UniProtKB - P49768 (PSN1_HUMAN)
(max 400 entries)
Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the ‘basket’ to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
>sp|P49768|PSN1_HUMAN Presenilin-1 OS=Homo sapiens OX=9606 GN=PSEN1 PE=1 SV=1 MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYIOther tutorials and videosHelp videoFeedback
Protein
Presenilin-1
Gene
PSEN1
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:28269784, PubMed:20460383). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:25394380, PubMed:16959576). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).By similarity
<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toi
20 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.12"Purification and characterization of the human gamma-secretase complex."
Fraering P.C., Ye W., Strub J.-M., Dolios G., LaVoie M.J., Ostaszewski B.L., van Dorsselaer A., Wang R., Selkoe D.J., Wolfe M.S.
Biochemistry 43:9774-9789(2004) [PubMed] [Europe PMC] [Abstract] - Ref.17"Direct association of presenilin-1 with beta-catenin."
Murayama M., Tanaka S., Palacino J., Murayama O., Honda T., Sun X., Yasutake K., Nihonmatsu N., Wolozin B., Takashima A.
FEBS Lett. 433:73-77(1998) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CTNNB1, SUBCELLULAR LOCATION. - Ref.19"Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis."
Steiner H., Romig H., Pesold B., Philipp U., Baader M., Citron M., Loetscher H., Jacobsen H., Haass C.
Biochemistry 38:14600-14605(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, MUTAGENESIS OF MET-292, PROTEOLYTIC PROCESSING. - Ref.21"Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch."
Ray W.J., Yao M., Mumm J., Schroeter E.H., Saftig P., Wolfe M., Selkoe D.J., Kopan R., Goate A.M.
J. Biol. Chem. 274:36801-36807(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH. - Ref.23"Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity."
Wolfe M.S., Xia W., Ostaszewski B.L., Diehl T.S., Kimberly W.T., Selkoe D.J.
Nature 398:513-517(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF ASP-257 AND ASP-385. - Ref.24"Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling."
Berezovska O., Jack C., McLean P., Aster J.C., Hicks C., Xia W., Wolfe M.S., Kimberly W.T., Weinmaster G., Selkoe D.J., Hyman B.T.
J. Neurochem. 75:583-593(2000) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF ASP-257 AND ASP-385. - Ref.25"Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch."
Kulic L., Walter J., Multhaup G., Teplow D.B., Baumeister R., Romig H., Capell A., Steiner H., Haass C.
Proc. Natl. Acad. Sci. U.S.A. 97:5913-5918(2000) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF LEU-286. - Ref.27"A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions."
Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T., Robakis N.K.
EMBO J. 21:1948-1956(2002) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH CDH1 AND CTNNB1. - Ref.31"Reconstitution of gamma-secretase activity."
Edbauer D., Winkler E., Regula J.T., Pesold B., Steiner H., Haass C.
Nat. Cell Biol. 5:486-488(2003) [PubMed] [Europe PMC] [Abstract]Cited for: ENZYME ACTIVITY OF A GAMMA-SECRETASE COMPLEX, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT. - Ref.32"Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2."
Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S., Selkoe D.J.
Proc. Natl. Acad. Sci. U.S.A. 100:6382-6387(2003) [PubMed] [Europe PMC] [Abstract]Cited for: COMPONENT OF A GAMMA-SECRETASE COMPLEX WITH PEN2; PSEN1/PSEN2 AND NCSTN. - Ref.34"A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations."
Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.
J. Alzheimers Dis. 6:31-43(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT AD3 SER-117, CHARACTERIZATION OF VARIANTS AD3 LEU-117 AND SER-117. - Ref.37"Conserved residues within the putative active site of gamma-secretase differentially influence enzyme activity and inhibitor binding."
Wrigley J.D., Nunn E.J., Nyabi O., Clarke E.E., Hunt P., Nadin A., De Strooper B., Shearman M.S., Beher D.
J. Neurochem. 90:1312-1320(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, ACTIVE SITES ASP-257 AND ASP-385, MUTAGENESIS OF TYR-256; ASP-257; ASP-385 AND TYR-389. - Ref.40"Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations."
Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., Serneels L., De Strooper B., Yu G., Bezprozvanny I.
Cell 126:981-993(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT AD3 VAL-146. - Ref.41"C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation."
Wang J., Beher D., Nyborg A.C., Shearman M.S., Golde T.E., Goate A.
J. Neurochem. 96:218-227(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION OF PAL MOTIF, MUTAGENESIS OF PRO-433; ALA-434 AND LEU-435, CHARACTERIZATION OF VARIANT AD3 PHE-435. - Ref.52"G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH APH1 AND PEN2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT AD3 ASP-206. - Ref.54"Three-dimensional structure of human gamma-secretase."
Lu P., Bai X.C., Ma D., Xie T., Yan C., Sun L., Yang G., Zhao Y., Zhou R., Scheres S.H., Shi Y.
Nature 512:166-170(2014) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.5 ANGSTROMS), FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY. - Ref.56"An atomic structure of human gamma-secretase."
Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., Shi Y.
Nature 525:212-217(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS AD3 LEU-213; ILE-237 AND PHE-261, MUTAGENESIS OF ILE-202; LEU-226; LEU-248 AND LEU-424. - Ref.113"Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor."
Litterst C., Georgakopoulos A., Shioi J., Ghersi E., Wisniewski T., Wang R., Ludwig A., Robakis N.K.
J. Biol. Chem. 282:16155-16163(2007) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 LEU-117; LEU-146; GLU-246; VAL-260; LEU-264 AND GLY-280, FUNCTION, MUTAGENESIS OF ASP-257. - Ref.119"A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity."
Heilig E.A., Xia W., Shen J., Kelleher R.J. III
J. Biol. Chem. 285:22350-22359(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-435, CHARACTERIZATION OF VARIANTS AD3 PHE-435; GLN-436 AND SER-436, MUTAGENESIS OF PRO-433 AND LEU-435, FUNCTION. - Ref.134"A novel PSEN1 K311R mutation discovered in Chinese families with late-onset Alzheimer's disease affects amyloid-beta production and tau phosphorylation."
Dong J., Qin W., Wei C., Tang Y., Wang Q., Jia J.
J. Alzheimers Dis. 57:613-623(2017) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT ARG-311, CHARACTERIZATION OF VARIANTS ALA-280 AND ARG-311, FUNCTION.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei | 257 | 3 Publications <p>Manually curated information which has been inferred by a curator based on his/her scientific knowledge or on the scientific content of an article.</p> <p><a href="/manual/evidences#ECO:0000305">More...</a></p> Manual assertion inferred by curator fromi
| 1 | |
| Active sitei | 385 | 3 Publications Manual assertion inferred by curator fromi
| 1 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- aspartic endopeptidase activity, intramembrane cleaving Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayi
- aspartic-type endopeptidase activity Source: Reactome
- beta-catenin binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactioni
- cadherin binding Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestori
- calcium channel activity Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypei
- endopeptidase activity Source: MGIInferred from direct assayi
- PDZ domain binding Source: UniProtKBInferred from physical interactioni
GO - Biological processi
- activation of MAPKK activity Source: Ensembl
- amyloid-beta formation Source: UniProtKBInferred from mutant phenotypei
- amyloid precursor protein catabolic process Source: HGNC <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementi
- amyloid precursor protein metabolic process Source: UniProtKBInferred from direct assayi
- astrocyte activation Source: ARUK-UCL <p>Inferred from Genetic Interaction</p> <p>Used to describe “traditional” genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p> Inferred from genetic interactioni
- astrocyte activation involved in immune response Source: ARUK-UCLInferred from genetic interactioni
- autophagosome assembly Source: Ensembl
- blood vessel development Source: Ensembl
- brain morphogenesis Source: Ensembl
- Cajal-Retzius cell differentiation Source: Ensembl
- cell-cell adhesion Source: MGIInferred from mutant phenotypei
- cell fate specification Source: Ensembl
- cellular response to amyloid-beta Source: ARUK-UCLInferred from genetic interactioni
- cellular response to DNA damage stimulus Source: Ensembl
- cerebellum development Source: Ensembl
- cerebral cortex cell migration Source: Ensembl
- choline transport Source: Ensembl
- dorsal/ventral neural tube patterning Source: Ensembl
- embryonic limb morphogenesis Source: Ensembl
- endoplasmic reticulum calcium ion homeostasis Source: MGIInferred from direct assayi
- epithelial cell proliferation Source: Ensembl
- heart looping Source: Ensembl
- hematopoietic progenitor cell differentiation Source: Ensembl
- intracellular signal transduction Source: InterPro
- learning or memory Source: ARUK-UCLInferred from genetic interactioni
- membrane protein ectodomain proteolysis Source: HGNCInferred from direct assayi
- memory Source: ARUK-UCLInferred from genetic interactioni
- mitochondrial transport Source: Ensembl
- modulation of age-related behavioral decline Source: ARUK-UCLInferred from genetic interactioni
- myeloid dendritic cell differentiation Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKBInferred from direct assayi
- negative regulation of apoptotic signaling pathway Source: Ensembl
- negative regulation of axonogenesis Source: Ensembl
- negative regulation of core promoter binding Source: CAFAInferred from mutant phenotypei
- negative regulation of epidermal growth factor-activated receptor activity Source: Ensembl
- negative regulation of neuron apoptotic process Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: CAFAInferred from mutant phenotypei
- negative regulation of ubiquitin-dependent protein catabolic process Source: Ensembl
- negative regulation of ubiquitin-protein transferase activity Source: Ensembl
- neural retina development Source: Ensembl
- neuron apoptotic process Source: Ensembl
- neuron development Source: Ensembl
- neuron migration Source: Ensembl
- neuron projection maintenance Source: ARUK-UCLInferred from genetic interactioni
- neutrophil degranulation Source: Reactome
- Notch receptor processing Source: HGNCTraceable author statementi
- Notch receptor processing, ligand-dependent Source: Reactome
- positive regulation of amyloid fibril formation Source: ARUK-UCLInferred from genetic interactioni
- positive regulation of apoptotic process Source: Ensembl
- positive regulation of catalytic activity Source: HGNCInferred from direct assayi
- positive regulation of coagulation Source: Ensembl
- positive regulation of dendritic spine development Source: CACAOInferred from mutant phenotypei
- positive regulation of L-glutamate import across plasma membrane Source: Ensembl
- positive regulation of phosphorylation Source: ARUK-UCLInferred from genetic interactioni
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
- positive regulation of protein binding Source: ARUK-UCLInferred from genetic interactioni
- positive regulation of protein import into nucleus Source: UniProtKBInferred from mutant phenotypei
- positive regulation of receptor recycling Source: Ensembl
- positive regulation of transcription, DNA-templated Source: CACAOInferred from mutant phenotypei
- post-embryonic development Source: Ensembl
- protein glycosylation Source: Ensembl
- protein processing Source: HGNCInferred from direct assayi
- protein transport Source: Ensembl
- regulation of canonical Wnt signaling pathway Source: UniProtKB
- regulation of neuron projection development Source: UniProtKBInferred from mutant phenotypei
- regulation of phosphorylation Source: UniProtKBInferred from direct assayi
- regulation of resting membrane potential Source: Ensembl
- regulation of synaptic plasticity Source: Ensembl
- regulation of synaptic transmission, glutamatergic Source: Ensembl
- response to oxidative stress Source: Ensembl
- skeletal system morphogenesis Source: Ensembl
- skin morphogenesis Source: Ensembl
- smooth endoplasmic reticulum calcium ion homeostasis Source: GO_CentralInferred from biological aspect of ancestori
- somitogenesis Source: Ensembl
- synapse organization Source: ARUK-UCLInferred from genetic interactioni
- synaptic vesicle targeting Source: Ensembl
- T cell activation involved in immune response Source: Ensembl
- T cell receptor signaling pathway Source: Ensembl
- thymus development Source: Ensembl
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Molecular function | Hydrolase, Protease |
| Biological process | Apoptosis, Cell adhesion, Notch signaling pathway |
Enzyme and pathway databases
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-1251985 Nuclear signaling by ERBB4 R-HSA-1474228 Degradation of the extracellular matrix R-HSA-193692 Regulated proteolysis of p75NTR R-HSA-205043 NRIF signals cell death from the nucleus R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus R-HSA-3928665 EPH-ephrin mediated repulsion of cells R-HSA-6798695 Neutrophil degranulation R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus R-HSA-9017802 Noncanonical activation of NOTCH3 |
SignaLink: a signaling pathway resource with multi-layered regulatory networks More...SignaLinki | P49768 |
SIGNOR Signaling Network Open Resource More...SIGNORi | P49768 |
Protein family/group databases
MEROPS protease database More...MEROPSi | A22.001 |
Transport Classification Database More...TCDBi | 1.A.54.1.1 the presenilin er ca(2+) leak channel (presenilin) family |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Presenilin-1 (EC:3.4.23.-6 PublicationsManual assertion based on experiment ini
Short name: PS-1 Alternative name(s): Protein S182 Cleaved into the following 3 chains: |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:PSEN1 Synonyms:AD3, PS1, PSNL1 |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Eukaryotic Pathogen Database Resources More...EuPathDBi | HostDB:ENSG00000080815.18 |
Human Gene Nomenclature Database More...HGNCi | HGNC:9508 PSEN1 |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 104311 gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_P49768 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Plasma membrane
- Cell membrane 4 Publications
Manual assertion based on experiment ini
- Ref.21"Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch."
Ray W.J., Yao M., Mumm J., Schroeter E.H., Saftig P., Wolfe M., Selkoe D.J., Kopan R., Goate A.M.
J. Biol. Chem. 274:36801-36807(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH. - Ref.26"Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules."
Mirinics Z.K., Calafat J., Udby L., Lovelock J., Kjeldsen L., Rothermund K., Sisodia S.S., Borregaard N., Corey S.J.
Blood Cells Mol. Dis. 28:28-38(2002) [PubMed] [Europe PMC] [Abstract]Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION. - Ref.27"A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions."
Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T., Robakis N.K.
EMBO J. 21:1948-1956(2002) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH CDH1 AND CTNNB1. - Ref.50"Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation."
Viswanathan J., Haapasalo A., Bottcher C., Miettinen R., Kurkinen K.M., Lu A., Thomas A., Maynard C.J., Romano D., Hyman B.T., Berezovska O., Bertram L., Soininen H., Dantuma N.P., Tanzi R.E., Hiltunen M.
Traffic 12:330-348(2011) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH UBQLN1.
Manual assertion based on experiment ini
- Ref.55"Sampling the conformational space of the catalytic subunit of human gamma-secretase."
Bai X.C., Rajendra E., Yang G., Shi Y., Scheres S.H.
Elife 4:0-0(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS), SUBUNIT, TOPOLOGY. - Ref.57"Structural basis of human gamma-secretase assembly."
Sun L., Zhao L., Yang G., Yan C., Zhou R., Zhou X., Xie T., Zhao Y., Wu S., Li X., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 112:6003-6008(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 81-463, SUBUNIT, TOPOLOGY.
- Cell membrane 4 Publications
Endosome
- Early endosome 1 Publication
Manual assertion based on experiment ini
- Ref.52"G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH APH1 AND PEN2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT AD3 ASP-206.
- Early endosome membrane 1 Publication
Manual assertion inferred by curator fromi
- Ref.52"G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH APH1 AND PEN2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT AD3 ASP-206.
Manual assertion based on experiment ini
- Ref.55"Sampling the conformational space of the catalytic subunit of human gamma-secretase."
Bai X.C., Rajendra E., Yang G., Shi Y., Scheres S.H.
Elife 4:0-0(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS), SUBUNIT, TOPOLOGY. - Ref.57"Structural basis of human gamma-secretase assembly."
Sun L., Zhao L., Yang G., Yan C., Zhou R., Zhou X., Xie T., Zhao Y., Wu S., Li X., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 112:6003-6008(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 81-463, SUBUNIT, TOPOLOGY.
- Early endosome 1 Publication
Golgi apparatus
- Golgi apparatus membrane 2 Publications
Manual assertion inferred by curator fromi
- Ref.12"Purification and characterization of the human gamma-secretase complex."
Fraering P.C., Ye W., Strub J.-M., Dolios G., LaVoie M.J., Ostaszewski B.L., van Dorsselaer A., Wang R., Selkoe D.J., Wolfe M.S.
Biochemistry 43:9774-9789(2004) [PubMed] [Europe PMC] [Abstract] - Ref.22"Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin."
Levesque G., Yu G., Nishimura M., Zhang D.M., Levesque L., Yu H., Xu D., Liang Y., Rogaeva E.A., Ikeda M., Duthie M., Murgolo N., Wang L., VanderVere P., Bayne M.L., Strader C.D., Rommens J.M., Fraser P.E., St George-Hyslop P.H.
J. Neurochem. 72:999-1008(1999) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH CTNND2 AND CTNNB1, SUBCELLULAR LOCATION.
Manual assertion based on experiment ini
- Ref.13"Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells."
Kovacs D.M., Fausett H.J., Page K.J., Kim T.-W., Moir R.D., Merriam D.E., Hollister R.D., Hallmark O.G., Mancini R., Felsenstein K.M., Hyman B.T., Tanzi R.E., Wasco W.
Nat. Med. 2:224-229(1996) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY. - Ref.21"Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch."
Ray W.J., Yao M., Mumm J., Schroeter E.H., Saftig P., Wolfe M., Selkoe D.J., Kopan R., Goate A.M.
J. Biol. Chem. 274:36801-36807(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH.
Manual assertion based on experiment ini
- Ref.54"Three-dimensional structure of human gamma-secretase."
Lu P., Bai X.C., Ma D., Xie T., Yan C., Sun L., Yang G., Zhao Y., Zhou R., Scheres S.H., Shi Y.
Nature 512:166-170(2014) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.5 ANGSTROMS), FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY. - Ref.55"Sampling the conformational space of the catalytic subunit of human gamma-secretase."
Bai X.C., Rajendra E., Yang G., Shi Y., Scheres S.H.
Elife 4:0-0(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS), SUBUNIT, TOPOLOGY. - Ref.56"An atomic structure of human gamma-secretase."
Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., Shi Y.
Nature 525:212-217(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS AD3 LEU-213; ILE-237 AND PHE-261, MUTAGENESIS OF ILE-202; LEU-226; LEU-248 AND LEU-424. - Ref.57"Structural basis of human gamma-secretase assembly."
Sun L., Zhao L., Yang G., Yan C., Zhou R., Zhou X., Xie T., Zhao Y., Wu S., Li X., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 112:6003-6008(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 81-463, SUBUNIT, TOPOLOGY.
- Golgi apparatus membrane 2 Publications
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Manual assertion based on experiment ini
- Ref.52"G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH APH1 AND PEN2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT AD3 ASP-206.
- Endoplasmic reticulum membrane 2 Publications
Manual assertion inferred by curator fromi
- Ref.12"Purification and characterization of the human gamma-secretase complex."
Fraering P.C., Ye W., Strub J.-M., Dolios G., LaVoie M.J., Ostaszewski B.L., van Dorsselaer A., Wang R., Selkoe D.J., Wolfe M.S.
Biochemistry 43:9774-9789(2004) [PubMed] [Europe PMC] [Abstract] - Ref.22"Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin."
Levesque G., Yu G., Nishimura M., Zhang D.M., Levesque L., Yu H., Xu D., Liang Y., Rogaeva E.A., Ikeda M., Duthie M., Murgolo N., Wang L., VanderVere P., Bayne M.L., Strader C.D., Rommens J.M., Fraser P.E., St George-Hyslop P.H.
J. Neurochem. 72:999-1008(1999) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH CTNND2 AND CTNNB1, SUBCELLULAR LOCATION.
Manual assertion based on experiment ini
- Ref.13"Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells."
Kovacs D.M., Fausett H.J., Page K.J., Kim T.-W., Moir R.D., Merriam D.E., Hollister R.D., Hallmark O.G., Mancini R., Felsenstein K.M., Hyman B.T., Tanzi R.E., Wasco W.
Nat. Med. 2:224-229(1996) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY. - Ref.17"Direct association of presenilin-1 with beta-catenin."
Murayama M., Tanaka S., Palacino J., Murayama O., Honda T., Sun X., Yasutake K., Nihonmatsu N., Wolozin B., Takashima A.
FEBS Lett. 433:73-77(1998) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CTNNB1, SUBCELLULAR LOCATION. - Ref.21"Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch."
Ray W.J., Yao M., Mumm J., Schroeter E.H., Saftig P., Wolfe M., Selkoe D.J., Kopan R., Goate A.M.
J. Biol. Chem. 274:36801-36807(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH.
Manual assertion based on experiment ini
- Ref.54"Three-dimensional structure of human gamma-secretase."
Lu P., Bai X.C., Ma D., Xie T., Yan C., Sun L., Yang G., Zhao Y., Zhou R., Scheres S.H., Shi Y.
Nature 512:166-170(2014) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.5 ANGSTROMS), FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY. - Ref.55"Sampling the conformational space of the catalytic subunit of human gamma-secretase."
Bai X.C., Rajendra E., Yang G., Shi Y., Scheres S.H.
Elife 4:0-0(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS), SUBUNIT, TOPOLOGY. - Ref.56"An atomic structure of human gamma-secretase."
Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., Shi Y.
Nature 525:212-217(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS AD3 LEU-213; ILE-237 AND PHE-261, MUTAGENESIS OF ILE-202; LEU-226; LEU-248 AND LEU-424. - Ref.57"Structural basis of human gamma-secretase assembly."
Sun L., Zhao L., Yang G., Yan C., Zhou R., Zhou X., Xie T., Zhao Y., Wu S., Li X., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 112:6003-6008(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 81-463, SUBUNIT, TOPOLOGY.
- Endoplasmic reticulum 1 Publication
Other locations
- Cytoplasmic granule 1 Publication
Manual assertion based on experiment ini
- Ref.26"Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules."
Mirinics Z.K., Calafat J., Udby L., Lovelock J., Kjeldsen L., Rothermund K., Sisodia S.S., Borregaard N., Corey S.J.
Blood Cells Mol. Dis. 28:28-38(2002) [PubMed] [Europe PMC] [Abstract]Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
- growth cone 1 Publication
Manual assertion based on experiment ini
- Ref.34"A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations."
Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.
J. Alzheimers Dis. 6:31-43(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT AD3 SER-117, CHARACTERIZATION OF VARIANTS AD3 LEU-117 AND SER-117.
Note: Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface (PubMed:10593990). Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane (PubMed:9738936). Also present in azurophil granules of neutrophils (PubMed:11987239). Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes (PubMed:21143716). Localizes to neurites (PubMed:15004326).5 Publications- Cytoplasmic granule 1 Publication
- Ref.17"Direct association of presenilin-1 with beta-catenin."
Murayama M., Tanaka S., Palacino J., Murayama O., Honda T., Sun X., Yasutake K., Nihonmatsu N., Wolozin B., Takashima A.
FEBS Lett. 433:73-77(1998) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CTNNB1, SUBCELLULAR LOCATION. - Ref.21"Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch."
Ray W.J., Yao M., Mumm J., Schroeter E.H., Saftig P., Wolfe M., Selkoe D.J., Kopan R., Goate A.M.
J. Biol. Chem. 274:36801-36807(1999) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NOTCH. - Ref.26"Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules."
Mirinics Z.K., Calafat J., Udby L., Lovelock J., Kjeldsen L., Rothermund K., Sisodia S.S., Borregaard N., Corey S.J.
Blood Cells Mol. Dis. 28:28-38(2002) [PubMed] [Europe PMC] [Abstract]Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION. - Ref.34"A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations."
Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.
J. Alzheimers Dis. 6:31-43(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT AD3 SER-117, CHARACTERIZATION OF VARIANTS AD3 LEU-117 AND SER-117. - Ref.50"Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation."
Viswanathan J., Haapasalo A., Bottcher C., Miettinen R., Kurkinen K.M., Lu A., Thomas A., Maynard C.J., Romano D., Hyman B.T., Berezovska O., Bertram L., Soininen H., Dantuma N.P., Tanzi R.E., Hiltunen M.
Traffic 12:330-348(2011) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH UBQLN1.
Manual assertion based on experiment ini
Cytoskeleton
- centrosome Source: UniProtKBInferred from direct assayi
- ciliary rootlet Source: Ensembl
Endoplasmic reticulum
- endoplasmic reticulum Source: HGNCInferred from direct assayi
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
- rough endoplasmic reticulum Source: UniProtKBInferred from direct assayi
- smooth endoplasmic reticulum Source: UniProtKBInferred from direct assayi
Endosome
- early endosome Source: Ensembl
Golgi apparatus
- Golgi apparatus Source: UniProtKBInferred from direct assayi
- Golgi membrane Source: UniProtKB-SubCell
Lysosome
- azurophil granule membrane Source: Reactome
Mitochondrion
- mitochondrial inner membrane Source: Ensembl
- mitochondrion Source: UniProtKBInferred from direct assayi
Nucleus
- nuclear membrane Source: UniProtKBInferred from direct assayi
- nuclear outer membrane Source: MGIInferred from direct assayi
- nucleus Source: HPA
Plasma Membrane
- gamma-secretase complex Source: UniProtKBInferred from direct assayi
- integral component of plasma membrane Source: HGNCInferred from direct assayi
- integral component of presynaptic membrane Source: Ensembl
- plasma membrane Source: UniProtKBInferred from direct assayi
- sarcolemma Source: Ensembl
Other locations
- aggresome Source: UniProtKBInferred from direct assayi
- cell cortex Source: Ensembl
- cell junction Source: HPA
- cell surface Source: Ensembl
- dendritic shaft Source: Ensembl
- growth cone Source: UniProtKBInferred from direct assayi
- integral component of membrane Source: UniProtKBInferred from direct assayi
- kinetochore Source: UniProtKBInferred from direct assayi
- membrane Source: MGIInferred from direct assayi
- membrane raft Source: UniProtKBInferred from direct assayi
- neuromuscular junction Source: Ensembl
- neuron projection Source: UniProtKBInferred from direct assayi
- neuronal cell body Source: Ensembl
- protein-containing complex Source: CAFAInferred from mutant phenotypei
- synaptic vesicle Source: Ensembl
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini | 1 – 82 | Cytoplasmic1 Publication Manual assertion based on experiment ini
| 82 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei | 83 – 103 | Helical1 Publication Manual assertion based on experiment ini
| 21 | |
| Topological domaini | 104 – 132 | Lumenal1 Publication Manual assertion based on experiment ini
| 29 | |
| Transmembranei | 133 – 153 | Helical1 Publication Manual assertion based on experiment ini
| 21 | |
| Topological domaini | 154 – 166 | Cytoplasmic1 Publication Manual assertion based on experiment ini
| 13 | |
| Transmembranei | 167 – 189 | Helical1 Publication Manual assertion based on experiment ini
| 23 | |
| Topological domaini | 190 – 194 | Lumenal1 Publication Manual assertion based on experiment ini
| 5 | |
| Transmembranei | 195 – 216 | Helical1 Publication Manual assertion based on experiment ini
| 22 | |
| Topological domaini | 217 – 220 | Cytoplasmic1 Publication Manual assertion based on experiment ini
| 4 | |
| Transmembranei | 221 – 241 | Helical1 Publication Manual assertion based on experiment ini
| 21 | |
| Topological domaini | 242 – 248 | Lumenal1 Publication Manual assertion based on experiment ini
| 7 | |
| Transmembranei | 249 – 272 | Helical1 Publication Manual assertion based on experiment ini
| 24 | |
| Topological domaini | 273 – 380 | Cytoplasmic1 Publication Manual assertion based on experiment ini
| 108 | |
| Transmembranei | 381 – 401 | Helical1 Publication Manual assertion based on experiment ini
| 21 | |
| Topological domaini | 402 – 407 | Lumenal1 Publication Manual assertion based on experiment ini
| 6 | |
| Transmembranei | 408 – 428 | Helical1 Publication Manual assertion based on experiment ini
| 21 | |
| Topological domaini | 429 – 432 | Cytoplasmic1 Publication Manual assertion based on experiment ini
| 4 | |
| Transmembranei | 433 – 453 | Helical1 Publication Manual assertion based on experiment ini
| 21 | |
| Topological domaini | 454 – 467 | Lumenal1 Publication Manual assertion based on experiment ini
| 14 |
Keywords - Cellular componenti
Cell membrane, Cell projection, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Alzheimer disease 3 (AD3)82 PublicationsManual assertion based on experiment ini
- Ref.1"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease."
Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. , Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 375:754-760(1995) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS AD3 LEU-146; ARG-163; GLU-246 AND VAL-286, TISSUE SPECIFICITY. - Ref.29"A new splice variant of glial fibrillary acidic protein GFAPepsilon, interacts with the presenilin proteins."
Nielsen A.L., Holm I.E., Johansen M., Bonven B., Jorgensen P., Jorgensen A.L.
J. Biol. Chem. 277:29983-29991(2002) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH GFAP, MUTAGENESIS OF 66-ASP--ASP-72; 76-LYS-TYR-77; 82-VAL-ILE-83; VAL-82 AND 84-MET-LEU-85, CHARACTERIZATION OF VARIANTS AD3 VAL-79 AND LEU-82. - Ref.34"A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations."
Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.
J. Alzheimers Dis. 6:31-43(2004) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT AD3 SER-117, CHARACTERIZATION OF VARIANTS AD3 LEU-117 AND SER-117. - Ref.40"Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations."
Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., Serneels L., De Strooper B., Yu G., Bezprozvanny I.
Cell 126:981-993(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANT AD3 VAL-146. - Ref.41"C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation."
Wang J., Beher D., Nyborg A.C., Shearman M.S., Golde T.E., Goate A.
J. Neurochem. 96:218-227(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION OF PAL MOTIF, MUTAGENESIS OF PRO-433; ALA-434 AND LEU-435, CHARACTERIZATION OF VARIANT AD3 PHE-435. - Ref.52"G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH APH1 AND PEN2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT AD3 ASP-206. - Ref.56"An atomic structure of human gamma-secretase."
Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., Shi Y.
Nature 525:212-217(2015) [PubMed] [Europe PMC] [Abstract]Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS AD3 LEU-213; ILE-237 AND PHE-261, MUTAGENESIS OF ILE-202; LEU-226; LEU-248 AND LEU-424. - Ref.58"Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3."
Cruts M., Backhovens H., Wang S.-Y., van Gassen G., Theuns J., de Jonghe C., Wehnert A., de Voecht J., de Winter G., Cras P., Bruyland M., Datson N., Weissenbach J., den Dunnen J.T., Martin J.-J., Hendriks L., Van Broeckhoven C.
Hum. Mol. Genet. 4:2363-2372(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 THR-143 AND ALA-384. - Ref.59"Mutations of the presenilin I gene in families with early-onset Alzheimer's disease."
Campion D., Flaman J.-M., Brice A., Hannequin D., Dubois B., Martin C., Moreau V., Charbonnier F., Didierjean O., Tardieu S., Penet C., Puel M., Pasquier F., le Doze F., Bellis G., Calenda A., Heilig R., Martinez M. , Mallet J., Bellis M., Clerget-Darpoux F., Agid Y., Frebourg T.
Hum. Mol. Genet. 4:2373-2377(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 LEU-82; HIS-115; THR-139; ARG-163; THR-231; LEU-264; VAL-392 AND TYR-410. - Ref.60"Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene."
Rogaev E.I., Sherrington R., Rogaeva E.A., Levesque G., Ikeda M., Liang Y., Chi H., Lin C., Holman K., Tsuda T., Mar L., Sorbi S., Nacmias B., Piacentini S., Amaducci L., Chumakov I., Cohen D., Lannfelt L. , Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 376:775-778(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 VAL-260; VAL-285 AND VAL-392. - Ref.61"The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families."
Clark R.F., Hutton M., Fuldner R.A., Froelich S., Karran E., Talbot C., Crook R., Lendon C.L., Prihar G., He C., Korenblat K., Martinez A., Wragg M., Busfield F., Behrens M.I., Myers A., Norton J., Morris J. , Mehta N., Pearson C., Lincoln S., Baker M., Duff K., Zehr C., Perez-Tur J., Houlden H., Ruiz A., Ossa J., Lopera F., Arcos M., Madrigal L., Collinge J., Humphreys C., Asworth T., Sarner S., Fox N.C., Harvey R., Kennedy A., Roques P.K., Cline R.T., Phillips C.A., Venter J.C., Forsel L., Axelman K., Lilius L., Johnston J., Cowburn R., Viitanen M., Winblad B., Kosik K.S., Haltia M., Poyhonen M., Dickson D., Mann D., Neary D., Snowden J., Lantos P., Lannfelt L., Rossor M.N., Roberts G.W., Adams M.D., Hardy J., Goate A.M.
Nat. Genet. 11:219-222(1995) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 VAL-139; VAL-146; TYR-163; THR-267; ALA-280 AND GLY-280. - Ref.62"The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology."
Lemere C.A., Lopera F., Kosik K.S., Lendon C.L., Ossa J., Saido T.C., Yamaguchi H., Ruiz A., Martinez A., Madrigal L., Hincapie L., Arango J.C., Anthony D.C., Koo E.H., Goate A.M., Selkoe D.J., Arango J.C.
Nat. Med. 2:1146-1150(1996) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ALA-280, INVOLVEMENT IN AD3. - Ref.63"Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families."
Kamino K., Sato S., Sakaki Y., Yoshiiwa A., Nishiwaki Y., Takeda H., Tanabe H., Nishimura T., Li K., St George-Hyslop P.H., Miki T., Ogihara T.
Neurosci. Lett. 208:195-198(1996) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 PHE-96; ARG-163 AND THR-213. - Ref.64"Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation."
Crook R., Ellis R., Shanks M., Thal L.J., Perez-Tur J., Baker M., Hutton M., Haltia T., Hardy J., Galasko D.
Ann. Neurol. 42:124-128(1997) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ASP-135. - Ref.65"E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles."
Lendon C.L., Martinez A., Behrens I.M., Kosik K.S., Madrigal L., Norton J., Neuman R., Myers A., Busfield F., Wragg M., Arcos M., Arango-Viana J.C., Ossa J., Ruiz A., Goate A.M., Lopera F.
Hum. Mutat. 10:186-195(1997) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ALA-280. - Ref.66"Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype."
Kwok J.B.J., Taddei K., Hallupp M., Fisher C., Brooks W.S., Broe G.A., Hardy J., Fulham M.J., Nicholson G.A., Stell R., St George-Hyslop P.H., Fraser P.E., Kakulas B., Clarnette R., Relkin N., Gandy S.E., Schofield P.R., Martins R.N.
NeuroReport 8:1537-1542(1997) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 THR-233 AND THR-278. - Ref.67"A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease."
Ramirez-Duenas M.G., Rogaeva E.A., Leal C.A., Lin C., Ramirez-Casillas G.A., Hernandez-Romo J.A., St George-Hyslop P.H., Cantu J.M.
Ann. Genet. 41:149-153(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PRO-171. - Ref.70"Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease."
Cruts M., van Duijn C.M., Backhovens H., van den Broeck M., Wehnert A., Serneels S., Sherrington R., Hutton M., Hardy J., St George-Hyslop P.H., Hofman A., van Broeckhoven C.
Hum. Mol. Genet. 7:43-51(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 VAL-79; CYS-115 AND VAL-231, VARIANT GLY-318. - Ref.71"Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene."
Poorkaj P., Sharma V., Anderson L., Nemens E., Alonso M.E., Orr H., White J., Heston L., Bird T.D., Schellenberg G.D.
Hum. Mutat. 11:216-221(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 ASP-120; ARG-163; VAL-209; VAL-260; LEU-264; TYR-410 AND PRO-426. - Ref.72"Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification."
Besancon R., Lorenzi A., Cruts M., Radawiec S., Sturtz F., Broussolle E., Chazot G., van Broeckhoven C., Chamba G., Vandenberghe A.
Hum. Mutat. 11:481-481(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 GLU-378. - Ref.73"De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases."
Dumanchin C., Brice A., Campion D., Hannequin D., Martin C., Moreau V., Agid Y., Martinez M., Clerget-Darpoux F., Frebourg T.
J. Med. Genet. 35:672-673(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 LYS-139. - Ref.74"A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years."
Wisniewski T., Dowjat W.K., Buxbaum J.D., Khorkova O., Efthimiopoulos S., Kulczycki J., Lojkowska W., Wegiel J., Wisniewski H.M., Frangione B.
NeuroReport 9:217-221(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 LEU-117. - Ref.75"Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease."
Taddei K., Kwok J.B., Kril J.J., Halliday G.M., Creasey H., Hallupp M., Fisher C., Brooks W.S., Chung C., Andrews C., Masters C.L., Schofield P.R., Martins R.N.
NeuroReport 9:3335-3339(1998) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 LEU-169 AND GLN-436. - Ref.77"Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum."
Campion D., Dumanchin C., Hannequin D., Dubois B., Belliard S., Puel M., Thomas-Anterion C., Michon A., Martin C., Charbonnier F., Raux G., Camuzat A., Penet C., Mesnage V., Martinez M., Clerget-Darpoux F., Brice A., Frebourg T.
Am. J. Hum. Genet. 65:664-670(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 LEU-82; HIS-115; ASP-120; THR-139; LEU-146; ILE-147; ARG-163; CYS-165; TRP-173; THR-231; THR-233; PRO-235; LEU-264; ILE-390; VAL-392 AND TYR-410, VARIANT GLY-318. - Ref.78"Pathogenic presenilin 1 mutations (P436S and I143F) in early-onset Alzheimer's disease in the UK."
Palmer M.S., Beck J.A., Campbell T.A., Humphries C.B., Roques P.K., Fox N.C., Harvey R., Rossor M.N., Collinge J.
Hum. Mutat. 13:256-256(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 PHE-143 AND SER-436. - Ref.79"A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease."
Sugiyama N., Suzuki K., Matsumura T., Kawanishi C., Onishi H., Yamada Y., Iseki E., Kosaka K.
Hum. Mutat. 14:90-90(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ARG-209. - Ref.80"DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations."
Aldudo J., Bullido M.J., Valdivieso F.
Hum. Mutat. 14:433-439(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 LEU-233; ARG-282 AND THR-409, VARIANT GLY-318. - Ref.81"A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures."
Ezquerra M., Carnero C., Blesa R., Gelpi J.L., Ballesta F., Oliva R.
Neurology 52:566-570(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PRO-169. - Ref.82"Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene."
Smith M.J., Gardner R.J., Knight M.A., Forrest S.M., Beyreuther K., Storey E., McLean C.A., Cotton R.G., Cappal R., Masters C.L.
NeuroReport 10:503-507(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PRO-219. - Ref.83"A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease."
Romero I., Joergensen P., Bolwig G., Fraser P.E., Rogaeva E., Mann D., Havsager A.-M., Joergensen A.L.
NeuroReport 10:2255-2260(1999) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ASN-116. - Ref.84"High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes."
Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.
Am. J. Hum. Genet. 66:110-117(2000) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 VAL-79; LEU-105 AND VAL-139, VARIANT GLY-318. - Ref.85"Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy."
Yasuda M., Maeda S., Kawamata T., Tamaoka A., Yamamoto Y., Kuroda S., Maeda K., Tanaka C.
J. Neurol. Neurosurg. Psych. 68:220-223(2000) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 SER-405. - Ref.86"The presenilin 1 C92S mutation increases abeta 42 production."
Lewis P.A., Perez-Tur J., Golde T.E., Hardy J.
Biochem. Biophys. Res. Commun. 277:261-263(2000) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 SER-92. - Ref.88"Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia."
Arango D., Cruts M., Torres O., Backhovens H., Serrano M.L., Villareal E., Montanes P., Matallana D., Cano C., Van Broeckhoven C., Jacquier M.
Am. J. Med. Genet. 103:138-143(2001) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 MET-94; THR-143 AND ALA-280, VARIANT GLY-318. - Ref.89"Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation."
Dermaut B., Kumar-Singh S., De Jonghe C., Cruts M., Loefgren A., Luebke U., Cras P., Dom R., De Deyn P.P., Martin J.J., Van Broeckhoven C.
Brain 124:2383-2392(2001) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 VAL-282, CHARACTERIZATION OF VARIANT AD3 VAL-282. - Ref.90Cited for: VARIANT AD3 GLU-431.
- Ref.91"A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families."
Athan E.S., Williamson J., Ciappa A., Santana V., Romas S.N., Lee J.H., Rondon H., Lantigua R.A., Medrano M., Torres M., Arawaka S., Rogaeva E., Song Y.-Q., Sato C., Kawarai T., Fafel K.C., Boss M.A., Seltzer W.K. , Stern Y., St George-Hyslop P.H., Tycko B., Mayeux R.
JAMA 286:2257-2263(2001) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ALA-206. - Ref.92"Very early onset Alzheimer's disease with spastic paraparesis associated with a novel presenilin 1 mutation (Phe237Ile)."
Sodeyama N., Iwata T., Ishikawa K., Mizusawa H., Yamada M., Itoh Y., Otomo E., Matsushita M., Komatsuzaki Y.
J. Neurol. Neurosurg. Psych. 71:556-557(2001) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ILE-237. - Ref.93"Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations."
Rogaeva E.A., Fafel K.C., Song Y.Q., Medeiros H., Sato C., Liang Y., Richard E., Rogaev E.I., Frommelt P., Sadovnick A.D., Meschino W., Rockwood K., Boss M.A., Mayeux R., St George-Hyslop P.
Neurology 57:621-625(2001) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 GLN-35; VAL-79; CYS-115; ASN-116; THR-143; ILE-146; LEU-146; VAL-146; TYR-156 DELINS PHE-THR-TYR; ARG-163; LEU-177; SER-177; PRO-178; ALA-206; SER-206; GLU-209; LEU-213; ARG-222; THR-231; LEU-233; PRO-235; PHE-261; ARG-274; ARG-352 INS; ILE-354; GLN-358; TYR-365; VAL-394; PHE-418; GLU-431; PHE-435 AND VAL-439, VARIANT GLY-318. - Ref.94"Molecular evidence of presenilin 1 mutation in familial early onset dementia."
Matsubara-Tsutsui M., Yasuda M., Yamagata H., Nomura T., Taguchi K., Kohara K., Miyoshi K., Miki T.
Am. J. Med. Genet. 114:292-298(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 SER-266. - Ref.95"A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances."
Queralt R., Ezquerra M., Lleo A., Castellvi M., Gelpi J., Ferrer I., Acarin N., Pasarin L., Blesa R., Oliva R.
J. Neurol. Neurosurg. Psych. 72:266-269(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 LEU-89. - Ref.96"Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities."
O'Riordan S., McMonagle P., Janssen J.C., Fox N.C., Farrell M., Collinge J., Rossor M.N., Hutchinson M.
Neurology 59:1108-1110(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 GLY-280. - Ref.97"Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production."
Moehlmann T., Winkler E., Xia X., Edbauer D., Murrell J., Capell A., Kaether C., Zheng H., Ghetti B., Haass C., Steiner H.
Proc. Natl. Acad. Sci. U.S.A. 99:8025-8030(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PRO-166. - Ref.98"A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease."
Bertoli-Avella A.M., Marcheco Teruel B., Llibre Rodriguez J.J., Gomez Viera N., Borrajero-Martinez I., Severijnen E.A., Joosse M., van Duijn C.M., Heredero Baute L., Heutink P.
Neurogenetics 4:97-104(2002) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 MET-174. - Ref.99"Presenilin-1 mutation L271V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy."
Kwok J.B.J., Halliday G.M., Brooks W.S., Dolios G., Laudon H., Murayama O., Hallupp M., Badenhop R.F., Vickers J., Wang R., Naslund J., Takashima A., Gandy S.E., Schofield P.R.
J. Biol. Chem. 278:6748-6754(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 VAL-271. - Ref.100"Early onset familial Alzheimer's disease: Mutation frequency in 31 families."
Janssen J.C., Beck J.A., Campbell T.A., Dickinson A., Fox N.C., Harvey R.J., Houlden H., Rossor M.N., Collinge J.
Neurology 60:235-239(2003) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 CYS-115; ILE-146; VAL-153; CYS-154; ILE-168 DEL; PRO-171; ASP-184; PHE-229; VAL-235; LEU-237; VAL-260; PHE-263; HIS-269; MET-377 AND VAL-378, VARIANT GLY-318. - Ref.101"A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques."
Dermaut B., Kumar-Singh S., Engelborghs S., Theuns J., Rademakers R., Saerens J., Pickut B.A., Peeters K., van den Broeck M., Vennekens K., Claes S., Cruts M., Cras P., Martin J.J., Van Broeckhoven C., De Deyn P.P.
Ann. Neurol. 55:617-626(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PIDB VAL-183, CHARACTERIZATION OF VARIANTS AD3 THR-143 AND VAL-282, CHARACTERIZATION OF VARIANT PIDB VAL-183. - Ref.102"A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis."
Ataka S., Tomiyama T., Takuma H., Yamashita T., Shimada H., Tsutada T., Kawabata K., Mori H., Miki T.
Arch. Neurol. 61:1773-1776(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PRO-85, CHARACTERIZATION OF VARIANT AD3 PRO-85. - Ref.103"A presenilin 1 R278I mutation presenting with language impairment."
Godbolt A.K., Beck J.A., Collinge J., Garrard P., Warren J.D., Fox N.C., Rossor M.N.
Neurology 63:1702-1704(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ILE-278. - Ref.104"A novel presenilin 1 mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis."
Hattori S., Sakuma K., Wakutani Y., Wada K., Shimoda M., Urakami K., Kowa H., Nakashima K.
Neurosci. Lett. 368:319-322(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ASN-154. - Ref.105"Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life."
Snider B.J., Norton J., Coats M.A., Chakraverty S., Hou C.E., Jervis R., Lendon C.L., Goate A.M., McKeel D.W. Jr., Morris J.C.
Arch. Neurol. 62:1821-1830(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-170. - Ref.108"Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40."
Kumar-Singh S., Theuns J., Van Broeck B., Pirici D., Vennekens K., Corsmit E., Cruts M., Dermaut B., Wang R., Van Broeckhoven C.
Hum. Mutat. 27:686-695(2006) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 VAL-79; THR-143; VAL-231; PHE-262; PHE-263; VAL-282 AND ALA-384. - Ref.109"Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer's disease in Mexican families."
Yescas P., Huertas-Vazquez A., Villarreal-Molina M.T., Rasmussen A., Tusie-Luna M.T., Lopez M., Canizales-Quinteros S., Alonso M.E.
Neurogenetics 7:195-200(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 GLU-431. - Ref.110"The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families."
Murrell J., Ghetti B., Cochran E., Macias-Islas M.A., Medina L., Varpetian A., Cummings J.L., Mendez M.F., Kawas C., Chui H., Ringman J.M.
Neurogenetics 7:277-279(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 GLU-431. - Ref.111"Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation."
Kauwe J.S., Jacquart S., Chakraverty S., Wang J., Mayo K., Fagan A.M., Holtzman D.M., Morris J.C., Goate A.M.
Ann. Neurol. 61:446-453(2007) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 VAL-79, CHARACTERIZATION OF VARIANT AD3 VAL-79. - Ref.112"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype."
Piccini A., Zanusso G., Borghi R., Noviello C., Monaco S., Russo R., Damonte G., Armirotti A., Gelati M., Giordano R., Zambenedetti P., Russo C., Ghetti B., Tabaton M.
Arch. Neurol. 64:738-745(2007) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-170. - Ref.113"Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor."
Litterst C., Georgakopoulos A., Shioi J., Ghersi E., Wisniewski T., Wang R., Ludwig A., Robakis N.K.
J. Biol. Chem. 282:16155-16163(2007) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 LEU-117; LEU-146; GLU-246; VAL-260; LEU-264 AND GLY-280, FUNCTION, MUTAGENESIS OF ASP-257. - Ref.115"Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta."
Shimojo M., Sahara N., Mizoroki T., Funamoto S., Morishima-Kawashima M., Kudo T., Takeda M., Ihara Y., Ichinose H., Takashima A.
J. Biol. Chem. 283:16488-16496(2008) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANT AD3 THR-213. - Ref.116"Novel PSEN1 mutation in a Bulgarian patient with very early-onset Alzheimer's disease, spastic paraparesis, and extrapyramidal signs."
Dintchov Traykov L., Mehrabian S., Van den Broeck M., Radoslavova Raycheva M., Cruts M., Kirilova Jordanova A., Van Broeckhoven C.
Am. J. Alzheimers Dis. Other Demen. 24:404-407(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 VAL-381. - Ref.117"Presenilin1 G217R mutation linked to Alzheimer disease with cotton wool plaques."
Norton J.B., Cairns N.J., Chakraverty S., Wang J., Levitch D., Galvin J.E., Goate A.
Neurology 73:480-482(2009) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ARG-217, CHARACTERIZATION OF VARIANT AD3 ARG-217. - Ref.118"Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation."
Bruni A.C., Bernardi L., Colao R., Rubino E., Smirne N., Frangipane F., Terni B., Curcio S.A., Mirabelli M., Clodomiro A., Di Lorenzo R., Maletta R., Anfossi M., Gallo M., Geracitano S., Tomaino C., Muraca M.G., Leotta A. , Lio S.G., Pinessi L., Rainero I., Sorbi S., Nee L., Milan G., Pappata S., Postiglione A., Abbamondi N., Forloni G., St George Hyslop P., Rogaeva E., Bugiani O., Giaccone G., Foncin J.F., Spillantini M.G., Puccio G.
Neurology 74:798-806(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 LEU-146. - Ref.119"A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity."
Heilig E.A., Xia W., Shen J., Kelleher R.J. III
J. Biol. Chem. 285:22350-22359(2010) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-435, CHARACTERIZATION OF VARIANTS AD3 PHE-435; GLN-436 AND SER-436, MUTAGENESIS OF PRO-433 AND LEU-435, FUNCTION. - Ref.120"Clinical phenotype of G206D mutation in the presenilin 1 gene in pathologically confirmed familial Alzheimer's disease."
Wu Y.Y., Cheng I.H., Lee C.C., Chiu M.J., Lee M.J., Chen T.F., Hsu J.L.
J. Alzheimers Dis. 25:145-150(2011) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ASP-206. - Ref.122"A novel PSEN1 gene mutation (L235R) associated with familial early-onset Alzheimer's disease."
Antonell A., Balasa M., Oliva R., Llado A., Bosch B., Fabregat N., Fortea J., Molinuevo J.L., Sanchez-Valle R.
Neurosci. Lett. 496:40-42(2011) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ARG-235. - Ref.123"Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of gamma-secretase."
Chau D.M., Crump C.J., Villa J.C., Scheinberg D.A., Li Y.M.
J. Biol. Chem. 287:17288-17296(2012) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 LEU-146; ARG-163 AND ALA-280. - Ref.124"Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients."
Lohmann E., Guerreiro R.J., Erginel-Unaltuna N., Gurunlian N., Bilgic B., Gurvit H., Hanagasi H.A., Luu N., Emre M., Singleton A.
Neurobiol. Aging 33:1850.E17-1850.E27(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 ARG-134; ARG-163 AND VAL-262, VARIANT TYR-214. - Ref.125"Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's disease."
Kerchner G.A., Holbrook K.
Neurosci. Lett. 531:142-144(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-159. - Ref.126"Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified gamma-secretase complexes."
Cacquevel M., Aeschbach L., Houacine J., Fraering P.C.
PLoS ONE 7:E35133-E35133(2012) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 PRO-166 AND GLN-436, MUTAGENESIS OF ASP-257 AND ASP-385. - Ref.127"Trans-dominant negative effects of pathogenic PSEN1 mutations on gamma-secretase activity and Abeta production."
Heilig E.A., Gutti U., Tai T., Shen J., Kelleher R.J. III
J. Neurosci. 33:11606-11617(2013) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 PRO-166; ILE-278; ALA-384; VAL-392; TYR-410 AND PHE-435. - Ref.128"A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease."
Dolzhanskaya N., Gonzalez M.A., Sperziani F., Stefl S., Messing J., Wen G.Y., Alexov E., Zuchner S., Velinov M.
J. Alzheimers Dis. 39:23-27(2014) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-381. - Ref.129"Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease."
Cornejo-Olivas M.R., Yu C.E., Mazzetti P., Mata I.F., Meza M., Lindo-Samanamud S., Leverenz J.B., Bird T.D.
Neurosci. Lett. 563:140-143(2014) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 VAL-153. - Ref.130"A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease."
Luedecke D., Becktepe J.S., Lehmbeck J.T., Finckh U., Yamamoto R., Jahn H., Boelmans K.
Neurosci. Lett. 566:115-119(2014) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 VAL-275. - Ref.131"Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease."
Achouri-Rassas A., Ben Ali N., Fray S., Hadj Fredj S., Kechaou M., Zakraoui N.O., Cherif A., Chabbi S., Anane N., Messaoud T., Gouider R., Belal S.
Neurobiol. Aging 36:2904.E09-2904.E11(2015) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 THR-83. - Ref.132"The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida."
Ravenscroft T.A., Pottier C., Murray M.E., Baker M., Christopher E., Levitch D., Brown P.H., Barker W., Duara R., Greig-Custo M., Betancourt A., English M., Sun X., Ertekin-Taner N., Graff-Radford N.R., Dickson D.W., Rademakers R.
Am. J. Neurodegener. Dis. 5:94-101(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 ALA-206 AND VAL-378. - Ref.133"Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease."
Tedde A., Bartoli A., Piaceri I., Ferrara S., Bagnoli S., Serio A., Sorbi S., Nacmias B.
Neurosci. Lett. 610:150-153(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 THR-408. - Ref.135"Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase."
Sun L., Zhou R., Yang G., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 114:E476-E485(2017) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS AD3 GLN-35; VAL-79; LEU-82; PRO-85; LEU-89; SER-92; MET-94; PHE-96; LEU-97; HIS-115; ASN-116; ASP-120; LYS-120; ARG-134; ASP-135; VAL-139; THR-143; LEU-146; ILE-147; VAL-153; ASN-154; ARG-163; TYR-163; PRO-166; PRO-169; PHE-170; PRO-171; TRP-173; MET-174; LEU-177; PRO-178; VAL-183; ASP-184; ALA-206; SER-206; ARG-209; VAL-209; LEU-213; ARG-217; ARG-222; PHE-229; THR-231; LEU-233; THR-233; ARG-235; PRO-235; VAL-235; ILE-237; GLU-246; SER-250; VAL-260; PHE-261; PHE-262; ARG-263; LEU-264; SER-266; SER-267; GLY-269; VAL-271; ARG-274; VAL-275; ALA-280; GLY-280; ARG-282; VAL-285; VAL-286; ILE-354; GLN-358; GLU-378; VAL-378; VAL-381; ALA-384; ILE-390; VAL-392; VAL-394; THR-396; SER-405; THR-409; TYR-410; PHE-418; PRO-426; GLU-431; PHE-435; SER-436 AND VAL-439, CHARACTERIZATION OF VARIANT CMD1U GLY-333, MUTAGENESIS OF THR-99; PHE-105; ARG-108; LEU-113; PRO-117; GLU-123; HIS-131; ALA-136; ILE-143; LEU-150; TRP-165; ILE-168; PHE-176; GLU-184; ILE-202; SER-212; HIS-214; LEU-219; GLN-223; LEU-226; SER-230; ILE-238; LYS-239; THR-245; LEU-248; TYR-256; VAL-272; GLU-273; ARG-278; PRO-284; THR-291; ARG-352; SER-365; ARG-377; PHE-386; VAL-391; VAL-412; LEU-420; LEU-424; ALA-434 AND ILE-437. - Ref.136"PSEN1 p.Thr116Ile variant in two Korean families with young onset Alzheimer's disease."
Bagyinszky E., Lee H.M., Van Giau V., Koh S.B., Jeong J.H., An S.S.A., Kim S.
Int. J. Mol. Sci. 19:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ILE-116. - Ref.137"Neuropathology and biochemistry of early onset familial Alzheimer's disease caused by presenilin-1 missense mutation Thr116Asn."
Sutovsky S., Smolek T., Turcani P., Petrovic R., Brandoburova P., Jadhav S., Novak P., Attems J., Zilka N.
J. Neural Transm. 125:965-976(2018) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ASN-116. - Ref.138"Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation."
Wang J.C., Alinaghi S., Tafakhori A., Sikora E., Azcona L.J., Karkheiran S., Goate A., Paisan-Ruiz C., Darvish H.
Neurobiol. Aging 62:E15-E17(2018) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS AD3 PHE-142 AND ASP-206. - Ref.139"Novel PSEN1 p.Gly417Ala mutation in a Korean patient with early-onset Alzheimer's disease with parkinsonism."
Giau V.V., Wang M.J., Bagyinszky E., Youn Y.C., An S.S.A., Kim S.
Neurobiol. Aging 72:E13-E17(2018) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 ALA-417. - Ref.140"Phenotypic variability in autosomal dominant familial Alzheimer disease due to the S170F mutation of presenilin-1."
Tiedt H.O., Benjamin B., Niedeggen M., Lueschow A.
Neurodegener. Dis. 18:57-68(2018) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT AD3 PHE-170.
Ref.1
"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease."
Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. , Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 375:754-760(1995) [PubMed] [Europe PMC] [Abstract]
Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. , Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 375:754-760(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS AD3 LEU-146; ARG-163; GLU-246 AND VAL-286, TISSUE SPECIFICITY.
Ref.29
"A new splice variant of glial fibrillary acidic protein GFAPepsilon, interacts with the presenilin proteins."
Nielsen A.L., Holm I.E., Johansen M., Bonven B., Jorgensen P., Jorgensen A.L.
J. Biol. Chem. 277:29983-29991(2002) [PubMed] [Europe PMC] [Abstract]
Nielsen A.L., Holm I.E., Johansen M., Bonven B., Jorgensen P., Jorgensen A.L.
J. Biol. Chem. 277:29983-29991(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GFAP, MUTAGENESIS OF 66-ASP--ASP-72; 76-LYS-TYR-77; 82-VAL-ILE-83; VAL-82 AND 84-MET-LEU-85, CHARACTERIZATION OF VARIANTS AD3 VAL-79 AND LEU-82.
Ref.34
"A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 (Pro117Ser): Comparison of clinical, neuropathological and cell culture phenotypes of Pro117Leu and Pro117Ser mutations."
Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.
J. Alzheimers Dis. 6:31-43(2004) [PubMed] [Europe PMC] [Abstract]
Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.
J. Alzheimers Dis. 6:31-43(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT AD3 SER-117, CHARACTERIZATION OF VARIANTS AD3 LEU-117 AND SER-117.
Ref.40
"Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations."
Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., Serneels L., De Strooper B., Yu G., Bezprozvanny I.
Cell 126:981-993(2006) [PubMed] [Europe PMC] [Abstract]
Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., Serneels L., De Strooper B., Yu G., Bezprozvanny I.
Cell 126:981-993(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANT AD3 VAL-146.
Ref.41
"C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation."
Wang J., Beher D., Nyborg A.C., Shearman M.S., Golde T.E., Goate A.
J. Neurochem. 96:218-227(2006) [PubMed] [Europe PMC] [Abstract]
Wang J., Beher D., Nyborg A.C., Shearman M.S., Golde T.E., Goate A.
J. Neurochem. 96:218-227(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF PAL MOTIF, MUTAGENESIS OF PRO-433; ALA-434 AND LEU-435, CHARACTERIZATION OF VARIANT AD3 PHE-435.
Ref.52
"G206D mutation of presenilin-1 reduces Pen2 interaction, increases Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]
Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., Cheng I.H.
Mol. Neurobiol. 52:1835-1849(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH APH1 AND PEN2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT AD3 ASP-206.
Ref.56
"An atomic structure of human gamma-secretase."
Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., Shi Y.
Nature 525:212-217(2015) [PubMed] [Europe PMC] [Abstract]
Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., Shi Y.
Nature 525:212-217(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS AD3 LEU-213; ILE-237 AND PHE-261, MUTAGENESIS OF ILE-202; LEU-226; LEU-248 AND LEU-424.
Ref.58
"Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3."
Cruts M., Backhovens H., Wang S.-Y., van Gassen G., Theuns J., de Jonghe C., Wehnert A., de Voecht J., de Winter G., Cras P., Bruyland M., Datson N., Weissenbach J., den Dunnen J.T., Martin J.-J., Hendriks L., Van Broeckhoven C.
Hum. Mol. Genet. 4:2363-2372(1995) [PubMed] [Europe PMC] [Abstract]
Cruts M., Backhovens H., Wang S.-Y., van Gassen G., Theuns J., de Jonghe C., Wehnert A., de Voecht J., de Winter G., Cras P., Bruyland M., Datson N., Weissenbach J., den Dunnen J.T., Martin J.-J., Hendriks L., Van Broeckhoven C.
Hum. Mol. Genet. 4:2363-2372(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 THR-143 AND ALA-384.
Ref.59
"Mutations of the presenilin I gene in families with early-onset Alzheimer's disease."
Campion D., Flaman J.-M., Brice A., Hannequin D., Dubois B., Martin C., Moreau V., Charbonnier F., Didierjean O., Tardieu S., Penet C., Puel M., Pasquier F., le Doze F., Bellis G., Calenda A., Heilig R., Martinez M. , Mallet J., Bellis M., Clerget-Darpoux F., Agid Y., Frebourg T.
Hum. Mol. Genet. 4:2373-2377(1995) [PubMed] [Europe PMC] [Abstract]
Campion D., Flaman J.-M., Brice A., Hannequin D., Dubois B., Martin C., Moreau V., Charbonnier F., Didierjean O., Tardieu S., Penet C., Puel M., Pasquier F., le Doze F., Bellis G., Calenda A., Heilig R., Martinez M. , Mallet J., Bellis M., Clerget-Darpoux F., Agid Y., Frebourg T.
Hum. Mol. Genet. 4:2373-2377(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 LEU-82; HIS-115; THR-139; ARG-163; THR-231; LEU-264; VAL-392 AND TYR-410.
Ref.60
"Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene."
Rogaev E.I., Sherrington R., Rogaeva E.A., Levesque G., Ikeda M., Liang Y., Chi H., Lin C., Holman K., Tsuda T., Mar L., Sorbi S., Nacmias B., Piacentini S., Amaducci L., Chumakov I., Cohen D., Lannfelt L. , Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 376:775-778(1995) [PubMed] [Europe PMC] [Abstract]
Rogaev E.I., Sherrington R., Rogaeva E.A., Levesque G., Ikeda M., Liang Y., Chi H., Lin C., Holman K., Tsuda T., Mar L., Sorbi S., Nacmias B., Piacentini S., Amaducci L., Chumakov I., Cohen D., Lannfelt L. , Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 376:775-778(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 VAL-260; VAL-285 AND VAL-392.
Ref.61
"The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families."
Clark R.F., Hutton M., Fuldner R.A., Froelich S., Karran E., Talbot C., Crook R., Lendon C.L., Prihar G., He C., Korenblat K., Martinez A., Wragg M., Busfield F., Behrens M.I., Myers A., Norton J., Morris J. , Mehta N., Pearson C., Lincoln S., Baker M., Duff K., Zehr C., Perez-Tur J., Houlden H., Ruiz A., Ossa J., Lopera F., Arcos M., Madrigal L., Collinge J., Humphreys C., Asworth T., Sarner S., Fox N.C., Harvey R., Kennedy A., Roques P.K., Cline R.T., Phillips C.A., Venter J.C., Forsel L., Axelman K., Lilius L., Johnston J., Cowburn R., Viitanen M., Winblad B., Kosik K.S., Haltia M., Poyhonen M., Dickson D., Mann D., Neary D., Snowden J., Lantos P., Lannfelt L., Rossor M.N., Roberts G.W., Adams M.D., Hardy J., Goate A.M.
Nat. Genet. 11:219-222(1995) [PubMed] [Europe PMC] [Abstract]
Clark R.F., Hutton M., Fuldner R.A., Froelich S., Karran E., Talbot C., Crook R., Lendon C.L., Prihar G., He C., Korenblat K., Martinez A., Wragg M., Busfield F., Behrens M.I., Myers A., Norton J., Morris J. , Mehta N., Pearson C., Lincoln S., Baker M., Duff K., Zehr C., Perez-Tur J., Houlden H., Ruiz A., Ossa J., Lopera F., Arcos M., Madrigal L., Collinge J., Humphreys C., Asworth T., Sarner S., Fox N.C., Harvey R., Kennedy A., Roques P.K., Cline R.T., Phillips C.A., Venter J.C., Forsel L., Axelman K., Lilius L., Johnston J., Cowburn R., Viitanen M., Winblad B., Kosik K.S., Haltia M., Poyhonen M., Dickson D., Mann D., Neary D., Snowden J., Lantos P., Lannfelt L., Rossor M.N., Roberts G.W., Adams M.D., Hardy J., Goate A.M.
Nat. Genet. 11:219-222(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 VAL-139; VAL-146; TYR-163; THR-267; ALA-280 AND GLY-280.
Ref.62
"The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology."
Lemere C.A., Lopera F., Kosik K.S., Lendon C.L., Ossa J., Saido T.C., Yamaguchi H., Ruiz A., Martinez A., Madrigal L., Hincapie L., Arango J.C., Anthony D.C., Koo E.H., Goate A.M., Selkoe D.J., Arango J.C.
Nat. Med. 2:1146-1150(1996) [PubMed] [Europe PMC] [Abstract]
Lemere C.A., Lopera F., Kosik K.S., Lendon C.L., Ossa J., Saido T.C., Yamaguchi H., Ruiz A., Martinez A., Madrigal L., Hincapie L., Arango J.C., Anthony D.C., Koo E.H., Goate A.M., Selkoe D.J., Arango J.C.
Nat. Med. 2:1146-1150(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ALA-280, INVOLVEMENT IN AD3.
Ref.63
"Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families."
Kamino K., Sato S., Sakaki Y., Yoshiiwa A., Nishiwaki Y., Takeda H., Tanabe H., Nishimura T., Li K., St George-Hyslop P.H., Miki T., Ogihara T.
Neurosci. Lett. 208:195-198(1996) [PubMed] [Europe PMC] [Abstract]
Kamino K., Sato S., Sakaki Y., Yoshiiwa A., Nishiwaki Y., Takeda H., Tanabe H., Nishimura T., Li K., St George-Hyslop P.H., Miki T., Ogihara T.
Neurosci. Lett. 208:195-198(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 PHE-96; ARG-163 AND THR-213.
Ref.64
"Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation."
Crook R., Ellis R., Shanks M., Thal L.J., Perez-Tur J., Baker M., Hutton M., Haltia T., Hardy J., Galasko D.
Ann. Neurol. 42:124-128(1997) [PubMed] [Europe PMC] [Abstract]
Crook R., Ellis R., Shanks M., Thal L.J., Perez-Tur J., Baker M., Hutton M., Haltia T., Hardy J., Galasko D.
Ann. Neurol. 42:124-128(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ASP-135.
Ref.65
"E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles."
Lendon C.L., Martinez A., Behrens I.M., Kosik K.S., Madrigal L., Norton J., Neuman R., Myers A., Busfield F., Wragg M., Arcos M., Arango-Viana J.C., Ossa J., Ruiz A., Goate A.M., Lopera F.
Hum. Mutat. 10:186-195(1997) [PubMed] [Europe PMC] [Abstract]
Lendon C.L., Martinez A., Behrens I.M., Kosik K.S., Madrigal L., Norton J., Neuman R., Myers A., Busfield F., Wragg M., Arcos M., Arango-Viana J.C., Ossa J., Ruiz A., Goate A.M., Lopera F.
Hum. Mutat. 10:186-195(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ALA-280.
Ref.66
"Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype."
Kwok J.B.J., Taddei K., Hallupp M., Fisher C., Brooks W.S., Broe G.A., Hardy J., Fulham M.J., Nicholson G.A., Stell R., St George-Hyslop P.H., Fraser P.E., Kakulas B., Clarnette R., Relkin N., Gandy S.E., Schofield P.R., Martins R.N.
NeuroReport 8:1537-1542(1997) [PubMed] [Europe PMC] [Abstract]
Kwok J.B.J., Taddei K., Hallupp M., Fisher C., Brooks W.S., Broe G.A., Hardy J., Fulham M.J., Nicholson G.A., Stell R., St George-Hyslop P.H., Fraser P.E., Kakulas B., Clarnette R., Relkin N., Gandy S.E., Schofield P.R., Martins R.N.
NeuroReport 8:1537-1542(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 THR-233 AND THR-278.
Ref.67
"A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease."
Ramirez-Duenas M.G., Rogaeva E.A., Leal C.A., Lin C., Ramirez-Casillas G.A., Hernandez-Romo J.A., St George-Hyslop P.H., Cantu J.M.
Ann. Genet. 41:149-153(1998) [PubMed] [Europe PMC] [Abstract]
Ramirez-Duenas M.G., Rogaeva E.A., Leal C.A., Lin C., Ramirez-Casillas G.A., Hernandez-Romo J.A., St George-Hyslop P.H., Cantu J.M.
Ann. Genet. 41:149-153(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PRO-171.
Ref.70
"Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease."
Cruts M., van Duijn C.M., Backhovens H., van den Broeck M., Wehnert A., Serneels S., Sherrington R., Hutton M., Hardy J., St George-Hyslop P.H., Hofman A., van Broeckhoven C.
Hum. Mol. Genet. 7:43-51(1998) [PubMed] [Europe PMC] [Abstract]
Cruts M., van Duijn C.M., Backhovens H., van den Broeck M., Wehnert A., Serneels S., Sherrington R., Hutton M., Hardy J., St George-Hyslop P.H., Hofman A., van Broeckhoven C.
Hum. Mol. Genet. 7:43-51(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 VAL-79; CYS-115 AND VAL-231, VARIANT GLY-318.
Ref.71
"Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene."
Poorkaj P., Sharma V., Anderson L., Nemens E., Alonso M.E., Orr H., White J., Heston L., Bird T.D., Schellenberg G.D.
Hum. Mutat. 11:216-221(1998) [PubMed] [Europe PMC] [Abstract]
Poorkaj P., Sharma V., Anderson L., Nemens E., Alonso M.E., Orr H., White J., Heston L., Bird T.D., Schellenberg G.D.
Hum. Mutat. 11:216-221(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 ASP-120; ARG-163; VAL-209; VAL-260; LEU-264; TYR-410 AND PRO-426.
Ref.72
"Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification."
Besancon R., Lorenzi A., Cruts M., Radawiec S., Sturtz F., Broussolle E., Chazot G., van Broeckhoven C., Chamba G., Vandenberghe A.
Hum. Mutat. 11:481-481(1998) [PubMed] [Europe PMC] [Abstract]
Besancon R., Lorenzi A., Cruts M., Radawiec S., Sturtz F., Broussolle E., Chazot G., van Broeckhoven C., Chamba G., Vandenberghe A.
Hum. Mutat. 11:481-481(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 GLU-378.
Ref.73
"De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases."
Dumanchin C., Brice A., Campion D., Hannequin D., Martin C., Moreau V., Agid Y., Martinez M., Clerget-Darpoux F., Frebourg T.
J. Med. Genet. 35:672-673(1998) [PubMed] [Europe PMC] [Abstract]
Dumanchin C., Brice A., Campion D., Hannequin D., Martin C., Moreau V., Agid Y., Martinez M., Clerget-Darpoux F., Frebourg T.
J. Med. Genet. 35:672-673(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 LYS-139.
Ref.74
"A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years."
Wisniewski T., Dowjat W.K., Buxbaum J.D., Khorkova O., Efthimiopoulos S., Kulczycki J., Lojkowska W., Wegiel J., Wisniewski H.M., Frangione B.
NeuroReport 9:217-221(1998) [PubMed] [Europe PMC] [Abstract]
Wisniewski T., Dowjat W.K., Buxbaum J.D., Khorkova O., Efthimiopoulos S., Kulczycki J., Lojkowska W., Wegiel J., Wisniewski H.M., Frangione B.
NeuroReport 9:217-221(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 LEU-117.
Ref.75
"Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease."
Taddei K., Kwok J.B., Kril J.J., Halliday G.M., Creasey H., Hallupp M., Fisher C., Brooks W.S., Chung C., Andrews C., Masters C.L., Schofield P.R., Martins R.N.
NeuroReport 9:3335-3339(1998) [PubMed] [Europe PMC] [Abstract]
Taddei K., Kwok J.B., Kril J.J., Halliday G.M., Creasey H., Hallupp M., Fisher C., Brooks W.S., Chung C., Andrews C., Masters C.L., Schofield P.R., Martins R.N.
NeuroReport 9:3335-3339(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 LEU-169 AND GLN-436.
Ref.77
"Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum."
Campion D., Dumanchin C., Hannequin D., Dubois B., Belliard S., Puel M., Thomas-Anterion C., Michon A., Martin C., Charbonnier F., Raux G., Camuzat A., Penet C., Mesnage V., Martinez M., Clerget-Darpoux F., Brice A., Frebourg T.
Am. J. Hum. Genet. 65:664-670(1999) [PubMed] [Europe PMC] [Abstract]
Campion D., Dumanchin C., Hannequin D., Dubois B., Belliard S., Puel M., Thomas-Anterion C., Michon A., Martin C., Charbonnier F., Raux G., Camuzat A., Penet C., Mesnage V., Martinez M., Clerget-Darpoux F., Brice A., Frebourg T.
Am. J. Hum. Genet. 65:664-670(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 LEU-82; HIS-115; ASP-120; THR-139; LEU-146; ILE-147; ARG-163; CYS-165; TRP-173; THR-231; THR-233; PRO-235; LEU-264; ILE-390; VAL-392 AND TYR-410, VARIANT GLY-318.
Ref.78
"Pathogenic presenilin 1 mutations (P436S and I143F) in early-onset Alzheimer's disease in the UK."
Palmer M.S., Beck J.A., Campbell T.A., Humphries C.B., Roques P.K., Fox N.C., Harvey R., Rossor M.N., Collinge J.
Hum. Mutat. 13:256-256(1999) [PubMed] [Europe PMC] [Abstract]
Palmer M.S., Beck J.A., Campbell T.A., Humphries C.B., Roques P.K., Fox N.C., Harvey R., Rossor M.N., Collinge J.
Hum. Mutat. 13:256-256(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 PHE-143 AND SER-436.
Ref.79
"A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease."
Sugiyama N., Suzuki K., Matsumura T., Kawanishi C., Onishi H., Yamada Y., Iseki E., Kosaka K.
Hum. Mutat. 14:90-90(1999) [PubMed] [Europe PMC] [Abstract]
Sugiyama N., Suzuki K., Matsumura T., Kawanishi C., Onishi H., Yamada Y., Iseki E., Kosaka K.
Hum. Mutat. 14:90-90(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ARG-209.
Ref.80
"DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations."
Aldudo J., Bullido M.J., Valdivieso F.
Hum. Mutat. 14:433-439(1999) [PubMed] [Europe PMC] [Abstract]
Aldudo J., Bullido M.J., Valdivieso F.
Hum. Mutat. 14:433-439(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 LEU-233; ARG-282 AND THR-409, VARIANT GLY-318.
Ref.81
"A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures."
Ezquerra M., Carnero C., Blesa R., Gelpi J.L., Ballesta F., Oliva R.
Neurology 52:566-570(1999) [PubMed] [Europe PMC] [Abstract]
Ezquerra M., Carnero C., Blesa R., Gelpi J.L., Ballesta F., Oliva R.
Neurology 52:566-570(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PRO-169.
Ref.82
"Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene."
Smith M.J., Gardner R.J., Knight M.A., Forrest S.M., Beyreuther K., Storey E., McLean C.A., Cotton R.G., Cappal R., Masters C.L.
NeuroReport 10:503-507(1999) [PubMed] [Europe PMC] [Abstract]
Smith M.J., Gardner R.J., Knight M.A., Forrest S.M., Beyreuther K., Storey E., McLean C.A., Cotton R.G., Cappal R., Masters C.L.
NeuroReport 10:503-507(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PRO-219.
Ref.83
"A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease."
Romero I., Joergensen P., Bolwig G., Fraser P.E., Rogaeva E., Mann D., Havsager A.-M., Joergensen A.L.
NeuroReport 10:2255-2260(1999) [PubMed] [Europe PMC] [Abstract]
Romero I., Joergensen P., Bolwig G., Fraser P.E., Rogaeva E., Mann D., Havsager A.-M., Joergensen A.L.
NeuroReport 10:2255-2260(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ASN-116.
Ref.84
"High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes."
Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.
Am. J. Hum. Genet. 66:110-117(2000) [PubMed] [Europe PMC] [Abstract]
Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.
Am. J. Hum. Genet. 66:110-117(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 VAL-79; LEU-105 AND VAL-139, VARIANT GLY-318.
Ref.85
"Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy."
Yasuda M., Maeda S., Kawamata T., Tamaoka A., Yamamoto Y., Kuroda S., Maeda K., Tanaka C.
J. Neurol. Neurosurg. Psych. 68:220-223(2000) [PubMed] [Europe PMC] [Abstract]
Yasuda M., Maeda S., Kawamata T., Tamaoka A., Yamamoto Y., Kuroda S., Maeda K., Tanaka C.
J. Neurol. Neurosurg. Psych. 68:220-223(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 SER-405.
Ref.86
"The presenilin 1 C92S mutation increases abeta 42 production."
Lewis P.A., Perez-Tur J., Golde T.E., Hardy J.
Biochem. Biophys. Res. Commun. 277:261-263(2000) [PubMed] [Europe PMC] [Abstract]
Lewis P.A., Perez-Tur J., Golde T.E., Hardy J.
Biochem. Biophys. Res. Commun. 277:261-263(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 SER-92.
Ref.88
"Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia."
Arango D., Cruts M., Torres O., Backhovens H., Serrano M.L., Villareal E., Montanes P., Matallana D., Cano C., Van Broeckhoven C., Jacquier M.
Am. J. Med. Genet. 103:138-143(2001) [PubMed] [Europe PMC] [Abstract]
Arango D., Cruts M., Torres O., Backhovens H., Serrano M.L., Villareal E., Montanes P., Matallana D., Cano C., Van Broeckhoven C., Jacquier M.
Am. J. Med. Genet. 103:138-143(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 MET-94; THR-143 AND ALA-280, VARIANT GLY-318.
Ref.89
"Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation."
Dermaut B., Kumar-Singh S., De Jonghe C., Cruts M., Loefgren A., Luebke U., Cras P., Dom R., De Deyn P.P., Martin J.J., Van Broeckhoven C.
Brain 124:2383-2392(2001) [PubMed] [Europe PMC] [Abstract]
Dermaut B., Kumar-Singh S., De Jonghe C., Cruts M., Loefgren A., Luebke U., Cras P., Dom R., De Deyn P.P., Martin J.J., Van Broeckhoven C.
Brain 124:2383-2392(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 VAL-282, CHARACTERIZATION OF VARIANT AD3 VAL-282.
Ref.90
Cited for: VARIANT AD3 GLU-431.
Ref.91
"A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families."
Athan E.S., Williamson J., Ciappa A., Santana V., Romas S.N., Lee J.H., Rondon H., Lantigua R.A., Medrano M., Torres M., Arawaka S., Rogaeva E., Song Y.-Q., Sato C., Kawarai T., Fafel K.C., Boss M.A., Seltzer W.K. , Stern Y., St George-Hyslop P.H., Tycko B., Mayeux R.
JAMA 286:2257-2263(2001) [PubMed] [Europe PMC] [Abstract]
Athan E.S., Williamson J., Ciappa A., Santana V., Romas S.N., Lee J.H., Rondon H., Lantigua R.A., Medrano M., Torres M., Arawaka S., Rogaeva E., Song Y.-Q., Sato C., Kawarai T., Fafel K.C., Boss M.A., Seltzer W.K. , Stern Y., St George-Hyslop P.H., Tycko B., Mayeux R.
JAMA 286:2257-2263(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ALA-206.
Ref.92
"Very early onset Alzheimer's disease with spastic paraparesis associated with a novel presenilin 1 mutation (Phe237Ile)."
Sodeyama N., Iwata T., Ishikawa K., Mizusawa H., Yamada M., Itoh Y., Otomo E., Matsushita M., Komatsuzaki Y.
J. Neurol. Neurosurg. Psych. 71:556-557(2001) [PubMed] [Europe PMC] [Abstract]
Sodeyama N., Iwata T., Ishikawa K., Mizusawa H., Yamada M., Itoh Y., Otomo E., Matsushita M., Komatsuzaki Y.
J. Neurol. Neurosurg. Psych. 71:556-557(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ILE-237.
Ref.93
"Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations."
Rogaeva E.A., Fafel K.C., Song Y.Q., Medeiros H., Sato C., Liang Y., Richard E., Rogaev E.I., Frommelt P., Sadovnick A.D., Meschino W., Rockwood K., Boss M.A., Mayeux R., St George-Hyslop P.
Neurology 57:621-625(2001) [PubMed] [Europe PMC] [Abstract]
Rogaeva E.A., Fafel K.C., Song Y.Q., Medeiros H., Sato C., Liang Y., Richard E., Rogaev E.I., Frommelt P., Sadovnick A.D., Meschino W., Rockwood K., Boss M.A., Mayeux R., St George-Hyslop P.
Neurology 57:621-625(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 GLN-35; VAL-79; CYS-115; ASN-116; THR-143; ILE-146; LEU-146; VAL-146; TYR-156 DELINS PHE-THR-TYR; ARG-163; LEU-177; SER-177; PRO-178; ALA-206; SER-206; GLU-209; LEU-213; ARG-222; THR-231; LEU-233; PRO-235; PHE-261; ARG-274; ARG-352 INS; ILE-354; GLN-358; TYR-365; VAL-394; PHE-418; GLU-431; PHE-435 AND VAL-439, VARIANT GLY-318.
Ref.94
"Molecular evidence of presenilin 1 mutation in familial early onset dementia."
Matsubara-Tsutsui M., Yasuda M., Yamagata H., Nomura T., Taguchi K., Kohara K., Miyoshi K., Miki T.
Am. J. Med. Genet. 114:292-298(2002) [PubMed] [Europe PMC] [Abstract]
Matsubara-Tsutsui M., Yasuda M., Yamagata H., Nomura T., Taguchi K., Kohara K., Miyoshi K., Miki T.
Am. J. Med. Genet. 114:292-298(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 SER-266.
Ref.95
"A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances."
Queralt R., Ezquerra M., Lleo A., Castellvi M., Gelpi J., Ferrer I., Acarin N., Pasarin L., Blesa R., Oliva R.
J. Neurol. Neurosurg. Psych. 72:266-269(2002) [PubMed] [Europe PMC] [Abstract]
Queralt R., Ezquerra M., Lleo A., Castellvi M., Gelpi J., Ferrer I., Acarin N., Pasarin L., Blesa R., Oliva R.
J. Neurol. Neurosurg. Psych. 72:266-269(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 LEU-89.
Ref.96
"Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities."
O'Riordan S., McMonagle P., Janssen J.C., Fox N.C., Farrell M., Collinge J., Rossor M.N., Hutchinson M.
Neurology 59:1108-1110(2002) [PubMed] [Europe PMC] [Abstract]
O'Riordan S., McMonagle P., Janssen J.C., Fox N.C., Farrell M., Collinge J., Rossor M.N., Hutchinson M.
Neurology 59:1108-1110(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 GLY-280.
Ref.97
"Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production."
Moehlmann T., Winkler E., Xia X., Edbauer D., Murrell J., Capell A., Kaether C., Zheng H., Ghetti B., Haass C., Steiner H.
Proc. Natl. Acad. Sci. U.S.A. 99:8025-8030(2002) [PubMed] [Europe PMC] [Abstract]
Moehlmann T., Winkler E., Xia X., Edbauer D., Murrell J., Capell A., Kaether C., Zheng H., Ghetti B., Haass C., Steiner H.
Proc. Natl. Acad. Sci. U.S.A. 99:8025-8030(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PRO-166.
Ref.98
"A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease."
Bertoli-Avella A.M., Marcheco Teruel B., Llibre Rodriguez J.J., Gomez Viera N., Borrajero-Martinez I., Severijnen E.A., Joosse M., van Duijn C.M., Heredero Baute L., Heutink P.
Neurogenetics 4:97-104(2002) [PubMed] [Europe PMC] [Abstract]
Bertoli-Avella A.M., Marcheco Teruel B., Llibre Rodriguez J.J., Gomez Viera N., Borrajero-Martinez I., Severijnen E.A., Joosse M., van Duijn C.M., Heredero Baute L., Heutink P.
Neurogenetics 4:97-104(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 MET-174.
Ref.99
"Presenilin-1 mutation L271V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy."
Kwok J.B.J., Halliday G.M., Brooks W.S., Dolios G., Laudon H., Murayama O., Hallupp M., Badenhop R.F., Vickers J., Wang R., Naslund J., Takashima A., Gandy S.E., Schofield P.R.
J. Biol. Chem. 278:6748-6754(2003) [PubMed] [Europe PMC] [Abstract]
Kwok J.B.J., Halliday G.M., Brooks W.S., Dolios G., Laudon H., Murayama O., Hallupp M., Badenhop R.F., Vickers J., Wang R., Naslund J., Takashima A., Gandy S.E., Schofield P.R.
J. Biol. Chem. 278:6748-6754(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 VAL-271.
Ref.100
"Early onset familial Alzheimer's disease: Mutation frequency in 31 families."
Janssen J.C., Beck J.A., Campbell T.A., Dickinson A., Fox N.C., Harvey R.J., Houlden H., Rossor M.N., Collinge J.
Neurology 60:235-239(2003) [PubMed] [Europe PMC] [Abstract]
Janssen J.C., Beck J.A., Campbell T.A., Dickinson A., Fox N.C., Harvey R.J., Houlden H., Rossor M.N., Collinge J.
Neurology 60:235-239(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 CYS-115; ILE-146; VAL-153; CYS-154; ILE-168 DEL; PRO-171; ASP-184; PHE-229; VAL-235; LEU-237; VAL-260; PHE-263; HIS-269; MET-377 AND VAL-378, VARIANT GLY-318.
Ref.101
"A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques."
Dermaut B., Kumar-Singh S., Engelborghs S., Theuns J., Rademakers R., Saerens J., Pickut B.A., Peeters K., van den Broeck M., Vennekens K., Claes S., Cruts M., Cras P., Martin J.J., Van Broeckhoven C., De Deyn P.P.
Ann. Neurol. 55:617-626(2004) [PubMed] [Europe PMC] [Abstract]
Dermaut B., Kumar-Singh S., Engelborghs S., Theuns J., Rademakers R., Saerens J., Pickut B.A., Peeters K., van den Broeck M., Vennekens K., Claes S., Cruts M., Cras P., Martin J.J., Van Broeckhoven C., De Deyn P.P.
Ann. Neurol. 55:617-626(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PIDB VAL-183, CHARACTERIZATION OF VARIANTS AD3 THR-143 AND VAL-282, CHARACTERIZATION OF VARIANT PIDB VAL-183.
Ref.102
"A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis."
Ataka S., Tomiyama T., Takuma H., Yamashita T., Shimada H., Tsutada T., Kawabata K., Mori H., Miki T.
Arch. Neurol. 61:1773-1776(2004) [PubMed] [Europe PMC] [Abstract]
Ataka S., Tomiyama T., Takuma H., Yamashita T., Shimada H., Tsutada T., Kawabata K., Mori H., Miki T.
Arch. Neurol. 61:1773-1776(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PRO-85, CHARACTERIZATION OF VARIANT AD3 PRO-85.
Ref.103
"A presenilin 1 R278I mutation presenting with language impairment."
Godbolt A.K., Beck J.A., Collinge J., Garrard P., Warren J.D., Fox N.C., Rossor M.N.
Neurology 63:1702-1704(2004) [PubMed] [Europe PMC] [Abstract]
Godbolt A.K., Beck J.A., Collinge J., Garrard P., Warren J.D., Fox N.C., Rossor M.N.
Neurology 63:1702-1704(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ILE-278.
Ref.104
"A novel presenilin 1 mutation (Y154N) in a patient with early onset Alzheimer's disease with spastic paraparesis."
Hattori S., Sakuma K., Wakutani Y., Wada K., Shimoda M., Urakami K., Kowa H., Nakashima K.
Neurosci. Lett. 368:319-322(2004) [PubMed] [Europe PMC] [Abstract]
Hattori S., Sakuma K., Wakutani Y., Wada K., Shimoda M., Urakami K., Kowa H., Nakashima K.
Neurosci. Lett. 368:319-322(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ASN-154.
Ref.105
"Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life."
Snider B.J., Norton J., Coats M.A., Chakraverty S., Hou C.E., Jervis R., Lendon C.L., Goate A.M., McKeel D.W. Jr., Morris J.C.
Arch. Neurol. 62:1821-1830(2005) [PubMed] [Europe PMC] [Abstract]
Snider B.J., Norton J., Coats M.A., Chakraverty S., Hou C.E., Jervis R., Lendon C.L., Goate A.M., McKeel D.W. Jr., Morris J.C.
Arch. Neurol. 62:1821-1830(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PHE-170.
Ref.108
"Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40."
Kumar-Singh S., Theuns J., Van Broeck B., Pirici D., Vennekens K., Corsmit E., Cruts M., Dermaut B., Wang R., Van Broeckhoven C.
Hum. Mutat. 27:686-695(2006) [PubMed] [Europe PMC] [Abstract]
Kumar-Singh S., Theuns J., Van Broeck B., Pirici D., Vennekens K., Corsmit E., Cruts M., Dermaut B., Wang R., Van Broeckhoven C.
Hum. Mutat. 27:686-695(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AD3 VAL-79; THR-143; VAL-231; PHE-262; PHE-263; VAL-282 AND ALA-384.
Ref.109
"Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer's disease in Mexican families."
Yescas P., Huertas-Vazquez A., Villarreal-Molina M.T., Rasmussen A., Tusie-Luna M.T., Lopez M., Canizales-Quinteros S., Alonso M.E.
Neurogenetics 7:195-200(2006) [PubMed] [Europe PMC] [Abstract]
Yescas P., Huertas-Vazquez A., Villarreal-Molina M.T., Rasmussen A., Tusie-Luna M.T., Lopez M., Canizales-Quinteros S., Alonso M.E.
Neurogenetics 7:195-200(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 GLU-431.
Ref.110
"The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families."
Murrell J., Ghetti B., Cochran E., Macias-Islas M.A., Medina L., Varpetian A., Cummings J.L., Mendez M.F., Kawas C., Chui H., Ringman J.M.
Neurogenetics 7:277-279(2006) [PubMed] [Europe PMC] [Abstract]
Murrell J., Ghetti B., Cochran E., Macias-Islas M.A., Medina L., Varpetian A., Cummings J.L., Mendez M.F., Kawas C., Chui H., Ringman J.M.
Neurogenetics 7:277-279(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 GLU-431.
Ref.111
"Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation."
Kauwe J.S., Jacquart S., Chakraverty S., Wang J., Mayo K., Fagan A.M., Holtzman D.M., Morris J.C., Goate A.M.
Ann. Neurol. 61:446-453(2007) [PubMed] [Europe PMC] [Abstract]
Kauwe J.S., Jacquart S., Chakraverty S., Wang J., Mayo K., Fagan A.M., Holtzman D.M., Morris J.C., Goate A.M.
Ann. Neurol. 61:446-453(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 VAL-79, CHARACTERIZATION OF VARIANT AD3 VAL-79.
Ref.112
"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype."
Piccini A., Zanusso G., Borghi R., Noviello C., Monaco S., Russo R., Damonte G., Armirotti A., Gelati M., Giordano R., Zambenedetti P., Russo C., Ghetti B., Tabaton M.
Arch. Neurol. 64:738-745(2007) [PubMed] [Europe PMC] [Abstract]
Piccini A., Zanusso G., Borghi R., Noviello C., Monaco S., Russo R., Damonte G., Armirotti A., Gelati M., Giordano R., Zambenedetti P., Russo C., Ghetti B., Tabaton M.
Arch. Neurol. 64:738-745(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PHE-170.
Ref.113
"Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor."
Litterst C., Georgakopoulos A., Shioi J., Ghersi E., Wisniewski T., Wang R., Ludwig A., Robakis N.K.
J. Biol. Chem. 282:16155-16163(2007) [PubMed] [Europe PMC] [Abstract]
Litterst C., Georgakopoulos A., Shioi J., Ghersi E., Wisniewski T., Wang R., Ludwig A., Robakis N.K.
J. Biol. Chem. 282:16155-16163(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AD3 LEU-117; LEU-146; GLU-246; VAL-260; LEU-264 AND GLY-280, FUNCTION, MUTAGENESIS OF ASP-257.
Ref.115
"Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta."
Shimojo M., Sahara N., Mizoroki T., Funamoto S., Morishima-Kawashima M., Kudo T., Takeda M., Ihara Y., Ichinose H., Takashima A.
J. Biol. Chem. 283:16488-16496(2008) [PubMed] [Europe PMC] [Abstract]
Shimojo M., Sahara N., Mizoroki T., Funamoto S., Morishima-Kawashima M., Kudo T., Takeda M., Ihara Y., Ichinose H., Takashima A.
J. Biol. Chem. 283:16488-16496(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AD3 THR-213.
Ref.116
"Novel PSEN1 mutation in a Bulgarian patient with very early-onset Alzheimer's disease, spastic paraparesis, and extrapyramidal signs."
Dintchov Traykov L., Mehrabian S., Van den Broeck M., Radoslavova Raycheva M., Cruts M., Kirilova Jordanova A., Van Broeckhoven C.
Am. J. Alzheimers Dis. Other Demen. 24:404-407(2009) [PubMed] [Europe PMC] [Abstract]
Dintchov Traykov L., Mehrabian S., Van den Broeck M., Radoslavova Raycheva M., Cruts M., Kirilova Jordanova A., Van Broeckhoven C.
Am. J. Alzheimers Dis. Other Demen. 24:404-407(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 VAL-381.
Ref.117
"Presenilin1 G217R mutation linked to Alzheimer disease with cotton wool plaques."
Norton J.B., Cairns N.J., Chakraverty S., Wang J., Levitch D., Galvin J.E., Goate A.
Neurology 73:480-482(2009) [PubMed] [Europe PMC] [Abstract]
Norton J.B., Cairns N.J., Chakraverty S., Wang J., Levitch D., Galvin J.E., Goate A.
Neurology 73:480-482(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ARG-217, CHARACTERIZATION OF VARIANT AD3 ARG-217.
Ref.118
"Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation."
Bruni A.C., Bernardi L., Colao R., Rubino E., Smirne N., Frangipane F., Terni B., Curcio S.A., Mirabelli M., Clodomiro A., Di Lorenzo R., Maletta R., Anfossi M., Gallo M., Geracitano S., Tomaino C., Muraca M.G., Leotta A. , Lio S.G., Pinessi L., Rainero I., Sorbi S., Nee L., Milan G., Pappata S., Postiglione A., Abbamondi N., Forloni G., St George Hyslop P., Rogaeva E., Bugiani O., Giaccone G., Foncin J.F., Spillantini M.G., Puccio G.
Neurology 74:798-806(2010) [PubMed] [Europe PMC] [Abstract]
Bruni A.C., Bernardi L., Colao R., Rubino E., Smirne N., Frangipane F., Terni B., Curcio S.A., Mirabelli M., Clodomiro A., Di Lorenzo R., Maletta R., Anfossi M., Gallo M., Geracitano S., Tomaino C., Muraca M.G., Leotta A. , Lio S.G., Pinessi L., Rainero I., Sorbi S., Nee L., Milan G., Pappata S., Postiglione A., Abbamondi N., Forloni G., St George Hyslop P., Rogaeva E., Bugiani O., Giaccone G., Foncin J.F., Spillantini M.G., Puccio G.
Neurology 74:798-806(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 LEU-146.
Ref.119
"A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity."
Heilig E.A., Xia W., Shen J., Kelleher R.J. III
J. Biol. Chem. 285:22350-22359(2010) [PubMed] [Europe PMC] [Abstract]
Heilig E.A., Xia W., Shen J., Kelleher R.J. III
J. Biol. Chem. 285:22350-22359(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PHE-435, CHARACTERIZATION OF VARIANTS AD3 PHE-435; GLN-436 AND SER-436, MUTAGENESIS OF PRO-433 AND LEU-435, FUNCTION.
Ref.120
"Clinical phenotype of G206D mutation in the presenilin 1 gene in pathologically confirmed familial Alzheimer's disease."
Wu Y.Y., Cheng I.H., Lee C.C., Chiu M.J., Lee M.J., Chen T.F., Hsu J.L.
J. Alzheimers Dis. 25:145-150(2011) [PubMed] [Europe PMC] [Abstract]
Wu Y.Y., Cheng I.H., Lee C.C., Chiu M.J., Lee M.J., Chen T.F., Hsu J.L.
J. Alzheimers Dis. 25:145-150(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ASP-206.
Ref.122
"A novel PSEN1 gene mutation (L235R) associated with familial early-onset Alzheimer's disease."
Antonell A., Balasa M., Oliva R., Llado A., Bosch B., Fabregat N., Fortea J., Molinuevo J.L., Sanchez-Valle R.
Neurosci. Lett. 496:40-42(2011) [PubMed] [Europe PMC] [Abstract]
Antonell A., Balasa M., Oliva R., Llado A., Bosch B., Fabregat N., Fortea J., Molinuevo J.L., Sanchez-Valle R.
Neurosci. Lett. 496:40-42(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ARG-235.
Ref.123
"Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of gamma-secretase."
Chau D.M., Crump C.J., Villa J.C., Scheinberg D.A., Li Y.M.
J. Biol. Chem. 287:17288-17296(2012) [PubMed] [Europe PMC] [Abstract]
Chau D.M., Crump C.J., Villa J.C., Scheinberg D.A., Li Y.M.
J. Biol. Chem. 287:17288-17296(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AD3 LEU-146; ARG-163 AND ALA-280.
Ref.124
"Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients."
Lohmann E., Guerreiro R.J., Erginel-Unaltuna N., Gurunlian N., Bilgic B., Gurvit H., Hanagasi H.A., Luu N., Emre M., Singleton A.
Neurobiol. Aging 33:1850.E17-1850.E27(2012) [PubMed] [Europe PMC] [Abstract]
Lohmann E., Guerreiro R.J., Erginel-Unaltuna N., Gurunlian N., Bilgic B., Gurvit H., Hanagasi H.A., Luu N., Emre M., Singleton A.
Neurobiol. Aging 33:1850.E17-1850.E27(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 ARG-134; ARG-163 AND VAL-262, VARIANT TYR-214.
Ref.125
"Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's disease."
Kerchner G.A., Holbrook K.
Neurosci. Lett. 531:142-144(2012) [PubMed] [Europe PMC] [Abstract]
Kerchner G.A., Holbrook K.
Neurosci. Lett. 531:142-144(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PHE-159.
Ref.126
"Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified gamma-secretase complexes."
Cacquevel M., Aeschbach L., Houacine J., Fraering P.C.
PLoS ONE 7:E35133-E35133(2012) [PubMed] [Europe PMC] [Abstract]
Cacquevel M., Aeschbach L., Houacine J., Fraering P.C.
PLoS ONE 7:E35133-E35133(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AD3 PRO-166 AND GLN-436, MUTAGENESIS OF ASP-257 AND ASP-385.
Ref.127
"Trans-dominant negative effects of pathogenic PSEN1 mutations on gamma-secretase activity and Abeta production."
Heilig E.A., Gutti U., Tai T., Shen J., Kelleher R.J. III
J. Neurosci. 33:11606-11617(2013) [PubMed] [Europe PMC] [Abstract]
Heilig E.A., Gutti U., Tai T., Shen J., Kelleher R.J. III
J. Neurosci. 33:11606-11617(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AD3 PRO-166; ILE-278; ALA-384; VAL-392; TYR-410 AND PHE-435.
Ref.128
"A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very early onset and unusually fast progressing dementia as well as lysosomal inclusions typically seen in Kufs disease."
Dolzhanskaya N., Gonzalez M.A., Sperziani F., Stefl S., Messing J., Wen G.Y., Alexov E., Zuchner S., Velinov M.
J. Alzheimers Dis. 39:23-27(2014) [PubMed] [Europe PMC] [Abstract]
Dolzhanskaya N., Gonzalez M.A., Sperziani F., Stefl S., Messing J., Wen G.Y., Alexov E., Zuchner S., Velinov M.
J. Alzheimers Dis. 39:23-27(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PHE-381.
Ref.129
"Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease."
Cornejo-Olivas M.R., Yu C.E., Mazzetti P., Mata I.F., Meza M., Lindo-Samanamud S., Leverenz J.B., Bird T.D.
Neurosci. Lett. 563:140-143(2014) [PubMed] [Europe PMC] [Abstract]
Cornejo-Olivas M.R., Yu C.E., Mazzetti P., Mata I.F., Meza M., Lindo-Samanamud S., Leverenz J.B., Bird T.D.
Neurosci. Lett. 563:140-143(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 VAL-153.
Ref.130
"A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease."
Luedecke D., Becktepe J.S., Lehmbeck J.T., Finckh U., Yamamoto R., Jahn H., Boelmans K.
Neurosci. Lett. 566:115-119(2014) [PubMed] [Europe PMC] [Abstract]
Luedecke D., Becktepe J.S., Lehmbeck J.T., Finckh U., Yamamoto R., Jahn H., Boelmans K.
Neurosci. Lett. 566:115-119(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 VAL-275.
Ref.131
"Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease."
Achouri-Rassas A., Ben Ali N., Fray S., Hadj Fredj S., Kechaou M., Zakraoui N.O., Cherif A., Chabbi S., Anane N., Messaoud T., Gouider R., Belal S.
Neurobiol. Aging 36:2904.E09-2904.E11(2015) [PubMed] [Europe PMC] [Abstract]
Achouri-Rassas A., Ben Ali N., Fray S., Hadj Fredj S., Kechaou M., Zakraoui N.O., Cherif A., Chabbi S., Anane N., Messaoud T., Gouider R., Belal S.
Neurobiol. Aging 36:2904.E09-2904.E11(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 THR-83.
Ref.132
"The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida."
Ravenscroft T.A., Pottier C., Murray M.E., Baker M., Christopher E., Levitch D., Brown P.H., Barker W., Duara R., Greig-Custo M., Betancourt A., English M., Sun X., Ertekin-Taner N., Graff-Radford N.R., Dickson D.W., Rademakers R.
Am. J. Neurodegener. Dis. 5:94-101(2016) [PubMed] [Europe PMC] [Abstract]
Ravenscroft T.A., Pottier C., Murray M.E., Baker M., Christopher E., Levitch D., Brown P.H., Barker W., Duara R., Greig-Custo M., Betancourt A., English M., Sun X., Ertekin-Taner N., Graff-Radford N.R., Dickson D.W., Rademakers R.
Am. J. Neurodegener. Dis. 5:94-101(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 ALA-206 AND VAL-378.
Ref.133
"Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease."
Tedde A., Bartoli A., Piaceri I., Ferrara S., Bagnoli S., Serio A., Sorbi S., Nacmias B.
Neurosci. Lett. 610:150-153(2016) [PubMed] [Europe PMC] [Abstract]
Tedde A., Bartoli A., Piaceri I., Ferrara S., Bagnoli S., Serio A., Sorbi S., Nacmias B.
Neurosci. Lett. 610:150-153(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 THR-408.
Ref.135
"Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase."
Sun L., Zhou R., Yang G., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 114:E476-E485(2017) [PubMed] [Europe PMC] [Abstract]
Sun L., Zhou R., Yang G., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 114:E476-E485(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AD3 GLN-35; VAL-79; LEU-82; PRO-85; LEU-89; SER-92; MET-94; PHE-96; LEU-97; HIS-115; ASN-116; ASP-120; LYS-120; ARG-134; ASP-135; VAL-139; THR-143; LEU-146; ILE-147; VAL-153; ASN-154; ARG-163; TYR-163; PRO-166; PRO-169; PHE-170; PRO-171; TRP-173; MET-174; LEU-177; PRO-178; VAL-183; ASP-184; ALA-206; SER-206; ARG-209; VAL-209; LEU-213; ARG-217; ARG-222; PHE-229; THR-231; LEU-233; THR-233; ARG-235; PRO-235; VAL-235; ILE-237; GLU-246; SER-250; VAL-260; PHE-261; PHE-262; ARG-263; LEU-264; SER-266; SER-267; GLY-269; VAL-271; ARG-274; VAL-275; ALA-280; GLY-280; ARG-282; VAL-285; VAL-286; ILE-354; GLN-358; GLU-378; VAL-378; VAL-381; ALA-384; ILE-390; VAL-392; VAL-394; THR-396; SER-405; THR-409; TYR-410; PHE-418; PRO-426; GLU-431; PHE-435; SER-436 AND VAL-439, CHARACTERIZATION OF VARIANT CMD1U GLY-333, MUTAGENESIS OF THR-99; PHE-105; ARG-108; LEU-113; PRO-117; GLU-123; HIS-131; ALA-136; ILE-143; LEU-150; TRP-165; ILE-168; PHE-176; GLU-184; ILE-202; SER-212; HIS-214; LEU-219; GLN-223; LEU-226; SER-230; ILE-238; LYS-239; THR-245; LEU-248; TYR-256; VAL-272; GLU-273; ARG-278; PRO-284; THR-291; ARG-352; SER-365; ARG-377; PHE-386; VAL-391; VAL-412; LEU-420; LEU-424; ALA-434 AND ILE-437.
Ref.136
"PSEN1 p.Thr116Ile variant in two Korean families with young onset Alzheimer's disease."
Bagyinszky E., Lee H.M., Van Giau V., Koh S.B., Jeong J.H., An S.S.A., Kim S.
Int. J. Mol. Sci. 19:0-0(2018) [PubMed] [Europe PMC] [Abstract]
Bagyinszky E., Lee H.M., Van Giau V., Koh S.B., Jeong J.H., An S.S.A., Kim S.
Int. J. Mol. Sci. 19:0-0(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ILE-116.
Ref.137
"Neuropathology and biochemistry of early onset familial Alzheimer's disease caused by presenilin-1 missense mutation Thr116Asn."
Sutovsky S., Smolek T., Turcani P., Petrovic R., Brandoburova P., Jadhav S., Novak P., Attems J., Zilka N.
J. Neural Transm. 125:965-976(2018) [PubMed] [Europe PMC] [Abstract]
Sutovsky S., Smolek T., Turcani P., Petrovic R., Brandoburova P., Jadhav S., Novak P., Attems J., Zilka N.
J. Neural Transm. 125:965-976(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ASN-116.
Ref.138
"Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation."
Wang J.C., Alinaghi S., Tafakhori A., Sikora E., Azcona L.J., Karkheiran S., Goate A., Paisan-Ruiz C., Darvish H.
Neurobiol. Aging 62:E15-E17(2018) [PubMed] [Europe PMC] [Abstract]
Wang J.C., Alinaghi S., Tafakhori A., Sikora E., Azcona L.J., Karkheiran S., Goate A., Paisan-Ruiz C., Darvish H.
Neurobiol. Aging 62:E15-E17(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AD3 PHE-142 AND ASP-206.
Ref.139
"Novel PSEN1 p.Gly417Ala mutation in a Korean patient with early-onset Alzheimer's disease with parkinsonism."
Giau V.V., Wang M.J., Bagyinszky E., Youn Y.C., An S.S.A., Kim S.
Neurobiol. Aging 72:E13-E17(2018) [PubMed] [Europe PMC] [Abstract]
Giau V.V., Wang M.J., Bagyinszky E., Youn Y.C., An S.S.A., Kim S.
Neurobiol. Aging 72:E13-E17(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 ALA-417.
Ref.140
"Phenotypic variability in autosomal dominant familial Alzheimer disease due to the S170F mutation of presenilin-1."
Tiedt H.O., Benjamin B., Niedeggen M., Lueschow A.
Neurodegener. Dis. 18:57-68(2018) [PubMed] [Europe PMC] [Abstract]
Tiedt H.O., Benjamin B., Niedeggen M., Lueschow A.
Neurodegener. Dis. 18:57-68(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AD3 PHE-170.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA familial early-onset form of Alzheimer disease. 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 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.
See also OMIM:607822| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_075260 | 35 | R → Q in AD3; unknown pathological significance; decreased protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006413 | 79 | A → V in AD3; also found in late-onset Alzheimer disease; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; no effect on interaction with GFAP. 7 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006414 | 82 | V → L in AD3; decreased protease activity with APP; no effect on interaction with GFAP. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075261 | 83 | I → T in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081228 | 85 | L → P in AD3; the patient also manifest spastic paraparesis and apraxia; loss of protease activity with APP in vitro; altered amyloid-beta production in cells transfected with the mutant and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081229 | 89 | V → L in AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_016214 | 92 | C → S in AD3; loss of protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081230 | 94 | V → M in AD3; unknown pathological significance; reduced protease activity with APP; no relevant change in amyloid-beta 42/amyloid-beta 40 ratio. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006415 | 96 | V → F in AD3; loss of protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081231 | 97 | V → L in AD3; unknown pathological significance; slightly reduced protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_009208 | 105 | F → L in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006416 | 115 | Y → C in AD3. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006417 | 115 | Y → H in AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081232 | 116 | T → I in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_010120 | 116 | T → N in AD3; unusual amyloid cotton wool plaques detected in one patient's brain; severe decrease of protease activity with APP; results in increased amyloid-beta 42/amyloid-beta 40 ratio. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_009209 | 117 | P → L in AD3; impaired ability to cleave Ephb2/CTF1; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; impaired regulation of neurite outgrowth. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081233 | 117 | P → S in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; impaired regulation of neurite outgrowth. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006418 | 120 | E → D in AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006419 | 120 | E → K in AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_070023 | 134 | L → R in AD3; uncertain pathological significance; loss of protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_010121 | 135 | N → D in AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006420 | 139 | M → I in AD3. Corresponds to variant dbSNP:rs63750522EnsemblClinVar. | 1 | |
| Natural variantiVAR_010122 | 139 | M → K in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006421 | 139 | M → T in AD3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006422 | 139 | M → V in AD3; increased amyloid-beta 42/amyloid-beta 40 ratio. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081234 | 142 | V → F in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006423 | 143 | I → F in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006424 | 143 | I → T in AD3; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 6 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006425 | 146 | M → I in AD3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006426 | 146 | M → L in AD3; disease phenotype shows high clinical variability; founder mutation originating from Southern Italy and distributed worldwide; alters the conformation of the active site; slightly increased protease activity with APP; decreased activity for Notch1 cleavage; no loss of its ability to cleave Ephb2/CTF1. 7 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006427 | 146 | M → V in AD3; loss of function as calcium-leak channel; results in calcium overload in the endoplasmic reticulum. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_010123 | 147 | T → I in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081235 | 153 | L → V in AD3; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081236 | 154 | Y → C in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081237 | 154 | Y → N in AD3; disease phenotype includes spastic paraparesis; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075262 | 156 | Y → FTY in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081238 | 159 | Y → F in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006428 | 163 | H → R in AD3; abolishes protease activity with APP; decreased activity for Notch cleavage. 9 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006429 | 163 | H → Y in AD3; slightly increased protease activity with APP and slightly increased amyloid-beta 42 production. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_010124 | 165 | W → C in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_016216 | 166 | L → P in AD3; onset in adolescence; severe decrease of protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; results in reduced Notch proteolysis. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081239 | 168 | Missing in AD3; unknown pathological significance; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006430 | 169 | S → L in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006431 | 169 | S → P in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081240 | 170 | S → F in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006432 | 171 | L → P in AD3; abolishes protease activity with APP. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_010125 | 173 | L → W in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_016217 | 174 | L → M in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075263 | 177 | F → L in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075264 | 177 | F → S in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075265 | 178 | S → P in AD3; unknown pathological significance; abolishes protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081241 | 183 | G → V in PIDB and AD3; neuropathologic examination of brain sections from the patient shows the presence of Pick bodies and absence of beta-amyloid plaques; unknown pathological significance; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio in vitro. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081242 | 184 | E → D in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_016218 | 206 | G → A in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081243 | 206 | G → D in AD3; affects APP processing resulting in increased amyloid-beta 42/amyloid-beta 40 ratio; does not affect NOTCH processing; does not affect endoproteolysis; reduced interaction with PEN2; results in decreased protein levels in the endoplasmic reticulum but increased levels in early endosome; reduced ability to maintain ER calcium homeostasis. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075266 | 206 | G → S in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075267 | 209 | G → E in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_009210 | 209 | G → R in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006433 | 209 | G → V in AD3; abolishes protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075268 | 213 | I → L in AD3; increases protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006434 | 213 | I → T in AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081244 | 217 | G → R in AD3; with unusual amyloid cotton wool plaques; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_010126 | 219 | L → P in AD3. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_075269 | 222 | Q → R in AD3; unknown pathological significance; slightly increased protease activity with APP and slightly increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081245 | 229 | I → F in AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006435 | 231 | A → T in AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006436 | 231 | A → V in AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_009211 | 233 | M → L in AD3; slightly decreased protease activity with APP resulting in altered amyloid-beta production and mildly increased amyloid-beta 42/amyloid-beta 40 ratio. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006437 | 233 | M → T in AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006438 | 235 | L → P in AD3; abolishes protease activity with APP. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081246 | 235 | L → R in AD3; abolishes protease activity with APP. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081247 | 235 | L → V in AD3; reduced APP cleavage resulting in decreased amyloid-beta 42 and amyloid-beta 40 production; no relevant change in amyloid-beta 42/amyloid-beta 40 ratio. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081248 | 237 | F → I in AD3; disease phenotype includes spastic paraparesis; unknown pathological significance; severe decrease of protease activity with APP; results in decreased amyloid-beta 42 and amyloid-beta 40 production. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_081249 | 237 | F → L in AD3; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006439 | 246 | A → E in AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; no loss of its ability to cleave Ephb2/CTF1. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006440 | 250 | L → S in AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_006441 | 260 | A → V in AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1. 5 Publications Manual assertion based on experiment ini
|