Amyloid beta A4 protein precursor - Mus musculus (Mouse)

Preferred order of sections

Names and origin

Protein names

Recommended 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:

N-APP
Soluble APP-alpha
Short name=S-APP-alpha
Soluble APP-beta
Short name=S-APP-beta
C99
Alternative name(s):
APP-C99
Beta-amyloid protein 42
Alternative name(s):
Beta-APP42
Beta-amyloid protein 40
Alternative name(s):
Beta-APP40
C83
P3(42)
P3(40)
C80
Gamma-secretase C-terminal fragment 59
Alternative name(s):
APP-C59
Amyloid intracellular domain 59
Short name=AID(59)
Gamma-CTF(59)
Gamma-secretase C-terminal fragment 57
Alternative name(s):
APP-C57
Amyloid intracellular domain 57
Short name=AID(57)
Gamma-CTF(57)
Gamma-secretase C-terminal fragment 50
Alternative name(s):
Amyloid intracellular domain 50
Short name=AID(50)
Gamma-CTF(50)
C31

Gene names

Name:

App

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	770 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19
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-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 aggegates. 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 process	Apoptosis Cell adhesion Endocytosis Notch signaling pathway
Cellular component	Amyloid Coated pit Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Ligand	Copper Heparin-binding Iron Metal-binding Zinc
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2 phase of mitotic cell cycle Inferred from mutant phenotype PubMed 15561424. Source: MGI Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW adult locomotory behavior Inferred from mutant phenotype PubMed 10188929 PubMed 7758106 PubMed 8001115 PubMed 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 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 10188929 PubMed 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 10200318 PubMed 8001115. Source: MGI induction of apoptosis Inferred from electronic annotation. Source: Compara ionotropic glutamate receptor signaling pathway Inferred from mutant phenotype PubMed 16025111. 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 remodeling Inferred from mutant phenotype PubMed 10219973. 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 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_component	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 11740561 PubMed 15745965. Source: MGI cell surface Inferred from electronic annotation. Source: Compara ciliary rootlet Inferred from direct assay PubMed 16018997. Source: MGI coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle Inferred from direct assay PubMed 11740561 PubMed 15745965. Source: MGI dendritic shaft Inferred from electronic annotation. Source: Compara dendritic spine Inferred from electronic annotation. Source: Compara integral to membrane Inferred from direct assay PubMed 12927782. Source: MGI neuromuscular junction Inferred from direct assay PubMed 10845772. Source: MGI perinuclear region of cytoplasm Inferred from direct assay PubMed 8207383. Source: MGI plasma membrane Inferred from direct assay PubMed 15009636. Source: MGI spindle midzone Inferred from direct assay PubMed 15561424. Source: MGI
Molecular_function	DNA 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: Compara 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Apba2	P98084	2	EBI-78814,EBI-81669
Apbb1	Q9QXJ1	2	EBI-78814,EBI-81338
Aplp1	Q03157	4	EBI-78814,EBI-399929
Aplp2	Q06335	3	EBI-78814,EBI-446708
Dab1	P97318	3	EBI-78814,EBI-81680
Lingo1	Q9D1T0	2	EBI-78814,EBI-2012981
MAPK8IP1	Q9UQF2	2	EBI-78814,EBI-78404	From a different organism.
Mapk8ip1	Q9WVI9	3	EBI-78814,EBI-74515
Mapk8ip1	Q9WVI9-1	3	EBI-78814,EBI-288461
Shc3	Q61120	2	EBI-78814,EBI-79107
Slc40a1	Q9JHI9	2	EBI-78814,EBI-2931424

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

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

18 – 286

269

N-APP By similarity

PRO_0000381968

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

691 – 770

80

C80

PRO_0000384576

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

Regions

Topological domain

18 – 699

682

Extracellular Potential

Transmembrane

700 – 723

24

Helical; Potential

Topological domain

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

Region

756 – 770

15

Interaction with DAB2

Motif

724 – 734

11

Basolateral sorting signal

Motif

759 – 762

4

NPXY motif; contains endocytosis signal

Compositional bias

230 – 260

31

Asp/Glu-rich (acidic)

Compositional bias

274 – 280

7

Poly-Thr

Sites

Metal binding

147

1

Copper 1 By similarity

Metal binding

151

1

Copper 1 By similarity

Metal binding

168

1

Copper 1 By similarity

Metal binding

677

1

Copper or zinc 2 By similarity

Metal binding

685

1

Copper or zinc 2 By similarity

Site

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

690 – 691

2

Cleavage; by theta-secretase By similarity

Site

704

1

Implicated in free radical propagation By similarity

Site

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

Amino acid modifications

Modified residue

198

1

Phosphoserine; by CK2 By similarity

Modified residue

206

1

Phosphoserine; by CK1 By similarity

Modified residue

729

1

Phosphothreonine By similarity

Modified residue

730

1

Phosphoserine; by APP-kinase I By similarity

Modified residue

743

1

Phosphothreonine; by CDK5 and MAPK10

Modified residue

757

1

Phosphotyrosine; by ABL1 Ref.12

Glycosylation

542

1

N-linked (GlcNAc...) Probable

Glycosylation

571

1

N-linked (GlcNAc...) Probable

Disulfide bond

38 ↔ 62

By similarity

Disulfide bond

73 ↔ 117

By similarity

Disulfide bond

98 ↔ 105

By similarity

Disulfide bond

133 ↔ 187

By similarity

Disulfide bond

144 ↔ 174

By similarity

Disulfide bond

158 ↔ 186

By similarity

Disulfide bond

291 ↔ 341

By similarity

Disulfide bond

300 ↔ 324

By similarity

Disulfide bond

316 ↔ 337

By similarity

Natural variations

Alternative sequence

289

1

E → V in isoform APP695.

VSP_000012

Alternative sequence

290 – 364

75

Missing in isoform APP695.

VSP_000013

Alternative sequence

346 – 380

35

Missing in isoform APP751.

VSP_000014

Experimental info

Mutagenesis

728

1

Y → A: No effect on MAPK8IP1 binding. Ref.13

Mutagenesis

732 – 733

2

HH → GL or GP: Almost complete loss of binding to G(o) alpha subunit. No inhibition of GTPase activity.

Mutagenesis

743

1

T → E: No effect on MAPK8IP1 binding. Ref.13

Mutagenesis

756

1

G → F, H, N, S or W: Greatly impairs interaction with DAB2. Ref.14

Mutagenesis

756

1

G → Y: Impairs interaction with DAB2. Ref.14

Mutagenesis

757

1

Y → F: Greatly promotes interaction with DAB2. Ref.13 Ref.14

Mutagenesis

757

1

Y → G, H or V: Greatly impairs interaction with DAB2. Ref.13 Ref.14

Mutagenesis

757

1

Y → G: No MAPK8IP1 nor APBA1 nor APBB1 nor DAB1 binding. Ref.13 Ref.14

Mutagenesis

757

1

Y → I or W: Impairs interaction with DAB2. Ref.13 Ref.14

Mutagenesis

759

1

N → A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Ref.13 Ref.14

Mutagenesis

759

1

N → G, L, M or P: Greatly impairs interaction with DAB2. Ref.13 Ref.14

Mutagenesis

760

1

P → E, F, I, K, L, Q, R, V, W or Y: Greatly impairs interaction with DAB2. Ref.14

Mutagenesis

762

1

Y → A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Ref.13 Ref.14

Mutagenesis

762

1

Y → W: Greatly impairs interaction with DAB2. Ref.13 Ref.14

Sequence conflict

211

1

G → V in AAA37139. Ref.1

Sequence conflict

375

1

V → A in AAB41502. Ref.4

Secondary structure

1

.

770

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Isoform APP770 [UniParc].

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

FASTA

770

86,722

        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 »

FASTA

695

78,443

Isoform APP751 [UniParc].

Checksum: BE4D5EC285943E89
Show »

FASTA

735

82,968

Isoform APP714 (Sequence not available).

–

References

	« Hide 'large scale' referencesShow '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.
+	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.

IPI

IPI00114389.
IPI00230494.
IPI00323079.

PIR

A27485.
A32282.
S04855.

RefSeq

NP_001185752.1. NM_001198823.1.

UniGene

Mm.277585.
Mm.489029.
Mm.490986.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ROZ	NMR	-	A	739-770	[»]
2YSZ	NMR	-	A	739-770	[»]
2YT0	NMR	-	A	739-770	[»]
2YT1	NMR	-	A	739-770	[»]

ProteinModelPortal

P12023.

SMR

P12023. Positions 26-192, 287-342, 371-566, 686-726, 741-768.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12023. 71 interactions.

MINT

MINT-208509.

Protein family/group databases

MEROPS

I02.015.

PTM databases

PhosphoSite

P12023.

Proteomic databases

PaxDb

P12023.

PRIDE

P12023.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000005406; ENSMUSP00000005406; ENSMUSG00000022892.

GeneID

11820.

KEGG

mmu:11820.

UCSC

uc007ztn.2. mouse.

Organism-specific databases

CTD

351.

MGI

MGI:88059. App.

Phylogenomic databases

eggNOG

NOG289770.

HOGENOM

HOG000232190.

HOVERGEN

HBG000051.

InParanoid

P12023.

KO

K04520.

OMA

THAHIVI.

OrthoDB

EOG45B1F4.

Gene expression databases

ArrayExpress

P12023.

Bgee

P12023.

CleanEx

MM_APP.

Genevestigator

P12023.

GermOnline

ENSMUSG00000022892. Mus musculus.

Family and domain databases

Gene3D

3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.230.10. 1 hit.
4.10.410.10. 1 hit.

InterPro

IPR008155. 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.
IPR019543. APP_amyloid_C.
IPR002223. Prot_inh_Kunz-m.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]

Pfam

PF10515. 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]

PRINTS

PR00203. AMYLOIDA4.
PR00759. BASICPTASE.
PR00204. BETAAMYLOID.

SMART

SM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.
[Graphical view]

SUPFAM

SSF56491. A4_extra. 1 hit.
SSF89811. Amyloid_glyco_Cu-bd. 1 hit.
SSF57362. Prot_inh_Kunz-m. 1 hit.
SSF109843. SSF109843. 1 hit.

PROSITE

PS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
PS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

app. mouse.

EvolutionaryTrace

P12023.

NextBio

279717.

SOURCE

Search...

Entry information

Entry name

A4_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 171 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Cleaved into the following 14 chains:

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents