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Protein

Presenilin-1

Gene

PSEN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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).By similarity14 Publications

Sites

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

GO - Molecular functioni

  • aspartic endopeptidase activity, intramembrane cleaving Source: UniProtKB
  • aspartic-type endopeptidase activity Source: ARUK-UCL
  • 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

  • activation of MAPKK activity Source: Ensembl
  • amyloid-beta formation Source: UniProtKB
  • amyloid precursor protein catabolic process Source: HGNC
  • amyloid precursor protein metabolic process Source: UniProtKB
  • astrocyte activation Source: ARUK-UCL
  • astrocyte activation involved in immune response Source: ARUK-UCL
  • autophagosome assembly Source: Ensembl
  • blood vessel development Source: Ensembl
  • brain morphogenesis Source: Ensembl
  • Cajal-Retzius cell differentiation Source: Ensembl
  • canonical Wnt signaling pathway Source: GO_Central
  • cell-cell adhesion Source: MGI
  • cell fate specification Source: Ensembl
  • cellular response to amyloid-beta Source: ARUK-UCL
  • cellular response to DNA damage stimulus 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: MGI
  • 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-UCL
  • L-glutamate transport Source: Ensembl
  • membrane protein ectodomain proteolysis Source: HGNC
  • memory Source: ARUK-UCL
  • mitochondrial transport Source: Ensembl
  • modulation of age-related behavioral decline Source: ARUK-UCL
  • myeloid dendritic cell differentiation Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of apoptotic signaling pathway Source: Ensembl
  • negative regulation of axonogenesis Source: Ensembl
  • negative regulation of core promoter binding Source: CAFA
  • negative regulation of epidermal growth factor-activated receptor activity Source: Ensembl
  • negative regulation of neuron apoptotic process Source: Ensembl
  • negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: CAFA
  • 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-UCL
  • neutrophil degranulation Source: Reactome
  • Notch receptor processing Source: HGNC
  • Notch signaling pathway Source: UniProtKB-KW
  • positive regulation of amyloid fibril formation Source: ARUK-UCL
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of catalytic activity Source: HGNC
  • positive regulation of coagulation Source: Ensembl
  • positive regulation of dendritic spine development Source: CACAO
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
  • positive regulation of protein binding Source: ARUK-UCL
  • positive regulation of protein import into nucleus, translocation Source: CAFA
  • positive regulation of receptor recycling Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: CACAO
  • post-embryonic development Source: Ensembl
  • protein glycosylation Source: Ensembl
  • protein processing Source: HGNC
  • protein transport Source: Ensembl
  • regulation of canonical Wnt signaling pathway Source: UniProtKB
  • regulation of phosphorylation Source: UniProtKB
  • 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_Central
  • somitogenesis Source: Ensembl
  • synapse organization Source: ARUK-UCL
  • 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

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1251985. Nuclear signaling by ERBB4.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-1980148. Signaling by NOTCH3.
R-HSA-1980150. Signaling by NOTCH4.
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.
SignaLinkiP49768.
SIGNORiP49768.

Protein family/group databases

MEROPSiA22.001.
TCDBi1.A.54.1.1. the presenilin er ca(2+) leak channel (presenilin) family.

Names & Taxonomyi

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:
Gene namesi
Name:PSEN1
Synonyms:AD3, PS1, PSNL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000080815.18.
HGNCiHGNC:9508. PSEN1.

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
Topological domaini1 – 82Cytoplasmic1 PublicationAdd BLAST82
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

Pathology & Biotechi

Involvement in diseasei

Alzheimer disease 3 (AD3)40 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
Natural variantiVAR_07526035R → Q in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750592Ensembl.1
Natural variantiVAR_00641379A → V in AD3; unknown pathological significance; no effect on interaction with GFAP. 4 PublicationsCorresponds to variant dbSNP:rs63749824Ensembl.1
Natural variantiVAR_00641482V → L in AD3; no effect on interaction with GFAP. 3 PublicationsCorresponds to variant dbSNP:rs63749967Ensembl.1
Natural variantiVAR_07526183I → T in AD3. 1 Publication1
Natural variantiVAR_01621492C → S in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751141Ensembl.1
Natural variantiVAR_00641596V → F in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750601Ensembl.1
Natural variantiVAR_009208105F → L in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750321Ensembl.1
Natural variantiVAR_006416115Y → C in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750450Ensembl.1
Natural variantiVAR_006417115Y → H in AD3. 2 Publications1
Natural variantiVAR_010120116T → N in AD3. 2 Publications1
Natural variantiVAR_009209117P → L in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749805Ensembl.1
Natural variantiVAR_006418120E → D in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751272Ensembl.1
Natural variantiVAR_006419120E → K in AD3. Corresponds to variant dbSNP:rs63750800Ensembl.1
Natural variantiVAR_070023134L → R in AD3; uncertain pathological significance. 1 Publication1
Natural variantiVAR_010121135N → D in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750353Ensembl.1
Natural variantiVAR_006420139M → I in AD3. Corresponds to variant dbSNP:rs63750522Ensembl.1
Natural variantiVAR_010122139M → K in AD3. 1 Publication1
Natural variantiVAR_006421139M → T in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751106Ensembl.1
Natural variantiVAR_006422139M → V in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751037Ensembl.1
Natural variantiVAR_006423143I → F in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750322Ensembl.1
Natural variantiVAR_006424143I → T in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750004Ensembl.1
Natural variantiVAR_006425146M → I in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750391Ensembl.1
Natural variantiVAR_006426146M → L in AD3. 3 PublicationsCorresponds to variant dbSNP:rs63750306Ensembl.1
Natural variantiVAR_006427146M → V in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750306Ensembl.1
Natural variantiVAR_010123147T → I in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750907Ensembl.1
Natural variantiVAR_075262156Y → FTY in AD3; unknown pathological significance. 1 Publication1
Natural variantiVAR_006428163H → R in AD3. 7 PublicationsCorresponds to variant dbSNP:rs63750590Ensembl.1
Natural variantiVAR_006429163H → Y in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749885Ensembl.1
Natural variantiVAR_010124165W → C in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751484Ensembl.1
Natural variantiVAR_016216166L → P in AD3; onset in adolescence. 1 PublicationCorresponds to variant dbSNP:rs63750265Ensembl.1
Natural variantiVAR_006430169S → L in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751210Ensembl.1
Natural variantiVAR_006431169S → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750418Ensembl.1
Natural variantiVAR_006432171L → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750963Ensembl.1
Natural variantiVAR_010125173L → W in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750299Ensembl.1
Natural variantiVAR_016217174L → M in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751144Ensembl.1
Natural variantiVAR_075263177F → L in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749911Ensembl.1
Natural variantiVAR_075264177F → S in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749806Ensembl.1
Natural variantiVAR_075265178S → P in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750155Ensembl.1
Natural variantiVAR_016218206G → A in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750082Ensembl.1
Natural variantiVAR_075266206G → S in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750569Ensembl.1
Natural variantiVAR_075267209G → E in AD3; unknown pathological significance. 1 Publication1
Natural variantiVAR_009210209G → R in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749880Ensembl.1
Natural variantiVAR_006433209G → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750053Ensembl.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:rs63751309Ensembl.1
Natural variantiVAR_010126219L → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750761Ensembl.1
Natural variantiVAR_075269222Q → R in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750009Ensembl.1
Natural variantiVAR_006435231A → T in AD3. 3 PublicationsCorresponds to variant dbSNP:rs63749836Ensembl.1
Natural variantiVAR_006436231A → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750799Ensembl.1
Natural variantiVAR_009211233M → L in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751287Ensembl.1
Natural variantiVAR_006437233M → T in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751024Ensembl.1
Natural variantiVAR_006438235L → P in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63749835Ensembl.1
Natural variantiVAR_006439246A → E in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750526Ensembl.1
Natural variantiVAR_006440250L → S in AD3. Corresponds to variant dbSNP:rs63751163Ensembl.1
Natural variantiVAR_006441260A → V in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63751420Ensembl.1
Natural variantiVAR_075270261V → F in AD3; unknown pathological significance; nearly abolishes protease activity with APP. 2 PublicationsCorresponds to variant dbSNP:rs63750964Ensembl.1
Natural variantiVAR_006442262L → F in AD3. Corresponds to variant dbSNP:rs63750248Ensembl.1
Natural variantiVAR_070025262L → V in AD3. 1 Publication1
Natural variantiVAR_006443263C → R in AD3. Corresponds to variant dbSNP:rs63750543Ensembl.1
Natural variantiVAR_006444264P → L in AD3. 3 PublicationsCorresponds to variant dbSNP:rs63750301Ensembl.1
Natural variantiVAR_016219266G → S in AD3. 1 PublicationCorresponds to variant dbSNP:rs121917807Ensembl.1
Natural variantiVAR_006445267P → S in AD3. Corresponds to variant dbSNP:rs63751229Ensembl.1
Natural variantiVAR_006446267P → T in AD3. 1 Publication1
Natural variantiVAR_006447269R → G in AD3. Corresponds to variant dbSNP:rs63751019Ensembl.1
Natural variantiVAR_006448269R → H in AD3. Corresponds to variant dbSNP:rs63750900Ensembl.1
Natural variantiVAR_016220271L → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750886Ensembl.1
Natural variantiVAR_075271274T → R in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750284Ensembl.1
Natural variantiVAR_006449278R → T in AD3. 1 PublicationCorresponds to variant dbSNP:rs63749891Ensembl.1
Natural variantiVAR_006450280E → A in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750231Ensembl.1
Natural variantiVAR_006451280E → G in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750231Ensembl.1
Natural variantiVAR_009212282L → R in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750050Ensembl.1
Natural variantiVAR_006452285A → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751139Ensembl.1
Natural variantiVAR_006453286L → V in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751235Ensembl.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:rs63751164Ensembl.1
Natural variantiVAR_075274358R → Q in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751174Ensembl.1
Natural variantiVAR_075275365S → Y in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750941Ensembl.1
Natural variantiVAR_006455378G → E in AD3. 1 Publication1
Natural variantiVAR_006456384G → A in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750646Ensembl.1
Natural variantiVAR_010128390S → I in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750883Ensembl.1
Natural variantiVAR_006457392L → V in AD3. 3 PublicationsCorresponds to variant dbSNP:rs63751416Ensembl.1
Natural variantiVAR_075276394G → V in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750929Ensembl.1
Natural variantiVAR_070026396A → T in AD3; uncertain pathological significance. 1
Natural variantiVAR_010129405N → S in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751254Ensembl.1
Natural variantiVAR_075277408I → T in AD3. 1 Publication1
Natural variantiVAR_009213409A → T in AD3. 1 PublicationCorresponds to variant dbSNP:rs63750227Ensembl.1
Natural variantiVAR_006458410C → Y in AD3. 3 PublicationsCorresponds to variant dbSNP:rs661Ensembl.1
Natural variantiVAR_075278418L → F in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751316Ensembl.1
Natural variantiVAR_006459426A → P in AD3. 1 PublicationCorresponds to variant dbSNP:rs63751223Ensembl.1
Natural variantiVAR_025605431A → E in AD3. 2 PublicationsCorresponds to variant dbSNP:rs63750083Ensembl.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:rs63750001Ensembl.1
Natural variantiVAR_006460436P → Q in AD3; partially abolishes gamma-secretase activity. 2 PublicationsCorresponds to variant dbSNP:rs28930977Ensembl.1
Natural variantiVAR_008141436P → S in AD3; partially abolishes gamma-secretase activity. 2 PublicationsCorresponds to variant dbSNP:rs63749925Ensembl.1
Natural variantiVAR_075282439I → V in AD3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750249Ensembl.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:rs121917809Ensembl.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
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: 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