Human Gene APP (ENST00000346798.8) from GENCODE V44
Description: Homo sapiens amyloid beta precursor protein (APP), transcript variant 11, mRNA. (from RefSeq NM_001385253) RefSeq Summary (NM_000484): This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2014]. Gencode Transcript: ENST00000346798.8 Gencode Gene: ENSG00000142192.22 Transcript (Including UTRs) Position: hg38 chr21:25,880,550-26,170,770 Size: 290,221 Total Exon Count: 18 Strand: - Coding Region Position: hg38 chr21:25,881,670-26,170,620 Size: 288,951 Coding Exon Count: 18
ID:A4_HUMAN DESCRIPTION: RecName: Full=Amyloid beta A4 protein; AltName: Full=ABPP; AltName: Full=APPI; Short=APP; AltName: Full=Alzheimer disease amyloid protein; AltName: Full=Cerebral vascular amyloid peptide; Short=CVAP; AltName: Full=PreA4; AltName: Full=Protease nexin-II; Short=PN-II; Contains: RecName: Full=N-APP; Contains: RecName: Full=Soluble APP-alpha; Short=S-APP-alpha; Contains: RecName: Full=Soluble APP-beta; Short=S-APP-beta; Contains: RecName: Full=C99; Contains: RecName: Full=Beta-amyloid protein 42; AltName: Full=Beta-APP42; Contains: RecName: Full=Beta-amyloid protein 40; AltName: Full=Beta-APP40; Contains: RecName: Full=C83; Contains: RecName: Full=P3(42); Contains: RecName: Full=P3(40); Contains: RecName: Full=C80; Contains: RecName: Full=Gamma-secretase C-terminal fragment 59; AltName: Full=Amyloid intracellular domain 59; Short=AICD-59; Short=AID(59); AltName: Full=Gamma-CTF(59); Contains: RecName: Full=Gamma-secretase C-terminal fragment 57; AltName: Full=Amyloid intracellular domain 57; Short=AICD-57; Short=AID(57); AltName: Full=Gamma-CTF(57); Contains: RecName: Full=Gamma-secretase C-terminal fragment 50; AltName: Full=Amyloid intracellular domain 50; Short=AICD-50; Short=AID(50); AltName: Full=Gamma-CTF(50); Contains: RecName: Full=C31; Flags: Precursor; FUNCTION: 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. FUNCTION: Beta-amyloid 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. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts. FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity). 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). SUBUNIT: Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity). Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, FPRL1, APPBP1, IB1, KNS2 (via its TPR domains) (By similarity), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1. Amyloid beta-42 binds CHRNA7 in hippocampal neurons. Beta-amyloid associates with HADH2. Soluble APP binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER (By similarity). Interacts with ANKS1B and TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; this is promoted by heparin binding. Beta-amyloid protein 40 interacts with S100A9. INTERACTION: Self; NbExp=2; IntAct=EBI-821758, EBI-821758; P31696:AGRN (xeno); NbExp=3; IntAct=EBI-2431589, EBI-457650; Q02410:APBA1; NbExp=3; IntAct=EBI-77613, EBI-368690; O00213:APBB1; NbExp=5; IntAct=EBI-77613, EBI-81694; Q92870:APBB2; NbExp=2; IntAct=EBI-77613, EBI-79277; P51693:APLP1; NbExp=2; IntAct=EBI-302641, EBI-74648; Q06481:APLP2; NbExp=2; IntAct=EBI-302641, EBI-79306; P02647:APOA1; NbExp=5; IntAct=EBI-77613, EBI-701692; Q13867:BLMH; NbExp=2; IntAct=EBI-302641, EBI-718504; P39060:COL18A1; NbExp=2; IntAct=EBI-821758, EBI-2566375; O75955:FLOT1; NbExp=5; IntAct=EBI-77613, EBI-603643; P01100:FOS; NbExp=3; IntAct=EBI-77613, EBI-852851; Q9NSC5:HOMER3; NbExp=3; IntAct=EBI-302661, EBI-748420; Q99714:HSD17B10; NbExp=4; IntAct=EBI-77613, EBI-79964; O43736:ITM2A; NbExp=3; IntAct=EBI-302641, EBI-2431769; P05412:JUN; NbExp=2; IntAct=EBI-77613, EBI-852823; Q9UQF2:MAPK8IP1; NbExp=4; IntAct=EBI-77613, EBI-78404; Q9WVI9-1:Mapk8ip1 (xeno); NbExp=2; IntAct=EBI-77613, EBI-288461; P10636:MAPT; NbExp=9; IntAct=EBI-77613, EBI-366182; P03897:MT-ND3; NbExp=2; IntAct=EBI-821758, EBI-1246249; P21359:NF1; NbExp=3; IntAct=EBI-77613, EBI-1172917; P08138:NGFR; NbExp=4; IntAct=EBI-77613, EBI-1387782; P07174:Ngfr (xeno); NbExp=2; IntAct=EBI-2431589, EBI-1038810; P61457:PCBD1; NbExp=2; IntAct=EBI-77613, EBI-740475; P30101:PDIA3; NbExp=3; IntAct=EBI-77613, EBI-979862; Q13526:PIN1; NbExp=2; IntAct=EBI-302641, EBI-714158; P49768:PSEN1; NbExp=6; IntAct=EBI-77613, EBI-297277; P29353:SHC1; NbExp=5; IntAct=EBI-77613, EBI-78835; Q92529:SHC3; NbExp=2; IntAct=EBI-77613, EBI-79084; Q9NP59:SLC40A1; NbExp=4; IntAct=EBI-77613, EBI-725153; Q8BGY9:Slc5a7 (xeno); NbExp=2; IntAct=EBI-77613, EBI-2010752; Q9HCB6:SPON1; NbExp=3; IntAct=EBI-302641, EBI-2431846; P01137:TGFB1; NbExp=2; IntAct=EBI-77613, EBI-779636; P61812:TGFB2; NbExp=6; IntAct=EBI-77613, EBI-779581; O75509:TNFRSF21; NbExp=3; IntAct=EBI-77613, EBI-2313231; Q13625:TP53BP2; NbExp=3; IntAct=EBI-77613, EBI-77642; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. Membrane, clathrin-coated pit. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. 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. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. 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. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. TISSUE SPECIFICITY: Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex- opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra- striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non- neuronal cells. Isoform APP751 is the most abundant form in T- lymphocytes. Appican is expressed in astrocytes. INDUCTION: Increased levels during neuronal differentiation. DOMAIN: The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells. DOMAIN: The NPXY sequence motif found in many tyrosine- phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C- terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The NPXY site is also involved in clathrin-mediated endocytosis. 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 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many other minor beta-amyloid peptides, beta-amyloid 1-X peptides, are found in cerebral spinal fluid (CSF) including the beta-amyloid X- 15 peptides, produced from the cleavage by alpha-secretase and all terminatiing at Gln-686. PTM: Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of beta-amyloid peptides. PTM: N- and O-glycosylated. 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 beta-amyloid peptides (beta-amyloid 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on beta-amyloid 38, beta-amyloid 40 nor on beta-amyloid 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. PTM: Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. 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. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin. 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 beta-amyloid-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: Beta-amyloid peptides are degraded by IDE. MASS SPECTROMETRY: Mass=6461.6; Method=MALDI; Range=712-767; Source=PubMed:12214090; MASS SPECTROMETRY: Mass=6451.6; Method=MALDI; Range=714-770; Source=PubMed:12214090; MASS SPECTROMETRY: Mass=6436.8; Method=MALDI; Range=715-769; Source=PubMed:12214090; MASS SPECTROMETRY: Mass=5752.5; Method=MALDI; Range=719-767; Source=PubMed:12214090; DISEASE: Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:104300]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is 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 constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C- terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. DISEASE: Defects in APP are the cause of 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. MISCELLANEOUS: Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding. SIMILARITY: Belongs to the APP family. SIMILARITY: Contains 1 BPTI/Kunitz inhibitor domain. SEQUENCE CAUTION: Sequence=AAA58727.1; Type=Miscellaneous discrepancy; Note=Contamination by an Alu repeat; WEB RESOURCE: Name=Alzheimer Research Forum; Note=APP mutations; URL="http://www.alzforum.org/res/com/mut/app/default.asp"; WEB RESOURCE: Name=AD mutations; URL="http://www.molgen.ua.ac.be/ADmutations/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/APP"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/app/"; WEB RESOURCE: Name=Wikipedia; Note=Amyloid beta entry; URL="http://en.wikipedia.org/wiki/Amyloid_beta";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05067
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LF210650 - JP 2014500723-A/18153: Polycomb-Associated Non-Coding RNAs. MA446227 - JP 2018138019-A/18153: Polycomb-Associated Non-Coding RNAs. JA482018 - Sequence 1 from Patent WO2011072091. JA482019 - Sequence 2 from Patent WO2011072091. JA482020 - Sequence 3 from Patent WO2011072091. JA482021 - Sequence 4 from Patent WO2011072091. JA482022 - Sequence 5 from Patent WO2011072091. JE980310 - Sequence 1 from Patent EP2862929. JE980311 - Sequence 2 from Patent EP2862929. JE980312 - Sequence 3 from Patent EP2862929. JE980313 - Sequence 4 from Patent EP2862929. JE980314 - Sequence 5 from Patent EP2862929. LF385141 - JP 2014500723-A/192644: Polycomb-Associated Non-Coding RNAs. MA620718 - JP 2018138019-A/192644: Polycomb-Associated Non-Coding RNAs. LF385472 - JP 2014500723-A/192975: Polycomb-Associated Non-Coding RNAs. MA621049 - JP 2018138019-A/192975: Polycomb-Associated Non-Coding RNAs. A02759 - H.sapiens mRNA for amyloid plaque core protein. Y00264 - Human mRNA for amyloid A4 precursor of Alzheimer's disease. BC065529 - Homo sapiens amyloid beta (A4) precursor protein, mRNA (cDNA clone MGC:75167 IMAGE:6152423), complete cds. LF214042 - JP 2014500723-A/21545: Polycomb-Associated Non-Coding RNAs. MA449619 - JP 2018138019-A/21545: Polycomb-Associated Non-Coding RNAs. AF282245 - Homo sapiens amyloid precursor protein 639 (APP639) mRNA, complete cds. BC065523 - Homo sapiens amyloid beta (A4) precursor protein, mRNA (cDNA clone IMAGE:6007573), containing frame-shift errors. M18734 - Human beta-amyloid A4 mRNA, partial cds. X06989 - Homo sapiens mRNA for amyloid A4 protein (APP gene). AK297412 - Homo sapiens cDNA FLJ54261 complete cds, highly similar to Homo sapiens amyloid beta (A4) precursor protein, transcript variant 3, mRNA. M16765 - Human cerebrovascular and neuritic plaque amyloid beta-protein mRNA, 3' end. AK295373 - Homo sapiens cDNA FLJ50525 complete cds, highly similar to Amyloid beta A4 protein precursor (APP) (ABPP) (Alzheimer disease amyloid protein homolog) [Contains: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); Gamma-CTF(59) (Gamma-secretase C-terminal fragment 59); Gamma-CTF(57) (Gamma-secretase C-terminal fragment 57); Gamma-CTF(50) (Gamma- secretase C-terminal fragment 50); C31]. AK296229 - Homo sapiens cDNA FLJ59550 complete cds, highly similar to Homo sapiens amyloid beta (A4) precursor protein, transcript variant 3, mRNA. AK295621 - Homo sapiens cDNA FLJ50531 complete cds, highly similar to Amyloid beta A4 protein precursor (APP) (ABPP)(Alzheimer disease amyloid protein homolog) [Contains: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); Gamma-CTF(59) (Gamma-secretaseC-terminal fragment 59); Gamma-CTF(57) (Gamma-secretaseC-terminal fragment 57); Gamma-CTF(50) (Gamma- secretaseC-terminal fragment 50); C31]. AK294534 - Homo sapiens cDNA FLJ50491 complete cds, highly similar to Amyloid beta A4 protein precursor (APP) (ABPP)(Alzheimer disease amyloid protein) (Cerebral vascularamyloid peptide) (CVAP) (Protease nexin-II) (PN-II)(APPI) (PreA4) [Contains: Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99; Beta-amyloidprotein 42 (Beta-APP42); Beta-amyloid protein 40(Beta-APP40); C83; P3(42); P3(40); Gamma-CTF(59)(Gamma-secretase C-terminal fragment 59) (Amyloidintracellular domain 59) (AID(59)); Gamma-CTF(57)(Gamma- secretase C-terminal fragment 57) (Amyloidintracellular domain 57) (AID(57)); Gamma-CTF(50)(Gamma-secretase C-terminal fragment 50) (Amyloidintracellular domain 50) (AID(50)); C31]. AK297229 - Homo sapiens cDNA FLJ54367 complete cds, highly similar to Amyloid beta A4 protein precursor (APP) (ABPP)(Alzheimer disease amyloid protein homolog) [Contains: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); Gamma-CTF(59) (Gamma-secretaseC-terminal fragment 59); Gamma-CTF(57) (Gamma-secretaseC-terminal fragment 57); Gamma-CTF(50) (Gamma- secretaseC-terminal fragment 50); C31]. AK298861 - Homo sapiens cDNA FLJ51942 complete cds, highly similar to Homo sapiens amyloid beta (A4) precursor protein, transcript variant 3, mRNA. HM005315 - Homo sapiens clone HTL-T-2 testicular tissue protein Li 2 mRNA, complete cds. E02400 - DNA encoding NAP(new senile plaque amyloid precursor protein having protease inhibitor). AK312326 - Homo sapiens cDNA, FLJ92638, Homo sapiens amyloid beta (A4) precursor protein (proteasenexin-II, Alzheimer disease) (APP), mRNA. EU832797 - Synthetic construct Homo sapiens clone HAIB:100067826; DKFZo008D0433 amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) protein (APP) gene, encodes complete protein. GQ129348 - Synthetic construct Homo sapiens clone HAIB:100068486; DKFZo004D0434 amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) protein (APP) gene, partial cds. AB384791 - Synthetic construct DNA, clone: pF1KB3334, Homo sapiens APP gene for amyloid beta A4 protein precursor, complete cds, without stop codon, in Flexi system. M28373 - Homo sapiens amyloid protein A4 precursor mRNA, 3' end of cds. BC004369 - Homo sapiens amyloid beta (A4) precursor protein, mRNA (cDNA clone IMAGE:3639599), complete cds. KJ901289 - Synthetic construct Homo sapiens clone ccsbBroadEn_10683 APP gene, encodes complete protein. AK311717 - Homo sapiens cDNA, FLJ18759. JD112573 - Sequence 93597 from Patent EP1572962. S41243 - amyloid protein precursor {3' region, alternative polyadenylation, long mRNA} [human, brain, mRNA Partial, 337 nt]. JD045620 - Sequence 26644 from Patent EP1572962. JD504198 - Sequence 485222 from Patent EP1572962. JD087959 - Sequence 68983 from Patent EP1572962. LF339737 - JP 2014500723-A/147240: Polycomb-Associated Non-Coding RNAs. MA575314 - JP 2018138019-A/147240: Polycomb-Associated Non-Coding RNAs. S41242 - amyloid protein precursor {3' region, alternative polyadenylation, short mRNA} [human, brain, mRNA Partial, 80 nt]. M15533 - Human amyloid protein (AD-AP) mRNA, 3' end. LF339738 - JP 2014500723-A/147241: Polycomb-Associated Non-Coding RNAs. MA575315 - JP 2018138019-A/147241: Polycomb-Associated Non-Coding RNAs. JD428728 - Sequence 409752 from Patent EP1572962. JD482042 - Sequence 463066 from Patent EP1572962. JD498353 - Sequence 479377 from Patent EP1572962. JD435207 - Sequence 416231 from Patent EP1572962. LF339739 - JP 2014500723-A/147242: Polycomb-Associated Non-Coding RNAs. MA575316 - JP 2018138019-A/147242: Polycomb-Associated Non-Coding RNAs. LF339740 - JP 2014500723-A/147243: Polycomb-Associated Non-Coding RNAs. MA575317 - JP 2018138019-A/147243: Polycomb-Associated Non-Coding RNAs. LF339741 - JP 2014500723-A/147244: Polycomb-Associated Non-Coding RNAs. MA575318 - JP 2018138019-A/147244: Polycomb-Associated Non-Coding RNAs. S60721 - beta-amyloid peptide precursor {clone 1} [human, mRNA Partial Mutant, 246 nt]. S61380 - beta-amyloid peptide precursor {clone 2} [human, mRNA Partial Mutant, 246 nt]. S61383 - beta-amyloid peptide precursor {clone 3} [human, mRNA Partial Mutant, 246 nt]. AB066441 - Homo sapiens APP mRNA for amyloid precursor protein, partial cds, D678N mutant. LF339744 - JP 2014500723-A/147247: Polycomb-Associated Non-Coding RNAs. MA575321 - JP 2018138019-A/147247: Polycomb-Associated Non-Coding RNAs. M15532 - Human amyloid beta protein mRNA, partial cds. LF339745 - JP 2014500723-A/147248: Polycomb-Associated Non-Coding RNAs. MA575322 - JP 2018138019-A/147248: Polycomb-Associated Non-Coding RNAs. LF339750 - JP 2014500723-A/147253: Polycomb-Associated Non-Coding RNAs. MA575327 - JP 2018138019-A/147253: Polycomb-Associated Non-Coding RNAs. LF339752 - JP 2014500723-A/147255: Polycomb-Associated Non-Coding RNAs. MA575329 - JP 2018138019-A/147255: Polycomb-Associated Non-Coding RNAs. LF339756 - JP 2014500723-A/147259: Polycomb-Associated Non-Coding RNAs. MA575333 - JP 2018138019-A/147259: Polycomb-Associated Non-Coding RNAs. LF339757 - JP 2014500723-A/147260: Polycomb-Associated Non-Coding RNAs. MA575334 - JP 2018138019-A/147260: Polycomb-Associated Non-Coding RNAs. LF339759 - JP 2014500723-A/147262: Polycomb-Associated Non-Coding RNAs. MA575336 - JP 2018138019-A/147262: Polycomb-Associated Non-Coding RNAs. LF339760 - JP 2014500723-A/147263: Polycomb-Associated Non-Coding RNAs. MA575337 - JP 2018138019-A/147263: Polycomb-Associated Non-Coding RNAs. LF339761 - JP 2014500723-A/147264: Polycomb-Associated Non-Coding RNAs. MA575338 - JP 2018138019-A/147264: Polycomb-Associated Non-Coding RNAs. E03704 - cDNA encoding hybrid protein which is composed human KPI and human tPA signal peptide. X06981 - Human mRNA fragment for amyloid beta-protein (AP) insertion. E02405 - DNA encoding PI(the active region that has protease inhibitor activity of NAP). X06982 - Homo sapiens partial mRNA for amyloid beta-protein (APP gene). LF339762 - JP 2014500723-A/147265: Polycomb-Associated Non-Coding RNAs. MA575339 - JP 2018138019-A/147265: Polycomb-Associated Non-Coding RNAs. LF339763 - JP 2014500723-A/147266: Polycomb-Associated Non-Coding RNAs. MA575340 - JP 2018138019-A/147266: Polycomb-Associated Non-Coding RNAs. LF339765 - JP 2014500723-A/147268: Polycomb-Associated Non-Coding RNAs. MA575342 - JP 2018138019-A/147268: Polycomb-Associated Non-Coding RNAs. LF339768 - JP 2014500723-A/147271: Polycomb-Associated Non-Coding RNAs. MA575345 - JP 2018138019-A/147271: Polycomb-Associated Non-Coding RNAs. LF339774 - JP 2014500723-A/147277: Polycomb-Associated Non-Coding RNAs. MA575351 - JP 2018138019-A/147277: Polycomb-Associated Non-Coding RNAs. LF339781 - JP 2014500723-A/147284: Polycomb-Associated Non-Coding RNAs. MA575358 - JP 2018138019-A/147284: Polycomb-Associated Non-Coding RNAs. LF212681 - JP 2014500723-A/20184: Polycomb-Associated Non-Coding RNAs. MA448258 - JP 2018138019-A/20184: Polycomb-Associated Non-Coding RNAs. M35675 - Human amyloid beta precursor protein (ABPP) mRNA, 5' end. HW581691 - JP 2014513065-A/20: Effective Amounts of (3aR)-1,3a,8-Trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3 b]indol-5-yl Phenylcarbamate and Methods Thereof. JC442381 - Sequence 20 from Patent EP2683242. MA353526 - JP 2018076332-A/20: Effective Amounts of (3aR)-1,3a,8-Trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3 b]indol-5-yl Phenylcarbamate and Methods Thereof. JC442388 - Sequence 27 from Patent EP2683242. JD460697 - Sequence 441721 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa05010 - Alzheimer's disease
BioCarta from NCI Cancer Genome Anatomy Project h_plateletAppPathway - Platelet Amyloid Precursor Protein Pathway h_p35alzheimersPathway - Deregulation of CDK5 in Alzheimers Disease h_appPathway - Generation of amyloid b-peptide by PS1
Reactome (by CSHL, EBI, and GO)
Protein P05067 (Reactome details) participates in the following event(s):
R-HSA-5692495 BACE1 cleaves APP(18-770) to APP(18-671) and APP(672-770) R-HSA-8871494 SORL1 binds APP(18-770) R-HSA-5229132 AP4 binds APP R-HSA-481007 Exocytosis of platelet alpha granule contents R-HSA-391913 FPR2 binds FPR2 ligands R-HSA-879411 Advanced glycosylation end product-specific receptor (AGER/RAGE) is a multiligand receptor R-HSA-5229111 AP4 transports APP from trans-Golgi network to endosome lumen R-HSA-8871506 SORL1 transports APP(18-770) from endosome lumen to Golgi lumen R-HSA-749454 The Ligand:GPCR:Gi complex dissociates R-HSA-749452 The Ligand:GPCR:Gq complex dissociates R-HSA-879362 AGER binds ERK1/2 R-NUL-997411 AGER binds rat ERK1/2 R-HSA-8952289 FAM20C phosphorylates FAM20C substrates R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi R-HSA-749448 Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi R-HSA-379048 Liganded Gq/11-activating GPCRs act as GEFs for Gq/11 R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-977225 Amyloid fiber formation R-HSA-432720 Lysosome Vesicle Biogenesis R-HSA-114608 Platelet degranulation R-HSA-844456 The NLRP3 inflammasome R-HSA-444473 Formyl peptide receptors bind formyl peptides and many other ligands R-HSA-879415 Advanced glycosylation endproduct receptor signaling R-HSA-8863678 Neurodegenerative Diseases R-HSA-392499 Metabolism of proteins R-HSA-421837 Clathrin derived vesicle budding R-HSA-76005 Response to elevated platelet cytosolic Ca2+ R-HSA-622312 Inflammasomes R-HSA-418594 G alpha (i) signalling events R-HSA-416476 G alpha (q) signalling events R-HSA-375276 Peptide ligand-binding receptors R-HSA-168249 Innate Immune System R-HSA-1643685 Disease R-HSA-199992 trans-Golgi Network Vesicle Budding R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8957275 Post-translational protein phosphorylation R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways R-HSA-388396 GPCR downstream signalling R-HSA-373076 Class A/1 (Rhodopsin-like receptors) R-HSA-168256 Immune System R-HSA-199991 Membrane Trafficking R-HSA-597592 Post-translational protein modification R-HSA-109582 Hemostasis R-HSA-372790 Signaling by GPCR R-HSA-500792 GPCR ligand binding R-HSA-5653656 Vesicle-mediated transport R-HSA-162582 Signal Transduction
US Server
