LipidDB ID

LipidDB-10090-00952

Entry Name

UniProt Accession

P12023; P97487; P97942; Q99K32;

Theoretical PI

4.71

Molecular Weight

86722.05

Genbank Protein ID

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

Genbank Nucleotide ID

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

Protein Name

C31

Protein Synonyms/Alias

ABPP; APP; Alzheimer disease amyloid A4 protein homolog; Amyloidogenic glycoprotein; AG; S-APP-alpha; S-APP-beta; APP-C99; Beta-APP42; Beta-APP40; APP-C59; Amyloid intracellular domain 59; AID(59); Gamma-CTF(59); APP-C57; Amyloid intracellular domain 57; AID(57); Gamma-CTF(57); Amyloid intracellular domain 50; AID(50); Gamma-CTF(50);

Gene Name

App

Gene Synonyms/Alias

Created Date

01-OCT-1989

Organism

Mus musculus (Mouse)

NCBI Taxa ID

10090

Reference

[1] Bhattacharyya R, Barren C, Kovacs DM. Palmitoylation of amyloid precursorprotein regulates amyloidogenic processing in lipid rafts. J Neurosci. 2013 Jul3;33(27):11169-83. doi: 10.1523/JNEUROSCI.4704-12.2013.[PMID:23825420]

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

Topological domain: 18 699 Extracellular.
Transmembrane: 700 723 Helical.
Topological domain: 724 770 Cytoplasmic.
Domain: 291 341 BPTI/Kunitz inhibitor.
Region: 96 110 Heparin-binding.
Region: 181 188 Zinc-binding.
Region: 391 423 Heparin-binding.
Region: 491 522 Heparin-binding.
Region: 523 540 Collagen-binding.
Region: 732 751 Interaction with G(o)-alpha.
Region: 756 770 Interaction with DAB2.
Motif: 724 734 Basolateral sorting signal.
Motif: 759 762 NPXY motif; contains endocytosis signal.
Metal binding site: 147 147 Copper 1.
Metal binding site: 151 151 Copper 1.
Metal binding site: 168 168 Copper 1.
Metal binding site: 677 677 Copper or zinc 2.
Metal binding site: 685 685 Copper or zinc 2.
Functional site: 144 144 Required for Cu(2+) reduction.
Functional site: 301 302 Reactive bond.
Functional site: 671 672 Cleavage; by beta-secretase.
Functional site: 672 673 Cleavage; by caspase-6.
Functional site: 687 688 Cleavage; by alpha-secretase.
Functional site: 690 691 Cleavage; by theta-secretase.
Functional site: 704 704 Implicated in free radical propagation.
Functional site: 711 712 Cleavage; by gamma-secretase; site 1.
Functional site: 713 714 Cleavage; by gamma-secretase; site 2.
Functional site: 720 721 Cleavage; by gamma-secretase; site 3.
Functional site: 739 740 Cleavage; by caspase-6, caspase-8 orcaspase-9.
Modified residue: 198 198 Phosphoserine; by CK2.
Modified residue: 206 206 Phosphoserine; by CK1.
Modified residue: 729 729 Phosphothreonine.
Modified residue: 730 730 Phosphoserine; by APP-kinase I.
Modified residue: 743 743 Phosphothreonine; by CDK5 and MAPK10.
Modified residue: 757 757 Phosphotyrosine; by ABL1.

Protein Length

770 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0045177; C:apical part of cell; IDA:MGI
GO:0030424; C:axon; IDA:MGI
GO:0009986; C:cell surface; IEA:Ensembl
GO:0005911; C:cell-cell junction; IDA:MGI
GO:0035253; C:ciliary rootlet; IDA:MGI
GO:0005905; C:coated pit; IEA:UniProtKB-KW
GO:0005737; C:cytoplasm; IDA:MGI
GO:0031410; C:cytoplasmic vesicle; IDA:MGI
GO:0043198; C:dendritic shaft; IEA:Ensembl
GO:0043197; C:dendritic spine; IEA:Ensembl
GO:0030134; C:ER to Golgi transport vesicle; IDA:MGI
GO:0005615; C:extracellular space; IEA:Ensembl
GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl
GO:0005794; C:Golgi apparatus; IDA:MGI
GO:0016021; C:integral component of membrane; IDA:MGI
GO:0016020; C:membrane; IDA:MGI
GO:0045121; C:membrane raft; IEA:Ensembl
GO:0031594; C:neuromuscular junction; IDA:MGI
GO:0043005; C:neuron projection; IDA:MGI
GO:0005641; C:nuclear envelope lumen; IEA:Ensembl
GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI
GO:0005886; C:plasma membrane; IDA:MGI
GO:0043235; C:receptor complex; ISO: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:Ensembl
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:0007409; P:axonogenesis; 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:0035235; P:ionotropic glutamate receptor signaling pathway; IMP:MGI
GO:0007626; P:locomotory behavior; IGI: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:0031175; P:neuron projection development; IDA: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:0045931; P:positive regulation of mitotic cell cycle; IMP:MGI
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI
GO:0051260; P:protein homooligomerization; ISO:MGI
GO:0006468; P:protein phosphorylation; IMP:MGI
GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; IGI:MGI
GO:0010468; P:regulation of gene expression; IDA: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

InterPro; IPR008155; Amyloid_glyco
InterPro; IPR013803; Amyloid_glyco_Abeta
InterPro; IPR011178; Amyloid_glyco_Cu-bd
InterPro; IPR024329; Amyloid_glyco_E2_domain
InterPro; IPR008154; Amyloid_glyco_extra
InterPro; IPR019744; Amyloid_glyco_extracell_CS
InterPro; IPR015849; Amyloid_glyco_heparin-bd
InterPro; IPR019745; Amyloid_glyco_intracell_CS
InterPro; IPR028866; APP
InterPro; IPR019543; APP_amyloid_C
InterPro; IPR002223; Prot_inh_Kunz-m
InterPro; IPR020901; Prtase_inh_Kunz-CS

Pfam

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

SMART

SMART; SM00006; A4_EXTRA;
SMART; SM00131; KU;

PROSITE

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

PRINTS

PRINTS; PR00203; AMYLOIDA4;
PRINTS; PR00759; BASICPTASE;
PRINTS; PR00204; BETAAMYLOID;