UniProt Summary Literature Review Cleavage Sites Topological Domains Proteolytic Cleavage Secretome Detection
UniProt Summary
UniProt ID

P05067
Entry Name

A4_HUMAN
Protein Name

Amyloid-beta precursor protein
Primary Gene Name

APP
Organism

Homo sapiens (Human)
Molecular Function

Serine protease inhibitor
Protease inhibitor
Heparin-binding
Membrane Location

Secreted
Cell membrane
Membrane



Biological Literature Report of Shedding
Substrate Name Amyloid beta A4 protein precursor (APP)
Cell Type neurons; central nervous system (CNS)
Substrate Description anti-amyloidogenic, neuroprotective (α-secretase) , amyloidogenic pathway (β-secretase)
Substrate Function Category central nervous system (neuron)
Substrate Function Subtype Central nervous system (CNS) pathology
Sheddase α-secretase(ADAM10, ADAM17), β-Secretase(BACE)
Shedding-related Disease cell receptor
Short Summary of Papers the shedding of APP by ADAM (α-secretase) suppress β-amyloid formation (anti-amyloidogenic, neuroprotective)
Cleavage Information NONE
PMID 22553493 18951988



Cleavage Site Diagram



Topological Domains
Topological Domains
 		Start End
Extracellular
 		18 701
Transmembrane
 		702 722



Proteolytic Cleavage
Database CutSeq Mapped Position Protease Type Evidence PMID
ASCENT TARA*LEVP 17 UNKNOWN subtiligase-based N-terminal sequencing 33536314   
PAPER TARA*LEVP 17 UNKNOWN Mass spectrometry 33796845   
PAPER SEQA*ETGP 295 UNKNOWN Mass spectrometry 33796845   
PAPER EYCM*AVCG 338 UNKNOWN Mass spectrometry 33796845   
PAPER GDEN*EHAH 386 UNKNOWN Mass spectrometry 33796845   
ASCENT ADKK*AVIQ 429 UNKNOWN subtiligase-based N-terminal sequencing 33536314   
PAPER VLAN*MISE 579 UNKNOWN Mass spectrometry 33796845   
PAPER LANM*ISEP 580 UNKNOWN Mass spectrometry 33796845   
PAPER ELLP*VNGE 608 UNKNOWN Mass spectrometry 33796845   
PAPER PVNG*EFSL 611 UNKNOWN Mass spectrometry 33796845   
HPRD EISE*VKMD 668 Cathepsin D 8943232   
HPRD EISE*VKMD 668 Cathepsin D 8943232   
HPRD EISE*VKMD 668 Cathepsin D 8943232   
HPRD VKMD*AEFR 672 Caspase 6; Beta site App cleaving enzyme; 10438520    10531052    10677483   
HPRD VKMD*AEFR 672 Caspase 6; Beta site App cleaving enzyme; 10438520    10531052   
HPRD VKMD*AEFR 672 Caspase 6; Beta site App cleaving enzyme; 10438520    10531052   
HPRD MDAE*FRHD 674 Cathepsin D 8943232   
HPRD MDAE*FRHD 674 Cathepsin D 8943232   
HPRD MDAE*FRHD 674 Cathepsin D 8943232   
PAPER HHQK*LVFF 687 UNKNOWN Mass spectrometry 33796845   
PAPER HQKL*VFFA 688 UNKNOWN Mass spectrometry 33796845   
HPRD KLVF*FAED 690 Cathepsin D; Beta site APP cleaving enzyme 2; 10605825    10931940   
HPRD KLVF*FAED 690 Cathepsin D; Beta site APP cleaving enzyme 2; 10605825    10931940   
HPRD KLVF*FAED 690 10605825    10931940   
HPRD LVFF*AEDV 691 Cathepsin D; Beta site APP cleaving enzyme 2; 10605825    10931940   
HPRD LVFF*AEDV 691 Cathepsin D; Beta site APP cleaving enzyme 2; 10605825    10931940    8943232    10605825    10931940   
HPRD LVFF*AEDV 691 Cathepsin D; Beta site APP cleaving enzyme 2; 10605825    10931940   
HPRD IIGL*MVGG 705 Cathepsin D 10605825   
HPRD IIGL*MVGG 705 Cathepsin D 10605825   
HPRD IIGL*MVGG 705 Cathepsin D 10605825   
PAPER LMVG*GVVI 708 UNKNOWN Mass spectrometry 33796845   
PAPER MVGG*VVIA 709 UNKNOWN Mass spectrometry 33796845   
PAPER GGVV*IATV 711 UNKNOWN Mass spectrometry 33796845   
HPRD VVIA*TVIV 713 Cathepsin D 10605825   
HPRD VVIA*TVIV 713 Cathepsin D 10605825   
HPRD VVIA*TVIV 713 Cathepsin D 10605825   
HPRD VIAT*VIVI 714 Cathepsin D 10605825   
HPRD VIAT*VIVI 714 Cathepsin D 10605825   
HPRD VIAT*VIVI 714 Cathepsin D 10605825   
HPRD IVIT*LVML 719 Cathepsin D 10605825   
HPRD IVIT*LVML 719 Cathepsin D 10605825   
HPRD IVIT*LVML 719 Cathepsin D 10605825   
HPRD VITL*VMLK 720 Cathepsin D 10605825    8943232   
HPRD VITL*VMLK 720 Cathepsin D 10605825    8943232   
HPRD VITL*VMLK 720 Cathepsin D 10605825    8943232   
HPRD VEVD*AAVT 739 Cathepsin D; Caspase 3, apoptosis-related cysteine peptidase; 8943232   
HPRD VEVD*AAVT 739 Cathepsin D 8943232   
HPRD VEVD*AAVT 739 Cathepsin D; Caspase 3, apoptosis-related cysteine peptidase; 8943232   
HPRD TYKF*FEQM 764 Cathepsin D 10605825    8943232   
HPRD TYKF*FEQM 764 Cathepsin D 10605825    8943232   
HPRD TYKF*FEQM 764 Cathepsin D 10605825    8943232   
PAPER No_information ADAM9, ADAM10, ADAM17 12535668   



Secretome Detection
Secretome Database Cell Type or Body Fluid PubMed Reference
PAPER platelet 20962327
PAPER cancer(ovary) 18560578
SPD 22728825
Sys-BodyFluid Milk 16502470
Sys-BodyFluid Seminal Fluid 16709260
Sys-BodyFluid Saliva 17614365
Sys-BodyFluid Saliva 18361515
Sys-BodyFluid Cerebrospinal fluid 17853512
Sys-BodyFluid Cerebrospinal fluid 18052119
Sys-BodyFluid Cerebrospinal fluid 17022648
Sys-BodyFluid Cerebrospinal fluid 15582749
Sys-BodyFluid Urine 16335936
Sys-BodyFluid Urine 16948836
Sys-BodyFluid Plasma/Serum 14718574
Sys-BodyFluid Cerebrospinal fluid 14998169
Sys-BodyFluid Amniotic fluid 17495049
HCSD cancer (gastric cancer) 23161554
HCSD cancer(lung cancer) 19776420
HCSD cancer(prostate cancer) 22908226
HCSD cancer(23 cancer cell lines) 20124221
HCSD cancer(pancreatic cancer) 16215274
HCSD cancer(colon tumor) 23684732
HCSD cancer(colorectal cancer 22408128
HCSD cancer(colorectal cancer 24418523
HCSD cancer(colorectal cancer) 24681409
HCSD cancer(colorectal carsinoma) 23585443
HCSD cancer(colorectal cancer) 25216327
HCSD cancer(head and neck squamous cell carcinoma) 22918226
HCSD cancer(urothelial carcinoma) 23591195
HCSD cancer(glioblastoma multiforme) 21574646
HCSD cancer(lung adenocarcinoma) 22896658
HCSD cancer(breast cancer) 24505115
HCSD cancer(pancreatic cancer) 21625447
HCSD cancer(ovarian cancer) 23805888
HCSD cancer(ovarian cancer) 22623176
HCSD cancer(oral cancer ) 21714544
HCSD cancer(Lung adenocarcinoma) 22985211
HCSD cancer(Liver metastasis in colorectal cancer) 23443137
HCSD non-small cell lung cancer 21262398
HCSD cancer(Glioblastoma) 23483059
HCSD cancer(non small cell lung cancer) 19655816
locate 17986452