson L.A., Mani K.
J. Biol. Chem. 280:13913-13920(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, FUNCTION.
[19]"Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation."
Cao Q., Huang Y.-S., Kan M.-C., Richter J.D.
Mol. Cell. Biol. 25:10930-10939(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CPEB1.
[20]"Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein."
Andersen O.M., Reiche J., Schmidt V., Gotthardt M., Spoelgen R., Behlke J., von Arnim C.A., Breiderhoff T., Jansen P., Wu X., Bales K.R., Cappai R., Masters C.L., Gliemann J., Mufson E.J., Hyman B.T., Paul S.M., Nykjaer A., Willnow T.E.
Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M18373 mRNA. Translation: AAA37139.1.
X59379 mRNA. No translation available.
U84012 mRNA. Translation: AAB41502.1.
D10603 Genomic DNA. Translation: BAA01456.1.
BC005490 mRNA. Translation: AAH05490.1.
M24397 mRNA. Translation: AAA39929.1.
X15210 mRNA. Translation: CAA33280.1.
U82624 Genomic DNA. Translation: AAB40919.1.
PIRA27485.
A32282.
S04855.
RefSeqNP_001185752.1. NM_001198823.1.
UniGeneMm.277585.
Mm.489029.
Mm.490986.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ROZNMR-A739-770[»]
2YSZNMR-A739-770[»]
2YT0NMR-A739-770[»]
2YT1NMR-A739-770[»]
ProteinModelPortalP12023.
SMRP12023. Positions 26-192, 287-342, 371-566, 686-726, 741-768.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198167. 9 interactions.
IntActP12023. 77 interactions.
MINTMINT-208509.

Protein family/group databases

MEROPSI02.015.

PTM databases

PhosphoSiteP12023.

Proteomic databases

PaxDbP12023.
PRIDEP12023.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000005406; ENSMUSP00000005406; ENSMUSG00000022892. [P12023-2]
GeneID11820.
KEGGmmu:11820.
UCSCuc007ztn.2. mouse. [P12023-1]

Organism-specific databases

CTD351.
MGIMGI:88059. App.

Phylogenomic databases

eggNOGNOG289770.
HOGENOMHOG000232190.
HOVERGENHBG000051.
InParanoidP12023.
KOK04520.
OMATHAHIVI.
OrthoDBEOG7RNJZP.
PhylomeDBP12023.
TreeFamTF317274.

Gene expression databases

ArrayExpressP12023.
BgeeP12023.
CleanExMM_APP.
GenevestigatorP12023.

Family and domain databases

Gene3D3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.230.10. 1 hit.
4.10.410.10. 1 hit.
InterProIPR008155. Amyloid_glyco.
IPR013803. Amyloid_glyco_Abeta.
IPR011178. Amyloid_glyco_Cu-bd.
IPR024329. Amyloid_glyco_E2_domain.
IPR008154. Amyloid_glyco_extra.
IPR019744. Amyloid_glyco_extracell_CS.
IPR015849. Amyloid_glyco_heparin-bd.
IPR019745. Amyloid_glyco_intracell_CS.
IPR028866. APP.
IPR019543. APP_amyloid_C.
IPR002223. Prot_inh_Kunz-m.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PANTHERPTHR23103:SF7. PTHR23103:SF7. 1 hit.
PfamPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
PF03494. Beta-APP. 1 hit.
PF00014. Kunitz_BPTI. 1 hit.
[Graphical view]
PRINTSPR00203. AMYLOIDA4.
PR00759. BASICPTASE.
PR00204. BETAAMYLOID.
SMARTSM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.
[Graphical view]
SUPFAMSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF57362. SSF57362. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
PS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSapp. mouse.
EvolutionaryTraceP12023.
NextBio279717.
PROP12023.
SOURCESearch...

Entry information

Entry nameA4_MOUSE
AccessionPrimary (citable) accession number: P12023
Secondary accession number(s): P97487, P97942, Q99K32
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: May 9, 2003
Last modified: April 16, 2014
This is version 179 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot