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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>

<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). 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).By similarity15 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 sitei2573 Publications1
Active sitei3853 Publications1

<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
  • aspartic-type endopeptidase activity Source: Reactome
  • beta-catenin binding Source: UniProtKB
  • cadherin binding Source: GO_Central
  • calcium channel activity Source: UniProtKB
  • endopeptidase activity Source: MGI
  • PDZ domain binding Source: UniProtKB

GO - Biological processi

<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 functionHydrolase, Protease
Biological processApoptosis, Cell adhesion, Notch signaling pathway

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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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

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SignaLinki
P49768

SIGNOR Signaling Network Open Resource

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SIGNORi
P49768

Protein family/group databases

MEROPS protease database

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MEROPSi
A22.001

Transport Classification Database

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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 Publications)
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>OrganismiHomo 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 identifieri9606 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<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
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 14

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000080815.18

Human Gene Nomenclature Database

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HGNCi
HGNC:9508 PSEN1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
104311 gene

neXtProt; the human protein knowledge platform

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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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 domaini1 – 82Cytoplasmic1 PublicationAdd BLAST82
<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>Transmembranei83 – 103Helical1 PublicationAdd BLAST21
Topological domaini104 – 132Lumenal1 PublicationAdd BLAST29
Transmembranei133 – 153Helical1 PublicationAdd BLAST21
Topological domaini154 – 166Cytoplasmic1 PublicationAdd BLAST13
Transmembranei167 – 189Helical1 PublicationAdd BLAST23
Topological domaini190 – 194Lumenal1 Publication5
Transmembranei195 – 216Helical1 PublicationAdd BLAST22
Topological domaini217 – 220Cytoplasmic1 Publication4
Transmembranei221 – 241Helical1 PublicationAdd BLAST21
Topological domaini242 – 248Lumenal1 Publication7
Transmembranei249 – 272Helical1 PublicationAdd BLAST24
Topological domaini273 – 380Cytoplasmic1 PublicationAdd BLAST108
Transmembranei381 – 401Helical1 PublicationAdd BLAST21
Topological domaini402 – 407Lumenal1 Publication6
Transmembranei408 – 428Helical1 PublicationAdd BLAST21
Topological domaini429 – 432Cytoplasmic1 Publication4
Transmembranei433 – 453Helical1 PublicationAdd BLAST21
Topological domaini454 – 467Lumenal1 PublicationAdd BLAST14

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, 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)41 Publications
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 keyPosition(s)DescriptionActionsGraphical viewLength
<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_07526035R → Q in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750592EnsemblClinVar.1
Natural variantiVAR_00641379A → V in AD3; unknown pathological significance; no effect on interaction with GFAP. 4 PublicationsCorresponds to variant dbSNP:rs63749824EnsemblClinVar.1
Natural variantiVAR_00641482V → L in AD3; no effect on interaction with GFAP. 3 PublicationsCorresponds to variant dbSNP:rs63749967EnsemblClinVar.1
Natural variantiVAR_07526183I → T in AD3. 1 Publication1
Natural variantiVAR_01621492C → S in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751141EnsemblClinVar.1
Natural variantiVAR_00641596V → F in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750601EnsemblClinVar.1
Natural variantiVAR_009208105F → L in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750321EnsemblClinVar.1
Natural variantiVAR_006416115Y → C in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750450EnsemblClinVar.1
Natural variantiVAR_006417115Y → H in AD3. 2 Publications1
Natural variantiVAR_010120116T → N in AD3. 2 Publications1
Natural variantiVAR_009209117P → L in AD3; impaired ability to cleave Ephb2/CTF1. 2 PublicationsCorresponds to variant dbSNP:rs63749805EnsemblClinVar.1
Natural variantiVAR_006418120E → D in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751272EnsemblClinVar.1
Natural variantiVAR_006419120E → K in AD3. Corresponds to variant dbSNP:rs63750800EnsemblClinVar.1
Natural variantiVAR_070023134L → R in AD3; uncertain pathological significance. 1 Publication1
Natural variantiVAR_010121135N → D in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750353EnsemblClinVar.1
Natural variantiVAR_006420139M → I in AD3. Corresponds to variant dbSNP:rs63750522EnsemblClinVar.1
Natural variantiVAR_010122139M → K in AD3. 1 Publication1
Natural variantiVAR_006421139M → T in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751106EnsemblClinVar.1
Natural variantiVAR_006422139M → V in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751037EnsemblClinVar.1
Natural variantiVAR_006423143I → F in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750322EnsemblClinVar.1
Natural variantiVAR_006424143I → T in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750004EnsemblClinVar.1
Natural variantiVAR_006425146M → I in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750391EnsemblClinVar.1
Natural variantiVAR_006426146M → L in AD3; no loss of its ability to cleave Ephb2/CTF1. 4 PublicationsCorresponds to variant dbSNP:rs63750306EnsemblClinVar.1
Natural variantiVAR_006427146M → V in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750306EnsemblClinVar.1
Natural variantiVAR_010123147T → I in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750907EnsemblClinVar.1
Natural variantiVAR_075262156Y → FTY in AD3; unknown pathological significance. 1 Publication1
Natural variantiVAR_006428163H → R in AD3. 7 PublicationsCorresponds to variant dbSNP:rs63750590EnsemblClinVar.1
Natural variantiVAR_006429163H → Y in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749885EnsemblClinVar.1
Natural variantiVAR_010124165W → C in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751484EnsemblClinVar.1
Natural variantiVAR_016216166L → P in AD3; onset in adolescence. 1 PublicationCorresponds to variant dbSNP:rs63750265EnsemblClinVar.1
Natural variantiVAR_006430169S → L in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751210EnsemblClinVar.1
Natural variantiVAR_006431169S → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750418EnsemblClinVar.1
Natural variantiVAR_006432171L → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750963EnsemblClinVar.1
Natural variantiVAR_010125173L → W in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750299EnsemblClinVar.1
Natural variantiVAR_016217174L → M in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751144EnsemblClinVar.1
Natural variantiVAR_075263177F → L in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749911EnsemblClinVar.1
Natural variantiVAR_075264177F → S in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749806EnsemblClinVar.1
Natural variantiVAR_075265178S → P in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750155EnsemblClinVar.1
Natural variantiVAR_016218206G → A in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750082EnsemblClinVar.1
Natural variantiVAR_075266206G → S in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750569EnsemblClinVar.1
Natural variantiVAR_075267209G → E in AD3; unknown pathological significance. 1 Publication1
Natural variantiVAR_009210209G → R in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749880EnsemblClinVar.1
Natural variantiVAR_006433209G → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750053EnsemblClinVar.1
Natural variantiVAR_075268213I → L in AD3; unknown pathological significance; increases protease activity with APP. 2 PublicationsCorresponds to variant dbSNP:rs63750861Ensembl.1
Natural variantiVAR_006434213I → T in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751309EnsemblClinVar.1
Natural variantiVAR_010126219L → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750761EnsemblClinVar.1
Natural variantiVAR_075269222Q → R in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750009EnsemblClinVar.1
Natural variantiVAR_006435231A → T in AD3. 3 PublicationsCorresponds to variant dbSNP:rs63749836EnsemblClinVar.1
Natural variantiVAR_006436231A → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750799EnsemblClinVar.1
Natural variantiVAR_009211233M → L in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751287EnsemblClinVar.1
Natural variantiVAR_006437233M → T in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751024EnsemblClinVar.1
Natural variantiVAR_006438235L → P in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63749835EnsemblClinVar.1
Natural variantiVAR_006439246A → E in AD3; no loss of its ability to cleave Ephb2/CTF1. 2 PublicationsCorresponds to variant dbSNP:rs63750526EnsemblClinVar.1
Natural variantiVAR_006440250L → S in AD3. Corresponds to variant dbSNP:rs63751163EnsemblClinVar.1
Natural variantiVAR_006441260A → V in AD3; impaired ability to cleave Ephb2/CTF1. 3 PublicationsCorresponds to variant dbSNP:rs63751420EnsemblClinVar.1
Natural variantiVAR_075270261V → F in AD3; unknown pathological significance; nearly abolishes protease activity with APP. 2 PublicationsCorresponds to variant dbSNP:rs63750964EnsemblClinVar.1
Natural variantiVAR_006442262L → F in AD3. Corresponds to variant dbSNP:rs63750248EnsemblClinVar.1
Natural variantiVAR_070025262L → V in AD3. 1 Publication1
Natural variantiVAR_006443263C → R in AD3. Corresponds to variant dbSNP:rs63750543EnsemblClinVar.1
Natural variantiVAR_006444264P → L in AD3; impaired ability to cleave Ephb2/CTF1. 4 PublicationsCorresponds to variant dbSNP:rs63750301EnsemblClinVar.1
Natural variantiVAR_016219266G → S in AD3. 1 PublicationCorresponds to variant dbSNP:rs121917807EnsemblClinVar.1
Natural variantiVAR_006445267P → S in AD3. Corresponds to variant dbSNP:rs63751229EnsemblClinVar.1
Natural variantiVAR_006446267P → T in AD3. 1 Publication1
Natural variantiVAR_006447269R → G in AD3. Corresponds to variant dbSNP:rs63751019EnsemblClinVar.1
Natural variantiVAR_006448269R → H in AD3. Corresponds to variant dbSNP:rs63750900EnsemblClinVar.1
Natural variantiVAR_016220271L → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750886EnsemblClinVar.1
Natural variantiVAR_075271274T → R in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750284EnsemblClinVar.1
Natural variantiVAR_006449278R → T in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749891EnsemblClinVar.1
Natural variantiVAR_006450280E → A in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750231EnsemblClinVar.1
Natural variantiVAR_006451280E → G in AD3; impaired ability to cleave Ephb2/CTF1. 2 PublicationsCorresponds to variant dbSNP:rs63750231EnsemblClinVar.1
Natural variantiVAR_009212282L → R in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750050EnsemblClinVar.1
Natural variantiVAR_006452285A → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751139EnsemblClinVar.1
Natural variantiVAR_006453286L → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751235EnsemblClinVar.1
Natural variantiVAR_010127289S → C in AD3. 1
Natural variantiVAR_075272352R → RR in AD3; unknown pathological significance. 1 Publication1
Natural variantiVAR_075273354T → I in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751164EnsemblClinVar.1
Natural variantiVAR_075274358R → Q in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751174EnsemblClinVar.1
Natural variantiVAR_075275365S → Y in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750941EnsemblClinVar.1
Natural variantiVAR_006455378G → E in AD3. 1 Publication1
Natural variantiVAR_006456384G → A in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750646EnsemblClinVar.1
Natural variantiVAR_010128390S → I in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750883EnsemblClinVar.1
Natural variantiVAR_006457392L → V in AD3. 3 PublicationsCorresponds to variant dbSNP:rs63751416EnsemblClinVar.1
Natural variantiVAR_075276394G → V in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750929EnsemblClinVar.1
Natural variantiVAR_070026396A → T in AD3; uncertain pathological significance. 1
Natural variantiVAR_010129405N → S in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751254EnsemblClinVar.1
Natural variantiVAR_075277408I → T in AD3. 1 PublicationCorresponds to variant dbSNP:rs906454643Ensembl.1
Natural variantiVAR_009213409A → T in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750227EnsemblClinVar.1
Natural variantiVAR_006458410C → Y in AD3. 3 PublicationsCorresponds to variant dbSNP:rs661EnsemblClinVar.1
Natural variantiVAR_075278418L → F in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751316EnsemblClinVar.1
Natural variantiVAR_006459426A → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751223EnsemblClinVar.1
Natural variantiVAR_025605431A → E in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750083EnsemblClinVar.1
Natural variantiVAR_075280435L → F in AD3; no endoproteolytic cleavage; no APP nor NOTCH1 processing; no detectable amyloid-beta; almost abolishes gamma-secretase activity. 3 PublicationsCorresponds to variant dbSNP:rs63750001EnsemblClinVar.1
Natural variantiVAR_006460436P → Q in AD3; partially abolishes gamma-secretase activity. 2 PublicationsCorresponds to variant dbSNP:rs121917808EnsemblClinVar.1
Natural variantiVAR_008141436P → S in AD3; partially abolishes gamma-secretase activity. 2 PublicationsCorresponds to variant dbSNP:rs63749925EnsemblClinVar.1
Natural variantiVAR_075282439I → V in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750249EnsemblClinVar.1
Frontotemporal dementia (FTD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons.
See also OMIM:600274
Cardiomyopathy, dilated 1U (CMD1U)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:613694
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064902333D → G in CMD1U. 1 PublicationCorresponds to variant dbSNP:rs121917809EnsemblClinVar.1
Acne inversa, familial, 3 (ACNINV3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.
See also OMIM:613737

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi66 – 72Missing : No effect on interaction with GFAP. 1 Publication7
Mutagenesisi76 – 77KY → AA: No effect on interaction with GFAP. 1 Publication2
Mutagenesisi82 – 83VI → EE: Loss of interaction with GFAP. 1 Publication2
Mutagenesisi82V → K or E: Loss of interaction with GFAP. 1 Publication1
Mutagenesisi84 – 85ML → EE: Loss of interaction with GFAP. 1 Publication2
Mutagenesisi202I → F: Nearly abolishes protease activity with APP. 1 Publication1
Mutagenesisi226L → F: Increases protease activity with APP. 1 Publication1
Mutagenesisi237F → I: Abolishes protease activity with APP. 1 Publication1
Mutagenesisi248L → R: Nearly abolishes protease activity with APP. 1 Publication1
Mutagenesisi256Y → F: Alters gamma-secretase cleavage specificity. Increased production of amyloid-beta protein 42. No effect on enzymatic activity. 1 Publication1
Mutagenesisi257D → A: Impaired ability to cleave Ephb2/CTF1. 1 Publication1
Mutagenesisi257D → A: Loss of endoproteolytic cleavage; reduces production of amyloid-beta in APP processing and of NICD in NOTCH1 processing. 3 Publications1
Mutagenesisi257D → E: Abolishes gamma-secretase activity. Reduces production of amyloid-beta in APP processing. Accumulation of full-length PS1. Loss of binding of transition state analog gamma-secretase inhibitor. 3 Publications1
Mutagenesisi286L → A, E, P, Q, R or W: Increases production of amyloid-beta in APP processing. 1 Publication1
Mutagenesisi286L → E or R: Reduces production of NICD in NOTCH1 processing. 1 Publication1
Mutagenesisi292M → D: Loss of endoproteolytic cleavage. 1 Publication1
Mutagenesisi310S → A: Abolishes PKA-mediated phosphorylation; no effect on caspase-mediated cleavage. 1 Publication1
Mutagenesisi345D → N: Abolishes caspase cleavage. 1 Publication1
Mutagenesisi346S → A: Abolishes PKC-mediated phosphorylation; no effect on PKA-mediated phosphorylation. 1 Publication1
Mutagenesisi346S → E: Inhibits caspase-mediated cleavage. Modulates progression of apoptosis. 1 Publication1
Mutagenesisi373D → N: No effect on caspase cleavage. 1 Publication1
Mutagenesisi385D → A: Loss of endoproteolytic cleavage. Reduces production of amyloid-beta in APP processing. Disassembly of the N-cadherin/PS1 complex at the cell surface. Impairs CDH2 processing. 5 Publications1
Mutagenesisi385D → E: Abolishes gamma-secretase activity. Reduces production of amyloid-beta in APP processing. Accumulation of full-length PS1. Loss of binding of transition state analog gamma-secretase inhibitor. 5 Publications1
Mutagenesisi385D → N: No effect on caspase cleavage. 5 Publications1
Mutagenesisi389Y → F: Alters gamma-secretase cleavage specificity. Increased production of amyloid-beta protein 42. No effect on enzymatic activity. 1 Publication1
Mutagenesisi424L → V: Increases protease activity with APP. 1 Publication1
Mutagenesisi433P → A: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Slightly increased amyloid-beta protein 42/40 ratio. 1 Publication1
Mutagenesisi433P → D, F, L, N or V: No endoproteolytic cleavage; no APP, nor NOTCH1 processing. No detectable amyloid-beta. 1 Publication1
Mutagenesisi433P → G: Very little endoproteolysis. Little APP processing. No NOTCH1 processing. Very low levels amyloid-beta protein 40 and no detectable amyloid-beta protein 42. 1 Publication1
Mutagenesisi434A → C: Some loss of endoproteolytic cleavage. Some loss of APP and NOTCH1 processing. Six-fold increase in amyloid-beta protein 42/40 ratio. 1 Publication1
Mutagenesisi434A → D, I, L or V: No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable amyloid-beta. 1 Publication1
Mutagenesisi434A → G: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Reduced amyloid-beta protein 42/40 ratio. 1 Publication1
Mutagenesisi435L → A: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Greatly reduced amyloid-beta protein 42/40 ratio. 1 Publication1
Mutagenesisi435L → G: Greatly reduced endoproteolytic cleavage. Very little APP and NOTCH1 processing. Very low levels of amyloid-beta protein 40 and no detectable amyloid-beta protein 42. 1 Publication1
Mutagenesisi435L → I: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. 1 Publication1
Mutagenesisi435L → V: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Some increase in amyloid-beta protein 42/40 ratio. 1 Publication1

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Cardiomyopathy, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNET

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DisGeNETi
5663

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
PSEN1

MalaCards human disease database

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MalaCardsi
PSEN1
MIMi600274 phenotype
607822 phenotype
613694 phenotype
613737 phenotype

Open Targets

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OpenTargetsi
ENSG00000080815

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
275864 Behavioral variant of frontotemporal dementia
1020 Early-onset autosomal dominant Alzheimer disease
154 Familial isolated dilated cardiomyopathy
387 NON RARE IN EUROPE: Hidradenitis suppurativa
100070 Progressive non-fluent aphasia
100069 Semantic dementia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA33855

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2473

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2402

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
PSEN1

Domain mapping of disease mutations (DMDM)

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DMDMi
1709856

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000255911 – 298Presenilin-1 NTF subunitAdd BLAST298
ChainiPRO_0000025592299 – 467Presenilin-1 CTF subunitAdd BLAST169
ChainiPRO_0000236055346 – 467Presenilin-1 CTF12Add BLAST122

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei43PhosphoserineCombined sources1
Modified residuei51PhosphoserineBy similarity1
Modified residuei310Phosphoserine; by PKA1 Publication1
Modified residuei346Phosphoserine; by PKC1 Publication1
Modified residuei367PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by caspase-3 to produce the fragment, PS1-CTF12.4 Publications
After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei291 – 292Cleavage; alternate1 Publication2
Sitei292 – 293Cleavage; alternate1 Publication2
Sitei298 – 299Cleavage1 Publication2
Sitei345 – 346Cleavage; by caspase1 Publication2

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P49768

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P49768

MaxQB - The MaxQuant DataBase

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MaxQBi
P49768