DegronMD - P05067(APP)

FUNCTION: Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). 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 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (PubMed:17062754, PubMed:23011729). 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. {ECO:0000250, ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:17062754, ECO:0000269|PubMed:23011729, ECO:0000269|PubMed:25122912}.; FUNCTION: Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.; FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. {ECO:0000250}.; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.; FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). View more >>

GO - Biological processes (BP): adenylate cyclase-activating G protein-coupled receptor signaling pathway [GO:0007189]; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway [GO:0007193]; adult locomotory behavior [GO:0008344]; amyloid fibril formation [GO:1990000]; antibacterial humoral response [GO:0019731]; antifungal humoral response [GO:0019732]; antimicrobial humoral immune response mediated by antimicrobial peptide [GO:0061844]; associative learning [GO:0008306]; astrocyte activation [GO:0048143]; astrocyte activation involved in immune response [GO:0002265]; axo-dendritic transport [GO:0008088]; axon midline choice point recognition [GO:0016199]; axonogenesis [GO:0007409]; calcium-mediated signaling [GO:0019722]; cell adhesion [GO:0007155]; cellular copper ion homeostasis [GO:0006878]; cellular response to amyloid-beta [GO:1904646]; cellular response to cAMP [GO:0071320]; cellular response to copper ion [GO:0071280]; cellular response to manganese ion [GO:0071287]; cellular response to nerve growth factor stimulus [GO:1990090]; cellular response to norepinephrine stimulus [GO:0071874]; central nervous system development [GO:0007417]; cholesterol metabolic process [GO:0008203]; cognition [GO:0050890]; collateral sprouting in absence of injury [GO:0048669]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; dendrite development [GO:0016358]; endocytosis [GO:0006897]; extracellular matrix organization [GO:0030198]; forebrain development [GO:0030900]; G protein-coupled receptor signaling pathway [GO:0007186]; innate immune response [GO:0045087]; ionotropic glutamate receptor signaling pathway [GO:0035235]; learning [GO:0007612]; learning or memory [GO:0007611]; lipoprotein metabolic process [GO:0042157]; locomotory behavior [GO:0007626]; mating behavior [GO:0007617]; memory [GO:0007613]; microglia development [GO:0014005]; microglial cell activation [GO:0001774]; modulation of age-related behavioral decline [GO:0090647]; modulation of excitatory postsynaptic potential [GO:0098815]; mRNA polyadenylation [GO:0006378]; negative regulation of blood circulation [GO:1903523]; negative regulation of canonical Wnt signaling pathway [GO:0090090]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of dendritic spine maintenance [GO:1902951]; negative regulation of gene expression [GO:0010629]; negative regulation of long-term synaptic potentiation [GO:1900272]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of mitochondrion organization [GO:0010823]; negative regulation of neuron death [GO:1901215]; negative regulation of neuron differentiation [GO:0045665]; negative regulation of protein localization to nucleus [GO:1900181]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of Wnt signaling pathway [GO:0030178]; neuromuscular process controlling balance [GO:0050885]; neuron apoptotic process [GO:0051402]; neuron projection development [GO:0031175]; neuron projection maintenance [GO:1990535]; neuron remodeling [GO:0016322]; Notch signaling pathway [GO:0007219]; positive regulation of 1-phosphatidylinositol-3-kinase activity [GO:0061903]; positive regulation of amyloid fibril formation [GO:1905908]; positive regulation of apoptotic process [GO:0043065]; positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process [GO:1902961]; positive regulation of cell activation [GO:0050867]; positive regulation of cellular response to thapsigargin [GO:1905893]; positive regulation of cellular response to tunicamycin [GO:1905896]; positive regulation of chemokine production [GO:0032722]; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of endothelin production [GO:1904472]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of excitatory postsynaptic potential [GO:2000463]; positive regulation of G2/M transition of mitotic cell cycle [GO:0010971]; positive regulation of gene expression [GO:0010628]; positive regulation of glycolytic process [GO:0045821]; positive regulation of G protein-coupled receptor internalization [GO:1904022]; positive regulation of G protein-coupled receptor signaling pathway [GO:0045745]; positive regulation of histone acetylation [GO:0035066]; positive regulation of inflammatory response [GO:0050729]; positive regulation of interferon-gamma production [GO:0032729]; positive regulation of interleukin-1 beta production [GO:0032731]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of JNK cascade [GO:0046330]; positive regulation of long-term synaptic depression [GO:1900454]; positive regulation of long-term synaptic potentiation [GO:1900273]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of membrane protein ectodomain proteolysis [GO:0051044]; positive regulation of mitotic cell cycle [GO:0045931]; positive regulation of monocyte chemotaxis [GO:0090026]; positive regulation of neuron apoptotic process [GO:0043525]; positive regulation of neuron death [GO:1901216]; positive regulation of neuron differentiation [GO:0045666]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of NIK/NF-kappaB signaling [GO:1901224]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of oxidative stress-induced neuron death [GO:1903223]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of peptidyl-threonine phosphorylation [GO:0010800]; positive regulation of phosphorylation [GO:0042327]; positive regulation of protein binding [GO:0032092]; positive regulation of protein import [GO:1904591]; positive regulation of protein kinase A signaling [GO:0010739]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein metabolic process [GO:0051247]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein tyrosine kinase activity [GO:0061098]; positive regulation of receptor binding [GO:1900122]; positive regulation of response to endoplasmic reticulum stress [GO:1905898]; positive regulation of superoxide anion generation [GO:0032930]; positive regulation of tau-protein kinase activity [GO:1902949]; positive regulation of T cell migration [GO:2000406]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of tumor necrosis factor production [GO:0032760]; protein homooligomerization [GO:0051260]; protein phosphorylation [GO:0006468]; protein tetramerization [GO:0051262]; protein trimerization [GO:0070206]; regulation of acetylcholine-gated cation channel activity [GO:1903048]; regulation of amyloid-beta clearance [GO:1900221]; regulation of amyloid fibril formation [GO:1905906]; regulation of dendritic spine maintenance [GO:1902950]; regulation of epidermal growth factor-activated receptor activity [GO:0007176]; regulation of gene expression [GO:0010468]; regulation of long-term neuronal synaptic plasticity [GO:0048169]; regulation of MAPK cascade [GO:0043408]; regulation of multicellular organism growth [GO:0040014]; regulation of NMDA receptor activity [GO:2000310]; regulation of peptidyl-tyrosine phosphorylation [GO:0050730]; regulation of presynapse assembly [GO:1905606]; regulation of protein tyrosine kinase activity [GO:0061097]; regulation of response to calcium ion [GO:1905945]; regulation of signaling receptor activity [GO:0010469]; regulation of spontaneous synaptic transmission [GO:0150003]; regulation of synapse structure or activity [GO:0050803]; regulation of toll-like receptor signaling pathway [GO:0034121]; regulation of transcription by RNA polymerase II [GO:0006357]; regulation of translation [GO:0006417]; regulation of Wnt signaling pathway [GO:0030111]; response to interleukin-1 [GO:0070555]; response to lead ion [GO:0010288]; response to oxidative stress [GO:0006979]; response to yeast [GO:0001878]; smooth endoplasmic reticulum calcium ion homeostasis [GO:0051563]; suckling behavior [GO:0001967]; synapse organization [GO:0050808]; synaptic assembly at neuromuscular junction [GO:0051124]; visual learning [GO:0008542] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Open in full screen with detailed sequence annotations

Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K393E	TCGA-05-4398	LUAD	TCGA	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation blocking ubiquitination signal	0.5556
p.E285Q	TCGA-AC-A23H	BRCA	TCGA	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.1111
p.E380K	TCGA-CN-A6V7	HNSC	TCGA	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.591
p.E380K	SIDM01716	Non-Cancerous	GDSC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.591
p.E380K	SIDM00175	Melanoma	GDSC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.591
p.E380K	ACH-002096	Skin Cancer	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.591
p.E380K	ACH-002346	Non-Cancerous	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.591
p.A394T	TCGA-DF-A2KU	UCEC	TCGA	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0833
p.E284K	TCGA-EE-A29D	SKCM	TCGA	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.1389
p.G383W	TCGA-EE-A2MM	SKCM	TCGA	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.6714
p.T274A	TCGA-EY-A2OM	UCEC	TCGA	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.6028
p.T274A	ACH-000963	Colon/Colorectal Cancer	CCLE	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.6028
p.A273T	TCGA-IB-7651	PAAD	TCGA	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.7139
p.E263K	TCGA-SJ-A6ZI	UCEC	TCGA	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.0556
p.E263K	ACH-001356	Thyroid Cancer	CCLE	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.0556
p.F391V	TCGA-Z2-A8RT	SKCM	TCGA	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.1667
p.E385Q	DO225168	BRCA	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.6744
p.R287C	DO8264	COAD	ICGC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.0556
p.E382K	DO230311	COCA	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.7022
p.E382K	DO23258	LINC	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.7022
p.Q394R	DO230335	COCA	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0833
p.D373E	DO229031	LICA	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.1667
p.K374E	DO25847	LUAD	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.1944
p.A393S	DO26150	LUAD	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation blocking ubiquitination signal	0.5556
p.N276S	DO46330	OV	ICGC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.7069
p.R385C	DO232675	PBCA	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.8301
p.R385C	DO41871	UCEC	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.8301
p.R385C	SK-UT-1	soft tissue	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.8301
p.F372V	DO51301	SKCM	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.1389
p.A284T	DO223286	UCEC	ICGC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.1389
p.F381L	DO41133	UCEC	ICGC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.6981
p.K395N	SIDM01103	Squamous Cell Lung Carcinoma	GDSC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation substituting flanking lysine	0.1667
p.K395N	ACH-000665	Lung Cancer	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation substituting flanking lysine	0.1667
p.K395N	SK-MES-1	lung	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation substituting flanking lysine	0.1667
p.A369V	SIDM00789	Colorectal Carcinoma	GDSC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0556
p.A369V	ACH-000997	Colon/Colorectal Cancer	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0556
p.A369V	ACH-001061	Colon/Colorectal Cancer	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0556
p.A369V	HCT-15	large intestine	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0556
p.H388Y	SIDM00451	T-Lymphoblastic Leukemia	GDSC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.25
p.H388Y	ACH-000937	Leukemia	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.25
p.H388Y	PF-382	haematopoietic and lymphoid tissue	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.25
p.E385K	ACH-001415	Bladder Cancer	CCLE	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.7022
p.M382V	EN	endometrium	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.7208
p.A393T	CTV-1	haematopoietic and lymphoid tissue	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation blocking ubiquitination signal	0.5556
p.K379N	TE-9	oesophagus	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.6918
p.K379N	JHH-4	liver	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.6918
p.K379N	KYM-1	soft tissue	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.6918
p.M275V	EN	endometrium	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.7208
p.Q384H	CW-2	large intestine	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.7582
p.K285N	SK-MES-1	lung	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.1111
p.R395C	SNU-1040	large intestine	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation substituting flanking lysine	0.1667
p.Q389H	CW-2	large intestine	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.2222
p.E393K	EPLC-272H	lung	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation blocking ubiquitination signal	0.5556
p.E286K	EPLC-272H	lung	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.0833
p.H380Y	HSC-39	stomach	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation altering degron motif	0.7229
p.M387V	EN	endometrium	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.2778
p.R283Q	COR-L105	lung	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.1667
p.H369Y	PF-382	haematopoietic and lymphoid tissue	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0556
p.A369S	CAL-12T	lung	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.0556
p.Q277H	CW-2	large intestine	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.7582
p.H278Y	PF-382	haematopoietic and lymphoid tissue	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.3056
p.K371N	SK-MES-1	lung	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.1111
p.D371H	NCI-H510A	lung	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.1111
p.P389H	CML-T1	haematopoietic and lymphoid tissue	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.2222
p.K376N	SK-MES-1	lung	COSMIC	LETPGDE	DEG_SCF_FBW7_2	379:385	Mutation rewiring degron network	0.25
p.K264N	SK-MES-1	lung	COSMIC	ATTTT	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.0833

DegronMD: protein-targeted degradation, mutation and drug response to degrons

APP

UniProt ID: P05067

Entrez ID: 351

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for APP in