CPLM-002216

Genbank Nucleotide ID

Amyloid beta A4 protein

Protein Synonyms/Alias

ABPP; APPI; APP; Alzheimer disease amyloid protein; Cerebral vascular amyloid peptide; CVAP; PreA4; Protease nexin-II; PN-II; N-APP; Soluble APP-alpha; S-APP-alpha; Soluble APP-beta; S-APP-beta; 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; Amyloid intracellular domain 59; AICD-59; AID(59); Gamma-CTF(59); Gamma-secretase C-terminal fragment 57; Amyloid intracellular domain 57; AICD-57; AID(57); Gamma-CTF(57); Gamma-secretase C-terminal fragment 50; Amyloid intracellular domain 50; AICD-50; AID(50); Gamma-CTF(50); C31

Homo sapiens (Human)

Position	Peptide	Type	References
662	GSGLTNIKTEEISEV	sumoylation	[1]
670	TEEISEVKMDAEFRH	sumoylation	[1]
751	PEERHLSKMQQNGYE	ubiquitination	[2, 3, 4, 5, 6]
763	GYENPTYKFFEQMQN	ubiquitination	[2, 3, 5, 6]

[1] SUMO and its role in human diseases.
Sarge KD, Park-Sarge OK.
Int Rev Cell Mol Biol. 2011;288:167-83. [PMID: 21482412]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

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 inhibits 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. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. 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. 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.

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.
MOTIF 724 734 Basolateral sorting signal.
MOTIF 759 762 NPXY motif; contains endocytosis signal.
METAL 147 147 Copper 1.
METAL 151 151 Copper 1.
METAL 168 168 Copper 1.
METAL 677 677 Copper or zinc 2.
METAL 681 681 Copper or zinc 2 (Probable).
METAL 684 684 Copper or zinc 2.
METAL 685 685 Copper or zinc 2.
MOD_RES 198 198 Phosphoserine; by CK2.
MOD_RES 206 206 Phosphoserine; by CK1.
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; alternate.
MOD_RES 757 757 Phosphotyrosine; by ABL1; alternate (By
CARBOHYD 542 542 N-linked (GlcNAc...).
CARBOHYD 571 571 N-linked (GlcNAc...) (Probable).
CARBOHYD 614 614 O-linked (GalNAc...).
CARBOHYD 623 623 O-linked (GalNAc...).
CARBOHYD 628 628 O-linked (GalNAc...).
CARBOHYD 633 633 O-linked (GalNAc...).
CARBOHYD 651 651 O-linked (GalNAc...).
CARBOHYD 652 652 O-linked (GalNAc...).
CARBOHYD 656 656 O-linked (Xyl...) (chondroitin sulfate);
CARBOHYD 659 659 O-linked (GalNAc...).
CARBOHYD 663 663 O-linked (GalNAc...) (Probable).
CARBOHYD 667 667 O-linked (GalNAc...) (Probable).
CARBOHYD 679 679 O-linked (GalNAc...).
CARBOHYD 697 697 O-linked (GalNAc...).
DISULFID 38 62
DISULFID 73 117
DISULFID 98 105
DISULFID 133 187
DISULFID 144 174
DISULFID 158 186
DISULFID 291 341
DISULFID 300 324
DISULFID 316 337

3D-structure; Alternative splicing; Alzheimer disease; Amyloid; Amyloidosis; Apoptosis; Cell adhesion; Coated pit; Complete proteome; Copper; Direct protein sequencing; Disease mutation; Disulfide bond; Endocytosis; Glycoprotein; Heparin-binding; Iron; Membrane; Metal-binding; Neurodegeneration; Notch signaling pathway; Phosphoprotein; Polymorphism; Protease inhibitor; Proteoglycan; Reference proteome; Serine protease inhibitor; Signal; Transmembrane; Transmembrane helix; Zinc.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0045177; C:apical part of cell; IEA:Compara.
GO:0030424; C:axon; ISS:UniProtKB.
GO:0009986; C:cell surface; IDA:UniProtKB.
GO:0035253; C:ciliary rootlet; IEA:Compara.
GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0043198; C:dendritic shaft; IDA:MGI.
GO:0043197; C:dendritic spine; IDA:MGI.
GO:0005576; C:extracellular region; TAS:Reactome.
GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
GO:0031594; C:neuromuscular junction; IEA:Compara.
GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
GO:0051233; C:spindle midzone; IEA:Compara.
GO:0045202; C:synapse; IDA:MGI.
GO:0003677; F:DNA binding; ISS:UniProtKB.
GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
GO:0016504; F:peptidase activator activity; IEA:Compara.
GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
GO:0046914; F:transition metal ion binding; IEA:InterPro.
GO:0008344; P:adult locomotory behavior; ISS:UniProtKB.
GO:0008088; P:axon cargo transport; ISS:UniProtKB.
GO:0016199; P:axon midline choice point recognition; ISS:UniProtKB.
GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
GO:0006878; P:cellular copper ion homeostasis; ISS:UniProtKB.
GO:0008203; P:cholesterol metabolic process; IEA:Compara.
GO:0048669; P:collateral sprouting in absence of injury; ISS:UniProtKB.
GO:0016358; P:dendrite development; ISS:UniProtKB.
GO:0006897; P:endocytosis; ISS:UniProtKB.
GO:0030198; P:extracellular matrix organization; ISS:UniProtKB.
GO:0030900; P:forebrain development; IEA:Compara.
GO:0000085; P:G2 phase of mitotic cell cycle; ISS:UniProtKB.
GO:0006917; P:induction of apoptosis; IEA:Compara.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
GO:0007617; P:mating behavior; ISS:UniProtKB.
GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
GO:0045665; P:negative regulation of neuron differentiation; IEA:Compara.
GO:0050885; P:neuromuscular process controlling balance; IEA:Compara.
GO:0051402; P:neuron apoptotic process; IMP:UniProtKB.
GO:0016322; P:neuron remodeling; ISS:UniProtKB.
GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
GO:0030168; P:platelet activation; TAS:Reactome.
GO:0002576; P:platelet degranulation; TAS:Reactome.
GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
GO:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB.
GO:0043393; P:regulation of protein binding; IEA:Compara.
GO:0050803; P:regulation of synapse structure and activity; ISS:UniProtKB.
GO:0006417; P:regulation of translation; ISS:UniProtKB.
GO:0006979; P:response to oxidative stress; IEA:Compara.
GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IEA:Compara.
GO:0001967; P:suckling behavior; IEA:Compara.
GO:0051124; P:synaptic growth at neuromuscular junction; IEA:Compara.
GO:0008542; P:visual learning; ISS:UniProtKB.

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.

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

SM00006; A4_EXTRA
SM00131; KU

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

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