APP
entrez
351
canonical
uniprot
P05067
canonical
ensembl
ENSG00000142192
resolver
ensp
ENSP00000284981
resolver
ensp
ENSP00000345463
resolver
ensp
ENSP00000346129
resolver
ensp
ENSP00000350578
resolver
ensp
ENSP00000351796
resolver
ensp
ENSP00000352760
resolver
ensp
ENSP00000387483
resolver
ensp
ENSP00000398879
resolver
ensp
ENSP00000542583
resolver
ensp
ENSP00000542584
resolver
enst
ENST00000359726
resolver
enst
ENST00000439274
resolver
genesymbol
APP
resolver
genesymbol_syn
A4
resolver
genesymbol_syn
AD1
resolver
hgnc
HGNC:620
resolver
uniprot
A0A0A0MRG2
resolver
uniprot
A0A140VJC8
resolver
uniprot
B2R5V1
resolver
uniprot
B4DGD0
resolver
uniprot
B4DII8
resolver
uniprot
B4DJT9
resolver
uniprot
D3DSD1
resolver
uniprot
D3DSD2
resolver
uniprot
D3DSD3
resolver
uniprot
E9PG40
resolver
uniprot
P09000
resolver
uniprot
P78438
resolver
uniprot
Q13764
resolver
uniprot
Q13778
resolver
uniprot
Q13793
resolver
uniprot
Q16011
resolver
uniprot
Q16014
resolver
uniprot
Q16019
resolver
uniprot
Q16020
resolver
uniprot
Q6GSC0
resolver
uniprot
Q8WZ99
resolver
uniprot
Q9BT38
resolver
uniprot
Q9UC33
resolver
uniprot
Q9UCA9
resolver
uniprot
Q9UCB6
resolver
uniprot
Q9UCC8
resolver
uniprot
Q9UCD1
resolver
uniprot
Q9UQ58
resolver
uniprot_entry
A0A0A0MRG2_HUMAN
resolver
uniprot_entry
A0A140VJC8_HUMAN
resolver
uniprot_entry
A4_HUMAN
resolver
uniprot_entry
B4DGD0_HUMAN
resolver
uniprot_entry
B4DJT9_HUMAN
resolver
uniprot_entry
E9PG40_HUMAN
resolver
uniprot_sec
B2R5V1
resolver
uniprot_sec
B4DII8
resolver
uniprot_sec
D3DSD1
resolver
uniprot_sec
D3DSD2
resolver
uniprot_sec
D3DSD3
resolver
uniprot_sec
P09000
resolver
uniprot_sec
P78438
resolver
uniprot_sec
Q13764
resolver
uniprot_sec
Q13778
resolver
uniprot_sec
Q13793
resolver
uniprot_sec
Q16011
resolver
uniprot_sec
Q16014
resolver
uniprot_sec
Q16019
resolver
uniprot_sec
Q16020
resolver
uniprot_sec
Q6GSC0
resolver
uniprot_sec
Q8WZ99
resolver
uniprot_sec
Q9BT38
resolver
uniprot_sec
Q9UC33
resolver
uniprot_sec
Q9UCA9
resolver
uniprot_sec
Q9UCB6
resolver
uniprot_sec
Q9UCC8
resolver
uniprot_sec
Q9UCD1
resolver
uniprot_sec
Q9UQ58
resolver
amino_acid_sequence
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
uniprot
proteins
disease_involvement
DISEASE: Alzheimer disease 1 (AD1) [MIM:104300]: A form of Alzheimer disease, a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. It can be associated with cerebral amyloid angiopathy. Alzheimer disease can be associated with cerebral amyloid angiopathy. {ECO:0000269|PubMed:10097173, ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:10665499, ECO:0000269|PubMed:10677483, ECO:0000269|PubMed:10867787, ECO:0000269|PubMed:11063718, ECO:0000269|PubMed:11311152, ECO:0000269|PubMed:11528419, ECO:0000269|PubMed:12034808, ECO:0000269|PubMed:1302033, ECO:0000269|PubMed:1303239, ECO:0000269|PubMed:1303275, ECO:0000269|PubMed:1415269, ECO:0000269|PubMed:1465129, ECO:0000269|PubMed:15201367, ECO:0000269|PubMed:15365148, ECO:0000269|PubMed:15668448, ECO:0000269|PubMed:1671712, ECO:0000269|PubMed:1678058, ECO:0000269|PubMed:1908231, ECO:0000269|PubMed:1925564, ECO:0000269|PubMed:1944558, ECO:0000269|PubMed:8267572, ECO:0000269|PubMed:8290042, ECO:0000269|PubMed:8476439, ECO:0000269|PubMed:8577393, ECO:0000269|PubMed:8886002, ECO:0000269|PubMed:9328472, ECO:0000269|PubMed:9754958}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cerebral amyloid angiopathy, APP-related (CAA-APP) [MIM:605714]: A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. {ECO:0000269|PubMed:11409420, ECO:0000269|PubMed:12654973, ECO:0000269|PubMed:16178030, ECO:0000269|PubMed:20697050, ECO:0000269|PubMed:2111584}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 synapses 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 peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. 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: [Amyloid-beta protein 42]: More effective reductant than amyloid-beta protein 40. May activate mononuclear phagocytes in the brain and elicit inflammatory responses.; 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.
uniprot
proteins
mass_dalton
86943
uniprot
proteins
mutagenesis
MUTAGEN 99..102; /note="KRGR->NQGG: Reduced heparin-binding."; /evidence="ECO:0000269|PubMed:8158260"; MUTAGEN 108; /note="H->A: Loss of the copper binding site in the GFLD subdomain; when associated with A-110."; /evidence="ECO:0000269|PubMed:25122912"; MUTAGEN 110; /note="H->A: Loss of the copper binding site in the GFLD subdomain; when associated with A-108."; /evidence="ECO:0000269|PubMed:25122912"; MUTAGEN 137; /note="H->N: Binds copper. Forms dimer."; /evidence="ECO:0000269|PubMed:7913895"; MUTAGEN 141; /note="M->T: Binds copper. Forms dimer."; /evidence="ECO:0000269|PubMed:7913895"; MUTAGEN 144; /note="C->S: Binds copper. No dimer formation. No copper reducing activity."; /evidence="ECO:0000269|PubMed:10461923, ECO:0000269|PubMed:7913895"; MUTAGEN 147..149; /note="HLH->ALA: 50% decrease in copper reducing activity."; /evidence="ECO:0000269|PubMed:10461923"; MUTAGEN 147; /note="H->A: Loss of a copper binding site; when associated with A-151."; /evidence="ECO:0000269|PubMed:25122912"; MUTAGEN 147; /note="H->A: Some decrease in copper reducing activity."; /evidence="ECO:0000269|PubMed:11784781, ECO:0000269|PubMed:7913895"; MUTAGEN 147; /note="H->N: Binds copper. Forms dimer."; /evidence="ECO:0000269|PubMed:11784781, ECO:0000269|PubMed:7913895"; MUTAGEN 147; /note="H->Y: Greatly reduced copper-mediated low-density lipoprotein oxidation."; /evidence="ECO:0000269|PubMed:11784781, ECO:0000269|PubMed:7913895"; MUTAGEN 151; /note="H->A: Loss of a copper binding site; when associated with A-147."; /evidence="ECO:0000269|PubMed:25122912"; MUTAGEN 151; /note="H->K: Greatly reduced copper-mediated low-density lipoprotein oxidation."; /evidence="ECO:0000269|PubMed:11784781, ECO:0000269|PubMed:7913895"; MUTAGEN 151; /note="H->N: Binds copper. Forms dimer."; /evidence="ECO:0000269|PubMed:11784781, ECO:0000269|PubMed:7913895"; MUTAGEN 198; /note="S->A: Greatly reduced casein kinase phosphorylation."; /evidence="ECO:0000269|PubMed:10806211, ECO:0000269|PubMed:8999878"; MUTAGEN 206; /note="S->A: Reduced casein kinase phosphorylation."; /evidence="ECO:0000269|PubMed:10806211, ECO:0000269|PubMed:8999878"; MUTAGEN 499; /note="R->A: Reduced affinity for heparin; when associated with A-503."; /evidence="ECO:0000269|PubMed:15304215"; MUTAGEN 503; /note="K->A: Reduced affinity for heparin; when associated with A-499."; /evidence="ECO:0000269|PubMed:15304215"; MUTAGEN 656; /note="S->A: Abolishes chondroitin sulfate binding in L-APP733 isoform."; /evidence="ECO:0000269|PubMed:7737970"; MUTAGEN 676; /note="R->G: 60-70% zinc-induced amyloid-beta protein 28 aggregation."; /evidence="ECO:0000269|PubMed:10413512"; MUTAGEN 681; /note="Y->F: 60-70% zinc-induced amyloid-beta protein 28 aggregation."; /evidence="ECO:0000269|PubMed:10413512"; MUTAGEN 684; /note="H->R: Only 23% zinc-induced amyloid-beta protein 28 aggregation."; /evidence="ECO:0000269|PubMed:10413512"; MUTAGEN 695; /note="V->C: Causes formation of an artifactual disulfide bond with PSEN1."; /evidence="ECO:0000269|PubMed:30630874"; MUTAGEN 704; /note="G->V: Reduced protein oxidation. No hippocampal neuron toxicity."; MUTAGEN 706; /note="M->L: Reduced lipid peroxidation inhibition."; /evidence="ECO:0000269|PubMed:10535332, ECO:0000269|PubMed:9168929"; MUTAGEN 706; /note="M->V: No free radical production. No hippocampal neuron toxicity."; /evidence="ECO:0000269|PubMed:10535332, ECO:0000269|PubMed:9168929"; MUTAGEN 717; /note="V->C,S: Unchanged amyloid-beta protein 42/total amyloid-beta ratio."; /evidence="ECO:0000269|PubMed:8886002"; MUTAGEN 717; /note="V->K: Decreased amyloid-beta protein 42/total amyloid-beta ratio."; /evidence="ECO:0000269|PubMed:8886002"; MUTAGEN 717; /note="V->M: Increased amyloid-beta protein 42/40 ratio. No change in apoptosis after caspase cleavage."; /evidence="ECO:0000269|PubMed:8886002"; MUTAGEN 728; /note="Y->A: No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in amyloid-beta protein 42 secretion."; /evidence="ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:8887653, ECO:0000269|PubMed:9843960"; MUTAGEN 739; /note="D->A: No cleavage by caspases during apoptosis."; /evidence="ECO:0000269|PubMed:10319819, ECO:0000269|PubMed:10742146, ECO:0000269|PubMed:12214090"; MUTAGEN 739; /note="D->N: No effect on FADD-induced apoptosis."; /evidence="ECO:0000269|PubMed:10319819, ECO:0000269|PubMed:10742146, ECO:0000269|PubMed:12214090"; MUTAGEN 743; /note="T->A: Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension. Loss of phosphorylation by LRRK2."; /evidence="ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218, ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:28720718"; MUTAGEN 743; /note="T->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation."; /evidence="ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218, ECO:0000269|PubMed:11877420"; MUTAGEN 756; /note="G->A: APP internalization unchanged. No change in amyloid-beta protein 42 secretion."; /evidence="ECO:0000269|PubMed:10383380"; MUTAGEN 757..762; /note="YENPTY->AENPTA: No effect on C99 interaction with SORL1."; /evidence="ECO:0000269|PubMed:16407538"; MUTAGEN 757; /note="Y->A: Little APP internalization. Reduced amyloid-beta protein 42 secretion."; /evidence="ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:8887653"; MUTAGEN 757; /note="Y->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1."; /evidence="ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:8887653"; MUTAGEN 759; /note="N->A: No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced amyloid-beta protein 42 secretion."; /evidence="ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:8887653"; MUTAGEN 760; /note="P->A: Little APP internalization. Reduced amyloid-beta protein 42 secretion."; /evidence="ECO:0000269|PubMed:10383380"; MUTAGEN 762; /note="Y->A: Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in amyloid-beta protein 42 secretion."; /evidence="ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:8887653
uniprot
proteins
post_translational_modification
PTM: Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro) (PubMed:30630874). Amyloid-beta protein 40 and Amyloid-beta protein 42 are cleaved by ACE (PubMed:11604391, PubMed:16154999). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686. {ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:11604391, ECO:0000269|PubMed:16154999, ECO:0000269|PubMed:30630874}.; PTM: Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides. {ECO:0000269|PubMed:10319819}.; PTM: N-glycosylated (PubMed:2900137). N- and O-glycosylated (PubMed:2649245). O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:21712440, ECO:0000269|PubMed:22576872, ECO:0000269|PubMed:2649245, ECO:0000269|PubMed:2900137}.; PTM: Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (PubMed:10341243). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (PubMed:10341243). Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta (PubMed:11146006, PubMed:8131745). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (PubMed:11517218). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (PubMed:11877420). Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin (PubMed:8999878). {ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218, ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:8131745, ECO:0000269|PubMed:8999878}.; PTM: Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.; PTM: Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).; PTM: Amyloid-beta peptides are degraded by IDE. {ECO:0000250|UniProtKB:P12023}.; PTM: Sulfated on tyrosine residues. {ECO:0000269|PubMed:2649245}.
uniprot
proteins
protein_family
APP family
uniprot
proteins
pubmed
10081969
uniprot
proteins
pubmed
10097173
uniprot
proteins
pubmed
10201399
uniprot
proteins
pubmed
10319819
uniprot
proteins
pubmed
10341243
uniprot
proteins
pubmed
10383380
uniprot
proteins
pubmed
10413512
uniprot
proteins
pubmed
10461923
uniprot
proteins
pubmed
10535332
uniprot
proteins
pubmed
10631141
uniprot
proteins
pubmed
10656250
uniprot
proteins
pubmed
10665499
uniprot
proteins
pubmed
10677483
uniprot
proteins
pubmed
10681545
uniprot
proteins
pubmed
10742146
uniprot
proteins
pubmed
10806211
uniprot
proteins
pubmed
10816430
uniprot
proteins
pubmed
10821838
uniprot
proteins
pubmed
10830953
uniprot
proteins
pubmed
10867787
uniprot
proteins
pubmed
10940221
uniprot
proteins
pubmed
10940222
uniprot
proteins
pubmed
11063718
uniprot
proteins
pubmed
11146006
uniprot
proteins
pubmed
11238726
uniprot
proteins
pubmed
11274207
uniprot
proteins
pubmed
11278849
uniprot
proteins
pubmed
11311152
uniprot
proteins
pubmed
11409420
uniprot
proteins
pubmed
11438549
uniprot
proteins
pubmed
11517218
uniprot
proteins
pubmed
11528419
uniprot
proteins
pubmed
11544248
uniprot
proteins
pubmed
11604391
uniprot
proteins
pubmed
11689470
uniprot
proteins
pubmed
11724784
uniprot
proteins
pubmed
11775062
uniprot
proteins
pubmed
11784781
uniprot
proteins
pubmed
11851430
uniprot
proteins
pubmed
11877420
uniprot
proteins
pubmed
11943163
uniprot
proteins
pubmed
12032279
uniprot
proteins
pubmed
12034808
uniprot
proteins
pubmed
12142279
uniprot
proteins
pubmed
12214090
uniprot
proteins
pubmed
12611883
uniprot
proteins
pubmed
12654973
uniprot
proteins
pubmed
12665801
uniprot
proteins
pubmed
12859342
uniprot
proteins
pubmed
1302033
uniprot
proteins
pubmed
1303239
uniprot
proteins
pubmed
1303275
uniprot
proteins
pubmed
1307241
uniprot
proteins
pubmed
1363811
uniprot
proteins
pubmed
1406936
uniprot
proteins
pubmed
1415269
uniprot
proteins
pubmed
14527950
uniprot
proteins
pubmed
1465129
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15084524
uniprot
proteins
pubmed
15201367
uniprot
proteins
pubmed
15304215
uniprot
proteins
pubmed
15347684
uniprot
proteins
pubmed
15365148
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15668448
uniprot
proteins
pubmed
1587857
uniprot
proteins
pubmed
16154999
uniprot
proteins
pubmed
16174740
uniprot
proteins
pubmed
16178030
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16407538
uniprot
proteins
pubmed
1671712
uniprot
proteins
pubmed
1678058
uniprot
proteins
pubmed
16816112
uniprot
proteins
pubmed
17051221
uniprot
proteins
pubmed
17062754
uniprot
proteins
pubmed
1718421
uniprot
proteins
pubmed
17239395
uniprot
proteins
pubmed
17855360
uniprot
proteins
pubmed
17895381
uniprot
proteins
pubmed
17909280
uniprot
proteins
pubmed
18468999
uniprot
proteins
pubmed
1908231
uniprot
proteins
pubmed
1908403
uniprot
proteins
pubmed
19225519
uniprot
proteins
pubmed
1925564
uniprot
proteins
pubmed
19366692
uniprot
proteins
pubmed
1944558
uniprot
proteins
pubmed
1969731
uniprot
proteins
pubmed
19901339
uniprot
proteins
pubmed
19923222
uniprot
proteins
pubmed
20212142
uniprot
proteins
pubmed
20580937
uniprot
proteins
pubmed
20697050
uniprot
proteins
pubmed
20811458
uniprot
proteins
pubmed
2110105
uniprot
proteins
pubmed
2111584
uniprot
proteins
pubmed
2125487
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21712440
uniprot
proteins
pubmed
22457725
uniprot
proteins
pubmed
22576872
uniprot
proteins
pubmed
22584060
uniprot
proteins
pubmed
22654059
uniprot
proteins
pubmed
23011729
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24336208
uniprot
proteins
pubmed
24523320
uniprot
proteins
pubmed
2506449
uniprot
proteins
pubmed
25122912
uniprot
proteins
pubmed
25168729
uniprot
proteins
pubmed
2538123
uniprot
proteins
pubmed
2569763
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
2649245
uniprot
proteins
pubmed
2675837
uniprot
proteins
pubmed
26898943
uniprot
proteins
pubmed
2783775
uniprot
proteins
pubmed
28570778
uniprot
proteins
pubmed
28720718
uniprot
proteins
pubmed
2881207
uniprot
proteins
pubmed
28882996
uniprot
proteins
pubmed
2893289
uniprot
proteins
pubmed
2893290
uniprot
proteins
pubmed
2893291
uniprot
proteins
pubmed
2893379
uniprot
proteins
pubmed
2900137
uniprot
proteins
pubmed
29282295
uniprot
proteins
pubmed
2949367
uniprot
proteins
pubmed
3035574
uniprot
proteins
pubmed
30630874
uniprot
proteins
pubmed
3140222
uniprot
proteins
pubmed
3312495
uniprot
proteins
pubmed
3597385
uniprot
proteins
pubmed
3810169
uniprot
proteins
pubmed
38110576
uniprot
proteins
pubmed
7516706
uniprot
proteins
pubmed
7588758
uniprot
proteins
pubmed
7737970
uniprot
proteins
pubmed
7913895
uniprot
proteins
pubmed
8109908
uniprot
proteins
pubmed
8131745
uniprot
proteins
pubmed
8154870
uniprot
proteins
pubmed
8158260
uniprot
proteins
pubmed
8229004
uniprot
proteins
pubmed
8248178
uniprot
proteins
pubmed
8267572
uniprot
proteins
pubmed
8290042
uniprot
proteins
pubmed
8344894
uniprot
proteins
pubmed
8446172
uniprot
proteins
pubmed
8476439
uniprot
proteins
pubmed
8576160
uniprot
proteins
pubmed
8577393
uniprot
proteins
pubmed
8626687
uniprot
proteins
pubmed
8855266
uniprot
proteins
pubmed
8886002
uniprot
proteins
pubmed
8887653
uniprot
proteins
pubmed
8973180
uniprot
proteins
pubmed
8999878
uniprot
proteins
pubmed
9108164
uniprot
proteins
pubmed
9168929
uniprot
proteins
pubmed
9300481
uniprot
proteins
pubmed
9328472
uniprot
proteins
pubmed
9338779
uniprot
proteins
pubmed
9357988
uniprot
proteins
pubmed
9585534
uniprot
proteins
pubmed
9693002
uniprot
proteins
pubmed
9754958
uniprot
proteins
pubmed
9843960
uniprot
proteins
pubmed
9890987
uniprot
proteins
sequence_length
770
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:20580937, ECO:0000269|PubMed:2649245, ECO:0000305|PubMed:25122912}; Single-pass type I membrane protein {ECO:0000269|PubMed:30630874, ECO:0000305|PubMed:10383380, ECO:0000305|PubMed:25122912}. Membrane {ECO:0000269|PubMed:2900137, ECO:0000305|PubMed:22584060}; Single-pass type I membrane protein {ECO:0000269|PubMed:2900137, ECO:0000269|PubMed:30630874, ECO:0000305|PubMed:22584060}. Perikaryon {ECO:0000269|PubMed:10341243}. Cell projection, growth cone {ECO:0000269|PubMed:10341243}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:20580937}. Early endosome {ECO:0000269|PubMed:20580937}. Cytoplasmic vesicle {ECO:0000269|PubMed:20580937, ECO:0000269|PubMed:25122912}. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles (PubMed:20580937). During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body (PubMed:10341243). Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions. {ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:20580937}.; SUBCELLULAR LOCATION: [C83]: Endoplasmic reticulum {ECO:0000269|PubMed:14527950}. Golgi apparatus {ECO:0000269|PubMed:14527950}. Early endosome {ECO:0000269|PubMed:14527950}.; SUBCELLULAR LOCATION: [C99]: Early endosome {ECO:0000269|PubMed:14527950}.; SUBCELLULAR LOCATION: [Soluble APP-beta]: Secreted {ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:2649245}.; SUBCELLULAR LOCATION: [Amyloid-beta protein 40]: Cell surface {ECO:0000269|PubMed:16154999}.; SUBCELLULAR LOCATION: [Amyloid-beta protein 42]: Cell surface {ECO:0000269|PubMed:11689470, ECO:0000269|PubMed:16154999}. Note=Associates with FPR2 at the cell surface and the complex is then rapidly internalized. {ECO:0000269|PubMed:11689470}.; SUBCELLULAR LOCATION: [Gamma-secretase C-terminal fragment 59]: Nucleus {ECO:0000269|PubMed:11544248}. Cytoplasm {ECO:0000269|PubMed:11544248}. Note=Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65) (PubMed:11544248). In dopaminergic neurons, the phosphorylated Thr-743 form is localized to the nucleus (By similarity). {ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:11544248}.
uniprot
proteins
transmembrane_region
TRANSMEM 702..722; /note="Helical"; /evidence="ECO:0000305|PubMed:22584060, ECO:0000305|PubMed:22654059, ECO:0000305|PubMed:30630874
uniprot
proteins