UniProt Accession

 A4_MOUSE; P12023; P97487; P97942; Q99K32 

Genbank Protein ID

 M18373; X59379; U84012; D10603; BC005490; M24397; X15210; U82624 

Genbank Nucleotide ID

 AAA37139.1; AAB41502.1; BAA01456.1; AAH05490.1; AAA39929.1; CAA33280.1; AAB40919.1 

Protein Name

 Amyloid beta A4 protein 

Protein Synonyms/Alias

 ABPP; APP; Alzheimer disease amyloid A4 protein homolog; Amyloidogenic glycoprotein; AG; N-APP; Soluble APP-alpha; S-APP-alpha; Soluble APP-beta; S-APP-beta; C99; APP-C99; Beta-amyloid protein 42; Beta-APP42; Beta-amyloid protein 40; Beta-APP40; C83; P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59; APP-C59; Amyloid intracellular domain 59; AID(59); Gamma-CTF(59); Gamma-secretase C-terminal fragment 57; APP-C57; Amyloid intracellular domain 57; AID(57); Gamma-CTF(57); Gamma-secretase C-terminal fragment 50; Amyloid intracellular domain 50; AID(50); Gamma-CTF(50); C31 

Gene Name

 App 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
726	TLVMLKKKQYTSIHH	ubiquitination	[1]
751	PEERHLSKMQQNGYE	ubiquitination	[1]
763	GYENPTYKFFEQMQN	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 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 Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. 

Sequence Annotation

 DOMAIN 291 341 BPTI/Kunitz inhibitor.
 REGION 96 110 Heparin-binding (By similarity).
 REGION 181 188 Zinc-binding (By similarity).
 REGION 391 423 Heparin-binding (By similarity).
 REGION 491 522 Heparin-binding (By similarity).
 REGION 523 540 Collagen-binding (By similarity).
 REGION 732 751 Interaction with G(o)-alpha (By
 REGION 756 770 Interaction with DAB2.
 MOTIF 724 734 Basolateral sorting signal.
 MOTIF 759 762 NPXY motif; contains endocytosis signal.
 METAL 147 147 Copper 1 (By similarity).
 METAL 151 151 Copper 1 (By similarity).
 METAL 168 168 Copper 1 (By similarity).
 METAL 677 677 Copper or zinc 2 (By similarity).
 METAL 685 685 Copper or zinc 2 (By similarity).
 MOD_RES 198 198 Phosphoserine; by CK2 (By similarity).
 MOD_RES 206 206 Phosphoserine; by CK1 (By similarity).
 MOD_RES 729 729 Phosphothreonine (By similarity).
 MOD_RES 730 730 Phosphoserine; by APP-kinase I (By
 MOD_RES 743 743 Phosphothreonine; by CDK5 and MAPK10.
 MOD_RES 757 757 Phosphotyrosine; by ABL1.
 CARBOHYD 542 542 N-linked (GlcNAc...) (Probable).
 CARBOHYD 571 571 N-linked (GlcNAc...) (Probable).
 DISULFID 38 62 By similarity.
 DISULFID 73 117 By similarity.
 DISULFID 98 105 By similarity.
 DISULFID 133 187 By similarity.
 DISULFID 144 174 By similarity.
 DISULFID 158 186 By similarity.
 DISULFID 291 341 By similarity.
 DISULFID 300 324 By similarity.
 DISULFID 316 337 By similarity.  

Keyword

 3D-structure; Alternative splicing; Amyloid; Apoptosis; Cell adhesion; Coated pit; Complete proteome; Copper; Disulfide bond; Endocytosis; Glycoprotein; Heparin-binding; Iron; Membrane; Metal-binding; Notch signaling pathway; Phosphoprotein; Protease inhibitor; Reference proteome; Serine protease inhibitor; Signal; Transmembrane; Transmembrane helix; Zinc. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 770 AA 

Protein Sequence

Gene Ontology

 GO:0045177; C:apical part of cell; IDA:MGI.
 GO:0030424; C:axon; IDA:MGI.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0035253; C:ciliary rootlet; IDA:MGI.
 GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
 GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
 GO:0043198; C:dendritic shaft; IEA:Compara.
 GO:0043197; C:dendritic spine; IEA:Compara.
 GO:0005794; C:Golgi apparatus; IDA:MGI.
 GO:0016021; C:integral to membrane; IDA:MGI.
 GO:0031594; C:neuromuscular junction; IDA:MGI.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
 GO:0005886; C:plasma membrane; IDA:MGI.
 GO:0051233; C:spindle midzone; IDA:MGI.
 GO:0003677; F:DNA binding; IDA:MGI.
 GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
 GO:0016504; F:peptidase activator activity; IEA:Compara.
 GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
 GO:0046914; F:transition metal ion binding; IEA:InterPro.
 GO:0008344; P:adult locomotory behavior; IMP:MGI.
 GO:0008088; P:axon cargo transport; IMP:MGI.
 GO:0016199; P:axon midline choice point recognition; IMP:MGI.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0006878; P:cellular copper ion homeostasis; IMP:MGI.
 GO:0008203; P:cholesterol metabolic process; IMP:MGI.
 GO:0048669; P:collateral sprouting in absence of injury; IGI:MGI.
 GO:0016358; P:dendrite development; IMP:MGI.
 GO:0006897; P:endocytosis; IMP:MGI.
 GO:0030198; P:extracellular matrix organization; IGI:MGI.
 GO:0030900; P:forebrain development; IMP:MGI.
 GO:0006917; P:induction of apoptosis; IEA:Compara.
 GO:0035235; P:ionotropic glutamate receptor signaling pathway; IMP:MGI.
 GO:0007617; P:mating behavior; IGI:MGI.
 GO:0006378; P:mRNA polyadenylation; IDA:MGI.
 GO:0045665; P:negative regulation of neuron differentiation; IDA:MGI.
 GO:0050885; P:neuromuscular process controlling balance; IGI:MGI.
 GO:0051402; P:neuron apoptotic process; IGI:MGI.
 GO:0016322; P:neuron remodeling; IMP:MGI.
 GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
 GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:MGI.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI.
 GO:0006468; P:protein phosphorylation; IMP:MGI.
 GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; IGI:MGI.
 GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
 GO:0043393; P:regulation of protein binding; IMP:MGI.
 GO:0050803; P:regulation of synapse structure and activity; IMP:MGI.
 GO:0006417; P:regulation of translation; IDA:MGI.
 GO:0006979; P:response to oxidative stress; IGI:MGI.
 GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IGI:MGI.
 GO:0001967; P:suckling behavior; IGI:MGI.
 GO:0051124; P:synaptic growth at neuromuscular junction; IGI:MGI.
 GO:0008542; P:visual learning; IMP:MGI. 

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. 

Pfam

 PF10515; APP_amyloid
 PF12924; APP_Cu_bd
 PF12925; APP_E2
 PF02177; APP_N
 PF03494; Beta-APP
 PF00014; Kunitz_BPTI 

SMART

 SM00006; A4_EXTRA
 SM00131; KU 

PROSITE

 PS00319; A4_EXTRA
 PS00320; A4_INTRA
 PS00280; BPTI_KUNITZ_1
 PS50279; BPTI_KUNITZ_2 

PRINTS

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