Reviewed, UniProtKB/Swiss-Prot P12023 (A4_MOUSE)

Names and origin

Protein names

Recommended name:
    Amyloid beta A4 protein
Alternative name(s):
    Alzheimer disease amyloid A4 protein homolog
    ABPP
      Short name=APP
    Amyloidogenic glycoprotein
      Short name=AG
Cleaved into the following 12 chains:
    1- Recommended name:
            Soluble APP-alpha
                Short name=S-APP-alpha
    2- Recommended name:
            Soluble APP-beta
                Short name=S-APP-beta
    3- Recommended name:
            C99
        Alternative name(s):
            APP-C99
    4- Recommended name:
            Beta-amyloid protein 42
        Alternative name(s):
            Beta-APP42
    5- Recommended name:
            Beta-amyloid protein 40
        Alternative name(s):
            Beta-APP40
    6- Recommended name:
            C83
    7- Recommended name:
            P3(42)
    8- Recommended name:
            P3(40)
    9- Recommended name:
            Gamma-secretase C-terminal fragment 59
        Alternative name(s):
            Gamma-CTF(59)
            Amyloid intracellular domain 59
              Short name=AID(59)
            APP-C59
    10- Recommended name:
            Gamma-secretase C-terminal fragment 57
        Alternative name(s):
            Gamma-CTF(57)
            Amyloid intracellular domain 57
              Short name=AID(57)
            APP-C57
    11- Recommended name:
            Gamma-secretase C-terminal fragment 50
        Alternative name(s):
            Gamma-CTF(50)
            Amyloid intracellular domain 50
              Short name=AID(50)
    12- Recommended name:
            C31

Gene names

Name:

App

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › 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-HTATIP and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity By similarity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV By similarity. The splice isoforms that contain the BPTI domain possess protease inhibitor activity By similarity. Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. Rat and mouse beta-amyloid peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation By similarity. The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
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. Also interacts with GPCR-like protein BPP, FPRL1, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1 By similarity. In vitro, it binds MAPT via the MT-binding domains By similarity. Associates with microtubules in the presence of ATP and in a kinesin-dependent manner By similarity. Interacts, through a C-terminal domain, with GNAO1 By similarity. Amyloid beta-42 binds CHRNA7 in hippocampal neurons By similarity. Beta-amyloid associates with HADH2 By similarity. Interacts with ANKS1B By similarity. Interacts with CPEB1.
Subcellular location	Membrane; Single-pass type I membrane protein. Membrane › clathrin-coated pit. Note: Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FPRL1 at the cell surface and the complex is then rapidly internalized By similarity. APP sorts to the basolateral surface in epithelial cells By similarity. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment By similarity.
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 by alpha-secretase or alternatively by beta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, respectively, and the retention of corresponding membrane-anchored C-terminal fragments, C83 and C99. Subsequent processing of C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid beta proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). 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. 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. Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond By similarity.
Miscellaneous	Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. Rat and mouse beta-amyloid peptides have an arginine residue substituted for the bridging histidine residue and are thus less capable of forming amyloid aggegates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding By similarity.
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
Ligand	Copper Heparin-binding Iron Metal-binding Zinc
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G2 phase of mitotic cell cycle Inferred from mutant phenotype. Source: MGI Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW adult locomotory behavior Inferred from mutant phenotype. Source: MGI apoptosis Inferred from electronic annotation. Source: UniProtKB-KW axon cargo transport Inferred from mutant phenotype. Source: MGI axon midline choice point recognition Inferred from mutant phenotype. Source: MGI cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cellular copper ion homeostasis Inferred from mutant phenotype. Source: MGI collateral sprouting in the absence of injury Inferred from genetic interaction. Source: MGI dendrite development Inferred from mutant phenotype. Source: MGI endocytosis Inferred from mutant phenotype. Source: MGI extracellular matrix organization Inferred from genetic interaction. Source: MGI forebrain development Inferred from mutant phenotype. Source: MGI ionotropic glutamate receptor signaling pathway Inferred from mutant phenotype. Source: MGI mRNA polyadenylation Ref.16 Inferred from direct assay. Source: MGI mating behavior Inferred from genetic interaction. Source: MGI neuromuscular process controlling balance Inferred from genetic interaction. Source: MGI neuron remodeling Inferred from mutant phenotype. Source: MGI positive regulation of mitotic cell cycle Inferred from mutant phenotype. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI protein amino acid phosphorylation Inferred from mutant phenotype. Source: MGI regulation of epidermal growth factor receptor activity Inferred from genetic interaction. Source: MGI regulation of multicellular organism growth Inferred from mutant phenotype. Source: MGI regulation of synapse structure and activity Inferred from mutant phenotype. Source: MGI regulation of translation Ref.16 Inferred from direct assay. Source: MGI smooth endoplasmic reticulum calcium ion homeostasis Inferred from genetic interaction. Source: MGI suckling behavior Inferred from genetic interaction. Source: MGI synaptic growth at neuromuscular junction Inferred from genetic interaction. Source: MGI visual learning Inferred from mutant phenotype. Source: MGI
Cellular component	Golgi apparatus Inferred from direct assay. Source: MGI apical part of cell Inferred from direct assay. Source: MGI axon Inferred from direct assay. Source: MGI ciliary rootlet Inferred from direct assay. Source: MGI coated pit Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle Inferred from direct assay. Source: MGI integral to membrane Inferred from direct assay. Source: MGI membrane fraction Inferred from direct assay. Source: MGI neuromuscular junction Inferred from direct assay. Source: MGI perinuclear region of cytoplasm Inferred from direct assay. Source: MGI spindle midzone Inferred from direct assay. Source: MGI
Molecular function	DNA binding Inferred from direct assay. Source: MGI copper ion binding Inferred from electronic annotation. Source: UniProtKB-KW heparin binding Inferred from electronic annotation. Source: UniProtKB-KW iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.12 Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P35331	1	EBI-286828,EBI-2028081	From a different organism.
Apba2	P98084	1	EBI-78814,EBI-81669
Apbb1	Q9QXJ1	1	EBI-78814,EBI-81338
Aplp1	Q03157	2	EBI-78814,EBI-399929
Aplp2	Q06335	1	EBI-78814,EBI-446708
CNTN3	Q9P232	1	EBI-286828,EBI-2028361	From a different organism.
CNTN4	Q8IWV2	1	EBI-286828,EBI-2028276	From a different organism.
Dab1	P97318	1	EBI-78814,EBI-81680
Lingo1	Q9D1T0	1	EBI-78814,EBI-2012981
MAPK8IP1	Q9UQF2	1	EBI-78814,EBI-78404	From a different organism.
MAPK8IP1	Q9UQF2	1	EBI-286828,EBI-78404	From a different organism.
Mapk8ip1	Q9WVI9	2	EBI-78814,EBI-74515
Mapk8ip1	Q9WVI9-1	2	EBI-78814,EBI-288461
Mapk8ip1	Q9WVI9-1	1	EBI-286828,EBI-288461
Shc3	Q61120	1	EBI-78814,EBI-79107

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	672 – 770	99	C99 By similarity		PRO_0000000117
	Chain	672 – 713	42	Beta-amyloid protein 42 By similarity		PRO_0000000118
	Chain	672 – 711	40	Beta-amyloid protein 40 By similarity		PRO_0000000119
	Chain	688 – 770	83	C83 By similarity		PRO_0000000120
	Peptide	688 – 713	26	P3(42) By similarity		PRO_0000000121
	Peptide	688 – 711	24	P3(40) By similarity		PRO_0000000122
	Chain	712 – 770	59	Gamma-secretase C-terminal fragment 59		PRO_0000000123
	Chain	714 – 770	57	Gamma-secretase C-terminal fragment 57		PRO_0000000124
	Chain	721 – 770	50	Gamma-secretase C-terminal fragment 50		PRO_0000000125
	Chain	740 – 770	31	C31 By similarity		PRO_0000000126
Regions
	Topological domain	18 – 699	682	Extracellular Potential
	Transmembrane	700 – 723	24	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
	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	137	1	Copper By similarity
	Metal binding	147	1	Copper By similarity
	Metal binding	149	1	Copper By similarity
	Metal binding	151	1	Copper Probable
	Metal binding	677	1	Copper or zinc By similarity
	Metal binding	685	1	Copper or zinc 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	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 similarity
	Modified residue	762	1	Phosphotyrosine By similarity
	Glycosylation	542	1	N-linked (GlcNAc...) Probable
	Glycosylation	571	1	N-linked (GlcNAc...) Probable
	Disulfide bond	144 ↔ 158		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.12
	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.12
	Mutagenesis	757	1	Y → G: No MAPK8IP1 nor APBA1 nor APBB1 nor DAB1 binding. Ref.12
	Mutagenesis	759	1	N → A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Ref.12
	Mutagenesis	762	1	Y → A: No MAPK8IP1 nor APBA1 nor Dab1 binding. No effect on APBB1 binding. Ref.12
	Sequence conflict	211	1	G → V in AAA37139. Ref.1
	Sequence conflict	375	1	V → A in AAB41502. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform APP770 [UniParc]. Last modified May 9, 2003. Version 3. Checksum: 988D89E089092A3E	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
	Isoform APP695. Checksum: 0DE93FA56FB20F3A	FASTA	695	78,443
	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 ESVEEVVRVP TTAASTPDAV 310 320 330 340 350 360 DKYLETPGDE NEHAHFQKAK ERLEAKHRER MSQVMREWEE AERQAKNLPK ADKKAVIQHF 370 380 390 400 410 420 QEKVESLEQE AANERQQLVE THMARVEAML NDRRRLALEN YITALQAVPP RPHHVFNMLK 430 440 450 460 470 480 KYVRAEQKDR QHTLKHFEHV RMVDPKKAAQ IRSQVMTHLR VIYERMNQSL SLLYNVPAVA 490 500 510 520 530 540 EEIQDEVDEL LQKEQNYSDD VLANMISEPR ISYGNDALMP SLTETKTTVE LLPVNGEFSL 550 560 570 580 590 600 DDLQPWHPFG VDSVPANTEN EVEPVDARPA ADRGLTTRPG SGLTNIKTEE ISEVKMDAEF 610 620 630 640 650 660 GHDSGFEVRH QKLVFFAEDV GSNKGAIIGL MVGGVVIATV IVITLVMLKK KQYTSIHHGV 670 680 690 VEVDAAVTPE ERHLSKMQQN GYENPTYKFF EQMQN
	Isoform APP751. Checksum: BE4D5EC285943E89	FASTA	735	82,968
	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 CGSVSTPGDE NEHAHFQKAK 370 380 390 400 410 420 ERLEAKHRER MSQVMREWEE AERQAKNLPK ADKKAVIQHF QEKVESLEQE AANERQQLVE 430 440 450 460 470 480 THMARVEAML NDRRRLALEN YITALQAVPP RPHHVFNMLK KYVRAEQKDR QHTLKHFEHV 490 500 510 520 530 540 RMVDPKKAAQ IRSQVMTHLR VIYERMNQSL SLLYNVPAVA EEIQDEVDEL LQKEQNYSDD 550 560 570 580 590 600 VLANMISEPR ISYGNDALMP SLTETKTTVE LLPVNGEFSL DDLQPWHPFG VDSVPANTEN 610 620 630 640 650 660 EVEPVDARPA ADRGLTTRPG SGLTNIKTEE ISEVKMDAEF GHDSGFEVRH QKLVFFAEDV 670 680 690 700 710 720 GSNKGAIIGL MVGGVVIATV IVITLVMLKK KQYTSIHHGV VEVDAAVTPE ERHLSKMQQN 730 GYENPTYKFF EQMQN
	Isoform APP714 (Sequence not available).	FASTA	–	–

References

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[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: 3322280] [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: 1756177] [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: 11235921] [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: 1555768] [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: 15489334] [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: 2493250] [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: 2569710] [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 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: 8510506] [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: 11144355] [Abstract] Cited for: INTERACTION WITH KNS2.
[12]	"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: 11517249] [Abstract] Cited for: C-TERMINAL PROTEIN-PROTEIN INTERACTION, MUTAGENESIS OF TYR-728; THR-743; TYR-757; ASN-759 AND TYR-762.
[13]	"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: 11912189] [Abstract] Cited for: INTERACTION WITH MAPK8IP1, PHOSPHORYLATION.
[14]	"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: 12011466] [Abstract] Cited for: INTERACTION OF CTF PEPTIDES WITH NUMB.
[15]	"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: 11553691] [Abstract] Cited for: PROTEOLYTIC PROCESSING BY GAMMA SECRETASE, INTERACTION WITH APBB1.
[16]	"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: 16314516] [Abstract] Cited for: INTERACTION WITH CPEB1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Mm.277585

3D structure databases

PDBPDBe

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	[»]

SMR

P12023. Positions 28-123, 126-189, 287-342, 460-569.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12023. 60 interactions.

PTM databases

PhosphoSite

P12023.

Proteomic databases

PRIDE

P12023.

Genome annotation databases

Ensembl

ENSMUSG00000022892. Mus musculus. [Contig view]

Organism-specific databases

MGI

MGI:88059. App.

Phylogenomic databases

HOGENOM

P12023.

HOVERGEN

P12023.

OMA

P12023. QEAANER.

Gene expression databases

ArrayExpress

P12023.

Bgee

P12023.

CleanEx

MM_APP.

GermOnline

ENSMUSG00000022892. Mus musculus.

Family and domain databases

InterPro

IPR008155. Amyloid_glyco.
IPR013803. Amyloid_glyco_Abeta.
IPR011178. Amyloid_glyco_Cu-bd.
IPR008154. Amyloid_glyco_extra.
IPR019744. Amyloid_glyco_extracell_CS.
IPR015849. Amyloid_glyco_heparin-bd.
IPR019745. Amyloid_glyco_intracell_CS.
IPR019543. APP_amyloid.
IPR002223. Prot_inh_Kunz-m.
[Graphical view]

Gene3D

G3DSA:4.10.230.10. Amyloid_glyco_Abeta. 1 hit.
G3DSA:3.30.1490.140. Amyloid_glyco_Cu-bd. 1 hit.
G3DSA:3.90.570.10. Amyloid_glyco_heparin-bd. 1 hit.
G3DSA:4.10.410.10. Prot_inh_Kunz-m. 1 hit.

Pfam

PF02177. A4_EXTRA. 1 hit.
PF10515. APP_amyloid. 1 hit.
PF03494. Beta-APP. 1 hit.
PF00014. Kunitz_BPTI. 1 hit.
[Graphical view]

PRINTS

PR00203. AMYLOIDA4.
PR00204. BETAAMYLOID.

ProDom

PD000222. Prot_Inh_Kunz-m. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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 Resources

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:	June 16, 2009
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)