Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P08592 (A4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 174. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
  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):
    Gamma-CTF(59)
  12. Gamma-secretase C-terminal fragment 57
    Alternative name(s):
    Gamma-CTF(57)
  13. Gamma-secretase C-terminal fragment 50
    Alternative name(s):
    Gamma-CTF(50)
  14. C31
Gene names
Name:App
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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 By similarity. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb By similarity. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 By similarity. 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 mitochondrial dysfunction in cultured cortical neurons. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1 By similarity.

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 elicits inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also bind GPC1 in lipid rafts By similarity.

Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.

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

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

Subunit structure

Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and NUMB and DAB1 By similarity. Binding to DAB1 inhibits its serine phosphorylation By similarity. 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) By similarity and DDB1. 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. Amyloid beta-42 binds CHRNA7 in hippocampal neurons By similarity. Beta-amyloid associates with HADH2 By similarity. Interacts with CPEB1, ANKS1B, TNFRSF21 and AGER By similarity. 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 By similarity. Ref.10 Ref.11

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). Associates with GPC1 in perinuclear compartments By similarity. 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-742 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Ref.19

Tissue specificity

In the brain, non-L-APP isoforms are expressed in neurons, isoform APP695 being the predominant form. In astrocytes and microglial cells, almost 50% is L-isoform (appican) Ref.8 Ref.9

Developmental stage

From 6 days to 7 months, levels of KPI-containing isoforms increase in the brain cortex and hippocampus. Levels of L-APP increase in all brain regions during the same period, but levels are low compared to non-L-APP isoforms.

Induction

Phosphorylation of mature, glycosylated APP occurs 48-72 hours after treatment of neuronal cells with nerve growth factor which correlates with the timing of neurite outgrowth. Ref.19

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.

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 By similarity. 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.

N-glycosylated. Ref.21

O-glycosylated. O-linkage of chondroitin sulfate to the L-APP isoforms produces the APP proteoglycan core proteins, the appicans. The chondroitin sulfate chain of appicans contains 4-O-sulfated galactose in the linkage region and chondroitin sulfate E in the repeated disaccharide region. Ref.21

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. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin. Ref.17 Ref.18 Ref.19 Ref.20

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.

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.

Mass spectrometry

Molecular mass is 5911.3 Da from positions 721 - 770. Determined by MALDI. Ref.6

Molecular mass is 6024.4 Da from positions 720 - 770. Determined by MALDI. Ref.6

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
Proteoglycan
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

adult locomotory behavior

Inferred from sequence or structural similarity. Source: UniProtKB

axon cargo transport

Inferred from sequence or structural similarity. Source: UniProtKB

axon midline choice point recognition

Inferred from sequence or structural similarity. Source: UniProtKB

axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cellular copper ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol metabolic process

Inferred from electronic annotation. Source: Ensembl

collateral sprouting in absence of injury

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite development

Inferred from sequence or structural similarity. Source: UniProtKB

endocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix organization

Inferred from sequence or structural similarity. Source: UniProtKB

forebrain development

Inferred from electronic annotation. Source: Ensembl

ionotropic glutamate receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

locomotory behavior

Inferred from sequence or structural similarity. Source: UniProtKB

mRNA polyadenylation

Inferred from sequence or structural similarity. Source: UniProtKB

mating behavior

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic G2 phase

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

neuron remodeling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of G2/M transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidase activity

Inferred from direct assay PubMed 12493564. Source: GOC

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of epidermal growth factor-activated receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of multicellular organism growth

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

regulation of synapse structure and activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of translation

Inferred from sequence or structural similarity. Source: UniProtKB

response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

smooth endoplasmic reticulum calcium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

suckling behavior

Inferred from electronic annotation. Source: Ensembl

synaptic growth at neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

visual learning

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

apical part of cell

Inferred from electronic annotation. Source: Ensembl

axon

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from direct assay PubMed 8987743. Source: AgBase

ciliary rootlet

Inferred from electronic annotation. Source: Ensembl

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

dendritic shaft

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from direct assay PubMed 8943215. Source: RGD

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: Ensembl

spindle midzone

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

growth factor receptor binding

Inferred from physical interaction PubMed 19334058. Source: RGD

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidase activator activity

Inferred from direct assay PubMed 12493564. Source: RGD

protein binding

Inferred from physical interaction PubMed 16118793PubMed 9461550. Source: RGD

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 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform APP770 (identifier: P08592-1)

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: P08592-2)

The sequence of this isoform differs from the canonical sequence as follows:
     289-289: E → V
     290-364: Missing.
Isoform L-APP677 (identifier: P08592-3)

The sequence of this isoform is not available.
Note: L-isoforms are referred to as appicans.
Isoform L-APP696 (identifier: P08592-4)

The sequence of this isoform is not available.
Note: L-isoforms are referred to as appicans.
Isoform APP714 (identifier: P08592-5)

The sequence of this isoform is not available.
Isoform L-APP733 (identifier: P08592-6)

The sequence of this isoform is not available.
Note: L-isoforms are referred to as appicans.
Isoform APP751 (identifier: P08592-7)

The sequence of this isoform is not available.
Isoform L-APP752 (identifier: P08592-8)

The sequence of this isoform is not available.
Note: L-isoforms are referred to as appicans.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 By similarity
Chain18 – 770753Amyloid beta A4 protein
PRO_0000000159
Chain18 – 687670Soluble APP-alpha By similarity
PRO_0000000160
Chain18 – 671654Soluble APP-beta Potential
PRO_0000000161
Chain18 – 286269N-APP By similarity
PRO_0000381971
Chain672 – 77099C99 Potential
PRO_0000000162
Chain672 – 71342Beta-amyloid protein 42 By similarity
PRO_0000000163
Chain672 – 71140Beta-amyloid protein 40 By similarity
PRO_0000000164
Chain688 – 77083C83 By similarity
PRO_0000000165
Peptide688 – 71326P3(42) By similarity
PRO_0000000166
Peptide688 – 71124P3(40) By similarity
PRO_0000000167
Chain691 – 77080C80
PRO_0000384579
Chain712 – 77059Gamma-secretase C-terminal fragment 59
PRO_0000000168
Chain714 – 77057Gamma-secretase C-terminal fragment 57
PRO_0000000169
Chain721 – 77050Gamma-secretase C-terminal fragment 50
PRO_0000000170
Chain740 – 77031C31 By similarity
PRO_0000000171

Regions

Topological domain18 – 699682Extracellular Potential
Transmembrane700 – 72324Helical; Potential
Topological domain724 – 77047Cytoplasmic By similarity
Domain291 – 34151BPTI/Kunitz inhibitor
Region96 – 11015Heparin-binding By similarity
Region135 – 15521Copper-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
Motif724 – 73411Basolateral sorting signal By similarity
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
Site687 – 6882Cleavage; by alpha-secretase By similarity
Site690 – 6912Cleavage; by theta-secretase 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
Modified residue7301Phosphoserine; by APP-kinase I Ref.18
Modified residue7431Phosphothreonine; by CDK5 and MAPK10 Ref.20
Modified residue7571Phosphotyrosine; by ABL1 By similarity
Glycosylation5421N-linked (GlcNAc...) Potential
Glycosylation5711N-linked (GlcNAc...) Potential
Glycosylation6561O-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms
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_000015
Alternative sequence290 – 36475Missing in isoform APP695.
VSP_000016

Experimental info

Mutagenesis6561S → A: No chondroitin sulfate linkage to isoform L-APP733. Ref.11 Ref.13
Mutagenesis7041G → V: Little oxidized neuronal proteins. Scarce beta-APP42 peptide aggregation. No neurotoxicity. Ref.11 Ref.16
Mutagenesis732 – 7332HH → GL or GP: Almost complete loss of binding to GNAO1. No inhibition of GTPase activity. Ref.11
Mutagenesis7431T → A: No effect on neurite growth and maturation. Ref.11 Ref.19
Mutagenesis7431T → E: Inhibits neurite growth and maturation. Ref.11 Ref.19
Mutagenesis7571Y → G: No DBB1 binding. Ref.10 Ref.11
Mutagenesis7591N → A: Some DBB1 binding. Ref.10 Ref.11
Mutagenesis7621Y → A: Some DBB1 binding. Ref.10 Ref.11

Secondary structure

.... 770
Helix Strand Turn

Details...

Sequences

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

Last modified December 1, 1992. Version 2.
Checksum: C26C9D6BB2D929A7

FASTA77086,704
        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 EESDSIDSAD AEEDDSDVWW GGADTDYADG GEDKVVEVAE EEEVADVEEE 

       250        260        270        280        290        300 
EAEDDEDVED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC 

       310        320        330        340        350        360 
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVSSQSLL KTTSEPLPQD 

       370        380        390        400        410        420 
PVKLPTTAAS 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: 61D21E1E941972DC
Show »

FASTA69578,483
Isoform L-APP677 (Sequence not available).
Isoform L-APP696 (Sequence not available).
Isoform APP714 (Sequence not available).
Isoform L-APP733 (Sequence not available).
Isoform APP751 (Sequence not available).
Isoform L-APP752 (Sequence not available).

References

[1]"Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact."
Shivers B.D., Hilbich C., Multhaup G., Salbaum J.M., Beyreuther K., Seeburg P.H.
EMBO J. 7:1365-1370(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
Tissue: Brain.
[2]"A new beta amyloid precursor protein cDNA found in Rat6 embryo fibroblasts."
Feng J., Song S., Zheng J.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP770).
[3]"Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein."
Schubert D., Schroeder R., LaCorbiere M., Saitoh T., Cole G.
Science 241:223-226(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-44.
[4]"Purification and tissue level of the beta-amyloid peptide precursor of rat brain."
Potempska A., Styles J., Mehta P., Kim K.S., Miller D.L.
J. Biol. Chem. 266:8464-8469(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-32.
[5]"The sequence of the two extra exons in rat preA4."
Kang J., Mueller-Hill B.
Nucleic Acids Res. 17:2130-2130(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-364.
Tissue: Liver.
[6]"Distinct intramembrane cleavage of the beta-amyloid precursor protein family resembling gamma-secretase-like cleavage of Notch."
Gu Y., Misonou H., Sato T., Dohmae N., Takio K., Ihara Y.
J. Biol. Chem. 276:35235-35238(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 720-730, MASS SPECTROMETRY.
[7]"APP gene family. Alternative splicing generates functionally related isoforms."
Sandbrink R., Masters C.L., Beyreuther K.
Ann. N. Y. Acad. Sci. 777:281-287(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[8]"The Alzheimer amyloid precursor proteoglycan (appican) is present in brain and is produced by astrocytes but not by neurons in primary neural cultures."
Shioi J., Pangalos M.N., Ripellino J.A., Vassilacopoulou D., Mytilineou C., Margolis R.U., Robakis N.K.
J. Biol. Chem. 270:11839-11844(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY OF APPICAN.
[9]"Expression of the APP gene family in brain cells, brain development and aging."
Sandbrink R., Monning U., Masters C.L., Beyreuther K.
Gerontology 43:119-131(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY OF ISOFORMS.
[10]"A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein."
Watanabe T., Sukegawa J., Tomita S., Iijima K., Oguchi S., Suzuki T., Nairn A.C., Greengard P.
J. Neurochem. 72:549-556(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDB1, MUTAGENESIS OF TYR-757; ASN-759 AND TYR-762.
[11]"The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction."
Brouillet E., Trembleau A., Galanaud D., Volovitch M., Bouillot C., Valenza C., Prochiantz A., Allinquant B.
J. Neurosci. 19:1717-1727(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNAO1, MUTAGENESIS OF 732-HIS-HIS-733.
[12]"The beta A4 amyloid precursor protein binding to copper."
Hesse L., Beher D., Masters C.L., Multhaup G.
FEBS Lett. 349:109-116(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: COPPER-BINDING.
[13]"The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene."
Pangalos M.N., Efthimiopoulos S., Shioi J., Robakis N.K.
J. Biol. Chem. 270:10388-10391(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERISTICS OF APPICAN, MUTAGENESIS OF SER-656.
[14]"The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction."
Huang X., Atwood C.S., Hartshorn M.A., Multhaup G., Goldstein L.E., Scarpa R.C., Cuajungco M.P., Gray D.N., Lim J., Moir R.D., Tanzi R.E., Bush A.I.
Biochemistry 38:7609-7616(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: BETA-AMYLOID METAL-BINDING.
[15]"Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease."
Liu S.T., Howlett G., Barrow C.J.
Biochemistry 38:9373-9378(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: BETA-AMYLOID ZINC-BINDING.
[16]"Role of glycine-33 and methionine-35 in Alzheimer's amyloid beta-peptide 1-42-associated oxidative stress and neurotoxicity."
Kanski J., Varadarajan S., Aksenova M., Butterfield D.A.
Biochim. Biophys. Acta 1586:190-198(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: IMPORTANCE OF GLY-704 IN FREE RADICAL PROPAGATION, MUTAGENESIS OF GLY-704.
[17]"The cytoplasmic domain of Alzheimer's amyloid precursor protein is phosphorylated at Thr654, Ser655, and Thr668 in adult rat brain and cultured cells."
Oishi M., Nairn A.C., Czernik A.J., Lim G.S., Isohara T., Gandy S.E., Greengard P., Suzuki T.
Mol. Med. 3:111-123(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[18]"Phosphorylation of the cytoplasmic domain of Alzheimer's beta-amyloid precursor protein at Ser655 by a novel protein kinase."
Isohara T., Horiuchi A., Watanabe T., Ando K., Czernik A.J., Uno I., Greengard P., Nairn A.C., Suzuki T.
Biochem. Biophys. Res. Commun. 258:300-305(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-730.
[19]"Role of phosphorylation of Alzheimer's amyloid precursor protein during neuronal differentiation."
Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C., Kirino Y., Greengard P., Suzuki T.
J. Neurosci. 19:4421-4427(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INDUCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-743.
[20]"Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5."
Iijima K., Ando K., Takeda S., Satoh Y., Seki T., Itohara S., Greengard P., Kirino Y., Nairn A.C., Suzuki T.
J. Neurochem. 75:1085-1091(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-743.
[21]"Appican, the proteoglycan form of the amyloid precursor protein, contains chondroitin sulfate E in the repeating disaccharide region and 4-O-sulfated galactose in the linkage region."
Tsuchida K., Shioi J., Yamada S., Boghosian G., Wu A., Cai H., Sugahara K., Robakis N.K.
J. Biol. Chem. 276:37155-37160(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATE IN APPICAN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07648 mRNA. Translation: CAA30488.1.
AF513015 mRNA. Translation: AAM90259.1.
X14066 mRNA. Translation: CAA32229.1.
PIRS00550.
S03607.
S23094.
RefSeqNP_062161.1. NM_019288.2. [P08592-1]
XP_006248073.1. XM_006248011.1. [P08592-2]
UniGeneRn.2104.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M7EX-ray2.45D/E/F755-763[»]
1NMJNMR-A672-699[»]
1OQNX-ray2.30C/D755-763[»]
ProteinModelPortalP08592.
SMRP08592. Positions 28-189, 287-342, 374-565, 672-699, 739-770.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248450. 2 interactions.
DIPDIP-6114N.
DIP-618N.
DIP-685N.
IntActP08592. 7 interactions.
MINTMINT-1521802.

Protein family/group databases

MEROPSI02.015.
TCDB1.C.50.1.1. the amyloid -protein peptide (app) family.

PTM databases

PhosphoSiteP08592.

Proteomic databases

PaxDbP08592.
PRIDEP08592.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000044081; ENSRNOP00000040243; ENSRNOG00000006997. [P08592-2]
ENSRNOT00000048854; ENSRNOP00000041613; ENSRNOG00000006997. [P08592-1]
GeneID54226.
KEGGrno:54226.
UCSCRGD:2139. rat. [P08592-1]

Organism-specific databases

CTD351.
RGD2139. App.

Phylogenomic databases

eggNOGNOG289770.
GeneTreeENSGT00530000063252.
HOGENOMHOG000232190.
HOVERGENHBG000051.
InParanoidP08592.
KOK04520.
OMATHAHIVI.
OrthoDBEOG7RNJZP.
PhylomeDBP08592.
TreeFamTF317274.

Gene expression databases

GenevestigatorP08592.

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

EvolutionaryTraceP08592.
NextBio610648.
PROP08592.

Entry information

Entry nameA4_RAT
AccessionPrimary (citable) accession number: P08592
Secondary accession number(s): Q547B7
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: December 1, 1992
Last modified: July 9, 2014
This is version 174 of the entry and version 2 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