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P49768 (PSN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 175. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Presenilin-1

Short name=PS-1
EC=3.4.23.-
Alternative name(s):
Protein S182

Cleaved into the following 3 chains:

  1. Presenilin-1 NTF subunit
  2. Presenilin-1 CTF subunit
  3. Presenilin-1 CTF12
    Short name=PS1-CTF12
Gene names
Name:PSEN1
Synonyms:AD3, PS1, PSNL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable 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 (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis. Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.36 Ref.39

Subunit structure

Homodimer. Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity. Other components which are associated with the complex include SLC25A64, SLC5A7, PHB and PSEN1 isoform 3. Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment. Associates with proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Associates with NOTCH1. Associates with cadherin/catenin adhesion complexes through direct binding to CDH1 or CDH2. Interaction with CDH1 stabilizes the complex and stimulates cell-cell aggregation. Interaction with CDH2 is essential for trafficking of CDH2 from the endoplasmic reticulum to the plasma membrane. Interacts with CTNND2, CTNNB1, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with isoform 3 of GFAP. Interacts with DOCK3 By similarity. Ref.17 Ref.18 Ref.20 Ref.22 Ref.26 Ref.28 Ref.29 Ref.30 Ref.37

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cell surface. Note: Bound to NOTCH1 also at the cell surface. Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane. Also present in azurophil granules of neutrophils. Ref.13 Ref.17 Ref.27 Ref.30

Tissue specificity

Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes. Ref.13 Ref.27

Domain

The PAL motif is required for normal active site conformation.

Post-translational modification

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. Ref.14 Ref.16

After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis. Ref.15 Ref.34

Involvement in disease

Alzheimer disease 3 (AD3) [MIM:607822]: A 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 constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.29 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63 Ref.64 Ref.66 Ref.67 Ref.68 Ref.69 Ref.70 Ref.71 Ref.72 Ref.73 Ref.74 Ref.75 Ref.77 Ref.78 Ref.79 Ref.80 Ref.81 Ref.82 Ref.86

Frontotemporal dementia (FTD) [MIM:600274]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Cardiomyopathy, dilated 1U (CMD1U) [MIM:613694]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.83

Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.46

Sequence similarities

Belongs to the peptidase A22A family.

Ontologies

Keywords
   Biological processApoptosis
Cell adhesion
Notch signaling pathway
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAlzheimer disease
Amyloidosis
Cardiomyopathy
Disease mutation
Neurodegeneration
   DomainTransmembrane
Transmembrane helix
   Molecular functionHydrolase
Protease
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processCajal-Retzius cell differentiation

Inferred from electronic annotation. Source: Ensembl

L-glutamate transport

Inferred from electronic annotation. Source: Ensembl

Notch receptor processing

Traceable author statement Ref.12. Source: HGNC

Notch signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

T cell activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

T cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

activation of MAPKK activity

Inferred from electronic annotation. Source: Ensembl

amyloid precursor protein catabolic process

Traceable author statement Ref.12. Source: HGNC

anagen

Inferred from electronic annotation. Source: Ensembl

autophagic vacuole assembly

Inferred from electronic annotation. Source: Ensembl

beta-amyloid formation

Inferred from electronic annotation. Source: Ensembl

beta-amyloid metabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

blood vessel development

Inferred from electronic annotation. Source: Ensembl

brain morphogenesis

Inferred from electronic annotation. Source: Ensembl

calcium ion transmembrane transport

Inferred from mutant phenotype PubMed 16959576. Source: GOC

calcium ion transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell fate specification

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

cerebral cortex cell migration

Inferred from electronic annotation. Source: Ensembl

choline transport

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral neural tube patterning

Inferred from electronic annotation. Source: Ensembl

embryonic limb morphogenesis

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum calcium ion homeostasis

Inferred from genetic interaction PubMed 16959576. Source: UniProtKB

epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

heart looping

Inferred from electronic annotation. Source: Ensembl

hematopoietic progenitor cell differentiation

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

membrane protein ectodomain proteolysis

Inferred from direct assay Ref.12. Source: HGNC

memory

Inferred from electronic annotation. Source: Ensembl

mitochondrial transport

Inferred from electronic annotation. Source: Ensembl

myeloid leukocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from direct assay PubMed 10805794. Source: UniProtKB

negative regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of axonogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of epidermal growth factor-activated receptor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of ubiquitin-protein transferase activity

Inferred from electronic annotation. Source: Ensembl

neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron development

Inferred from electronic annotation. Source: Ensembl

neuron migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of catalytic activity

Inferred from direct assay Ref.12. Source: HGNC

positive regulation of coagulation

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of receptor recycling

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

protein glycosylation

Inferred from electronic annotation. Source: Ensembl

protein processing

Inferred from direct assay Ref.12. Source: HGNC

protein transport

Inferred from electronic annotation. Source: Ensembl

regulation of phosphorylation

Inferred from direct assay PubMed 9689133. Source: UniProtKB

regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

regulation of resting membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

single organismal cell-cell adhesion

Inferred from mutant phenotype PubMed 11953314. Source: MGI

skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

skin morphogenesis

Inferred from electronic annotation. Source: Ensembl

smooth endoplasmic reticulum calcium ion homeostasis

Inferred from Biological aspect of Ancestor. Source: RefGenome

somitogenesis

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle targeting

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 9632714. Source: UniProtKB

Golgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Z disc

Inferred from Biological aspect of Ancestor. Source: RefGenome

apical plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

axon

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell cortex

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell surface

Inferred from Biological aspect of Ancestor. Source: RefGenome

centrosome

Inferred from direct assay PubMed 9298903. Source: UniProtKB

ciliary rootlet

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

dendritic shaft

Inferred from Biological aspect of Ancestor. Source: RefGenome

endoplasmic reticulum

Inferred from direct assay Ref.12. Source: HGNC

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

gamma-secretase complex

Inferred from direct assay PubMed 10801983. Source: UniProtKB

growth cone

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Traceable author statement Ref.1. Source: UniProtKB

integral component of plasma membrane

Inferred from direct assay Ref.12. Source: HGNC

kinetochore

Inferred from direct assay PubMed 9298903. Source: UniProtKB

lysosomal membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane

Inferred from direct assay PubMed 22375059. Source: MGI

membrane raft

Inferred from direct assay PubMed 20299451. Source: UniProt

mitochondrial inner membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitochondrion

Inferred from direct assay PubMed 12377771. Source: UniProtKB

neuromuscular junction

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

nuclear membrane

Inferred from direct assay PubMed 9298903. Source: UniProtKB

nuclear outer membrane

Inferred from direct assay PubMed 9246482. Source: MGI

perinuclear region of cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

rough endoplasmic reticulum

Inferred from direct assay PubMed 9632714. Source: UniProtKB

smooth endoplasmic reticulum

Inferred from direct assay PubMed 9632714. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from physical interaction Ref.20. Source: UniProtKB

aspartic-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

beta-catenin binding

Inferred from physical interaction PubMed 9632714. Source: UniProtKB

cadherin binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

calcium channel activity

Inferred from mutant phenotype PubMed 16959576. Source: UniProtKB

endopeptidase activity

Inferred from direct assay PubMed 8755489. Source: MGI

protein binding

Inferred from physical interaction PubMed 22036569. Source: IntAct

Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49768-1)

Also known as: I-467;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P49768-2)

Also known as: I-463;

The sequence of this isoform differs from the canonical sequence as follows:
     26-29: Missing.
Isoform 3 (identifier: P49768-3)

Also known as: I-374;

The sequence of this isoform differs from the canonical sequence as follows:
     26-29: Missing.
     319-467: STERESQDTV...DQLAFHQFYI → RACLPPAAIN...RNGKPRGTVI
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 4 (identifier: P49768-4)

Also known as: Minilin;

The sequence of this isoform differs from the canonical sequence as follows:
     162-184: IHAWLIISSLLLLFFFSFIYLGE → SMRHRSLLSTLFFLWLGILVTVT
     185-467: Missing.
Isoform 5 (identifier: P49768-5)

The sequence of this isoform differs from the canonical sequence as follows:
     319-467: STERESQDTV...DQLAFHQFYI → RACLPPAAIN...RNGKPRGTVI
Isoform 6 (identifier: P49768-6)

The sequence of this isoform differs from the canonical sequence as follows:
     319-376: Missing.
Isoform 7 (identifier: P49768-7)

The sequence of this isoform differs from the canonical sequence as follows:
     257-289: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 298298Presenilin-1 NTF subunit
PRO_0000025591
Chain299 – 467169Presenilin-1 CTF subunit
PRO_0000025592
Chain346 – 467122Presenilin-1 CTF12
PRO_0000236055

Regions

Topological domain1 – 8282Cytoplasmic Potential
Transmembrane83 – 10321Helical; Potential
Topological domain104 – 13229Lumenal Potential
Transmembrane133 – 15321Helical; Potential
Topological domain154 – 1607Cytoplasmic Potential
Transmembrane161 – 18121Helical; Potential
Topological domain182 – 1909Lumenal Potential
Transmembrane191 – 21121Helical; Potential
Topological domain212 – 2209Cytoplasmic Potential
Transmembrane221 – 24121Helical; Potential
Topological domain242 – 2432Lumenal Potential
Transmembrane244 – 26421Helical; Potential
Topological domain265 – 380116Cytoplasmic Potential
Transmembrane381 – 40121Helical; Potential
Topological domain402 – 4076Lumenal Potential
Transmembrane408 – 42821Helical; Potential
Topological domain429 – 4324Cytoplasmic Potential
Intramembrane433 – 45321Helical; Potential
Topological domain454 – 46714Cytoplasmic Potential
Region322 – 450129Required for interaction with CTNNB1
Region372 – 39928Required for interaction with CTNND2
Region464 – 4674Interaction with MTCH1
Motif433 – 4353PAL
Compositional bias94 – 974Poly-Val
Compositional bias171 – 1744Poly-Leu
Compositional bias418 – 4258Poly-Leu

Sites

Active site2571 Probable
Active site3851 Probable
Site291 – 2922Cleavage; alternate
Site292 – 2932Cleavage; alternate
Site298 – 2992Cleavage
Site345 – 3462Cleavage; by caspase

Amino acid modifications

Modified residue431Phosphoserine Ref.38 Ref.47
Modified residue3101Phosphoserine; by PKA Ref.34
Modified residue3461Phosphoserine; by PKC Ref.34
Modified residue3671Phosphoserine Ref.47

Natural variations

Alternative sequence26 – 294Missing in isoform 2 and isoform 3.
VSP_005191
Alternative sequence162 – 18423IHAWL…IYLGE → SMRHRSLLSTLFFLWLGILV TVT in isoform 4.
VSP_007986
Alternative sequence185 – 467283Missing in isoform 4.
VSP_007987
Alternative sequence257 – 28933Missing in isoform 7.
VSP_041440
Alternative sequence319 – 467149STERE…HQFYI → RACLPPAAINLLSIAPMAPR LFMPKGACRPTAQKGSHKTL LQRMMMAGSVRNGKPRGTVI in isoform 3 and isoform 5.
VSP_005192
Alternative sequence319 – 37658Missing in isoform 6.
VSP_012288
Natural variant791A → V in AD3; no effect on interaction with GFAP. Ref.29 Ref.59 Ref.73
VAR_006413
Natural variant821V → L in AD3; no effect on interaction with GFAP. Ref.29 Ref.49 Ref.66
VAR_006414
Natural variant921C → S in AD3. Ref.75
VAR_016214
Natural variant961V → F in AD3. Ref.52
VAR_006415
Natural variant1051F → L in AD3. Ref.73
VAR_009208
Natural variant1131L → P in frontotemporal dementia. Ref.76
VAR_016215
Natural variant1151Y → C in AD3. Ref.59
VAR_006416
Natural variant1151Y → H in AD3. Ref.49 Ref.66
VAR_006417
Natural variant1161T → N in AD3. Ref.72
VAR_010120
Natural variant1171P → L in AD3. Ref.63
VAR_009209
Natural variant1201E → D in AD3. Ref.60 Ref.66
VAR_006418
Natural variant1201E → K in AD3.
VAR_006419
Natural variant1341L → R in AD3; uncertain pathological significance. Ref.86
VAR_070023
Natural variant1351N → D in AD3. Ref.53
VAR_010121
Natural variant1391M → I in AD3.
VAR_006420
Natural variant1391M → K in AD3. Ref.62
VAR_010122
Natural variant1391M → T in AD3. Ref.49 Ref.66
VAR_006421
Natural variant1391M → V in AD3. Ref.51 Ref.73
VAR_006422
Natural variant1431I → F in AD3. Ref.67
VAR_006423
Natural variant1431I → T in AD3. Ref.48
VAR_006424
Natural variant1461M → I in AD3.
VAR_006425
Natural variant1461M → L in AD3. Ref.1 Ref.66
VAR_006426
Natural variant1461M → V in AD3. Ref.51
VAR_006427
Natural variant1471T → I in AD3. Ref.66
VAR_010123
Natural variant1631H → R in AD3. Ref.1 Ref.49 Ref.52 Ref.60 Ref.66 Ref.86
VAR_006428
Natural variant1631H → Y in AD3. Ref.51
VAR_006429
Natural variant1651W → C in AD3. Ref.66
VAR_010124
Natural variant1661L → P in AD3; onset in adolescence. Ref.80
VAR_016216
Natural variant1691S → L in AD3. Ref.64
VAR_006430
Natural variant1691S → P in AD3. Ref.70
VAR_006431
Natural variant1711L → P in AD3. Ref.56
VAR_006432
Natural variant1731L → W in AD3. Ref.66
VAR_010125
Natural variant1741L → M in AD3. Ref.81
VAR_016217
Natural variant2051F → L.
Corresponds to variant rs1042864 [ dbSNP | Ensembl ].
VAR_011876
Natural variant2061G → A in AD3. Ref.78
VAR_016218
Natural variant2091G → R in AD3. Ref.68
VAR_009210
Natural variant2091G → V in AD3. Ref.60
VAR_006433
Natural variant2131I → T in AD3. Ref.52
VAR_006434
Natural variant2141H → Y Probable disease-associated mutation found in a patient with dementia. Ref.86
VAR_070024
Natural variant2191L → P in AD3. Ref.71
VAR_010126
Natural variant2311A → T in AD3. Ref.49 Ref.66
VAR_006435
Natural variant2311A → V in AD3. Ref.59
VAR_006436
Natural variant2331M → L in AD3. Ref.69
VAR_009211
Natural variant2331M → T in AD3. Ref.55 Ref.66
VAR_006437
Natural variant2351L → P in A3D. Ref.66
VAR_006438
Natural variant2461A → E in AD3. Ref.1
VAR_006439
Natural variant2501L → S in AD3.
VAR_006440
Natural variant2601A → V in AD3. Ref.50 Ref.60
VAR_006441
Natural variant2621L → F in AD3.
VAR_006442
Natural variant2621L → V in AD3. Ref.86
VAR_070025
Natural variant2631C → R in AD3.
VAR_006443
Natural variant2641P → L in AD3. Ref.49 Ref.60 Ref.66
VAR_006444
Natural variant2661G → S in AD3. Ref.79
VAR_016219
Natural variant2671P → S in AD3.
VAR_006445
Natural variant2671P → T in AD3. Ref.51
VAR_006446
Natural variant2691R → G in AD3.
VAR_006447
Natural variant2691R → H in AD3.
VAR_006448
Natural variant2711L → V in AD3. Ref.82
VAR_016220
Natural variant2781R → T in AD3. Ref.55
VAR_006449
Natural variant2801E → A in AD3. Ref.51 Ref.54
VAR_006450
Natural variant2801E → G in AD3. Ref.51
VAR_006451
Natural variant2821L → R in AD3. Ref.69
VAR_009212
Natural variant2851A → V in AD3. Ref.50
VAR_006452
Natural variant2861L → V in AD3. Ref.1
VAR_006453
Natural variant2891S → C in AD3.
VAR_010127
Natural variant3151Y → C Found in a renal cell carcinoma sample; somatic mutation. Ref.85
VAR_064747
Natural variant3181E → G. Ref.57 Ref.58 Ref.59 Ref.65 Ref.66 Ref.69 Ref.73 Ref.84
Corresponds to variant rs17125721 [ dbSNP | Ensembl ].
VAR_006454
Natural variant3331D → G in CMD1U. Ref.83
VAR_064902
Natural variant3781G → E in AD3. Ref.61
VAR_006455
Natural variant3841G → A in AD3. Ref.48
VAR_006456
Natural variant3901S → I in AD3. Ref.66
VAR_010128
Natural variant3921L → V in AD3. Ref.49 Ref.50 Ref.66
VAR_006457
Natural variant3961A → T in AD3; uncertain pathological significance.
VAR_070026
Natural variant4051N → S in AD3. Ref.74
VAR_010129
Natural variant4091A → T in AD3. Ref.69
VAR_009213
Natural variant4101C → Y in AD3. Ref.49 Ref.60 Ref.66
Corresponds to variant rs661 [ dbSNP | Ensembl ].
VAR_006458
Natural variant4261A → P in AD3. Ref.60
VAR_006459
Natural variant4311A → E in AD3. Ref.77
VAR_025605
Natural variant4361P → Q in AD3. Ref.64
Corresponds to variant rs28930977 [ dbSNP | Ensembl ].
VAR_006460
Natural variant4361P → S in AD3. Ref.67
VAR_008141

Experimental info

Mutagenesis66 – 727Missing: No effect on interaction with GFAP. Ref.29
Mutagenesis76 – 772KY → AA: No effect on interaction with GFAP.
Mutagenesis82 – 832VI → EE: Loss of interaction with GFAP. Ref.29
Mutagenesis821V → K or E: Loss of interaction with GFAP. Ref.29
Mutagenesis84 – 852ML → EE: Loss of interaction with GFAP.
Mutagenesis2561Y → F: Alters gamma-secretase cleavage specificity. Increased production of amyloid beta(42). No effect on enzymatic activity. Ref.36
Mutagenesis2571D → A: Loss of endoproteolytic cleavage; reduces production of amyloid beta in APP processing and of NICD in NOTCH1 processing. Ref.23 Ref.24 Ref.36
Mutagenesis2571D → 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. Ref.23 Ref.24 Ref.36
Mutagenesis2861L → A, E, P, Q, R or W: Increases production of amyloid beta in APP processing. Ref.25
Mutagenesis2861L → E or R: Reduces production of NICD in NOTCH1 processing. Ref.25
Mutagenesis2921M → D: Loss of endoproteolytic cleavage. Ref.19
Mutagenesis3101S → A: Abolishes PKA-mediated phosphorylation; no effect on caspase-mediated cleavage. Ref.34
Mutagenesis3451D → N: Abolishes caspase cleavage. Ref.16
Mutagenesis3461S → A: Abolishes PKC-mediated phosphorylation; no effect on PKA-mediated phosphorylation. Ref.34
Mutagenesis3461S → E: Inhibits caspase-mediated cleavage. Modulates progression of apoptosis. Ref.34
Mutagenesis3731D → N: No effect on caspase cleavage. Ref.16
Mutagenesis3851D → 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. Ref.16 Ref.23 Ref.24 Ref.30 Ref.36
Mutagenesis3851D → 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. Ref.16 Ref.23 Ref.24 Ref.30 Ref.36
Mutagenesis3851D → N: No effect on caspase cleavage. Ref.16 Ref.23 Ref.24 Ref.30 Ref.36
Mutagenesis3891Y → F: Alters gamma-secretase cleavage specificity. Increased production of amyloid beta(42). No effect on enzymatic activity. Ref.36
Mutagenesis4331P → A: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Slightly increased Abeta42/Abeta40 ratio. Ref.39
Mutagenesis4331P → D, F, L, N or V: No endoproteolytic cleavage; no APP nor NOTCH1 processing. No detectable Abetano detectable Abeta. Ref.39
Mutagenesis4331P → G: Very little endoproteolysis. Little APP processing. No NOTCH1 processing. Very low levels Abeta40 and no detectable Abeta42. Ref.39
Mutagenesis4341A → C: Some loss of endoproteolytic cleavage. Some loss of APP and NOTCH1 processing. Six-fold increase in Abeta42/Abeta40 ratio. Ref.39
Mutagenesis4341A → D, I, L or V: No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable Abeta. Ref.39
Mutagenesis4341A → G: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Reduced Abeta42/Abeta40 ratio. Ref.39
Mutagenesis4351L → A: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Greatly reduced Abeta42/Abeta40 ratio. Ref.39
Mutagenesis4351L → F: No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable Abeta. Ref.39
Mutagenesis4351L → G: Greatly reduced endoproteolytic cleavage. Very little APP and NOTCH1 processing. Very low levels of Abeta40 and no detectable Abeta42. Ref.39
Mutagenesis4351L → I: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Ref.39
Mutagenesis4351L → V: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Some increase in Abeta42/Abeta40 ratio. Ref.39
Sequence conflict1281R → G in AAL16811. Ref.7

Secondary structure

.................... 467
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (I-467) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 5E0F451EF82BCF20

FASTA46752,668
        10         20         30         40         50         60 
MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNRERQEHND RRSLGHPEPL SNGRPQGNSR 

        70         80         90        100        110        120 
QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE 

       130        140        150        160        170        180 
DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI 

       190        200        210        220        230        240 
YLGEVFKTYN VAVDYITVAL LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY 

       250        260        270        280        290        300 
LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE 

       310        320        330        340        350        360 
GDPEAQRRVS KNSKYNAEST ERESQDTVAE NDDGGFSEEW EAQRDSHLGP HRSTPESRAA 

       370        380        390        400        410        420 
VQELSSSILA GEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL 

       430        440        450        460 
TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI 

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Isoform 2 (I-463) [UniParc].

Checksum: 955325791A81470F
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FASTA46352,197
Isoform 3 (I-374) [UniParc].

Checksum: 5172C076410745BF
Show »

FASTA37442,287
Isoform 4 (Minilin) [UniParc].

Checksum: 95C68A7EA0020874
Show »

FASTA18421,073
Isoform 5 [UniParc].

Checksum: A09D682EC6F568FD
Show »

FASTA37842,757
Isoform 6 [UniParc].

Checksum: 4855BDDCCD1D7D71
Show »

FASTA40946,328
Isoform 7 [UniParc].

Checksum: C3930DB665C32929
Show »

FASTA43448,997

References

« Hide 'large scale' references
[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. expand/collapse author list , 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: Brain.
[2]"Identification and characterization of presenilin I-467, I-463 and I-374."
Sahara N., Yahagi Y., Takagi H., Kondo T., Okochi M., Usami M., Shirasawa T., Mori H.
FEBS Lett. 381:7-11(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
Tissue: Blood and Brain.
[3]"Human presenilin 1 gene encodes an alternative protein-minilin."
Powell C.S., Gegg M.E., Palmer M.S.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[4]"Complete sequence of the gene for presenilin 1."
Rowen L., Madan A., Qin S., Abbasi N., Dors M., Ratcliffe A., Madan A., Dickhoff R., Shaffer T., James R., Lasky S., Hood L.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]Kang L., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Tongue.
[7]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Skin.
[10]"Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential expression in oogenesis and embryogenesis."
Tsujimura A., Yasojima K., Hashimoto-Gotoh T.
Biochem. Biophys. Res. Commun. 231:392-396(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-113.
[11]"Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant."
Vidal R., Ghiso J., Wisniewski T., Frangione B.
FEBS Lett. 393:19-23(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 24-32, ALTERNATIVE SPLICING (ISOFORMS 6 AND 7).
Tissue: Megakaryocyte and Platelet.
[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]
Cited for: PROTEIN SEQUENCE OF 36-42; 61-76; 109-129; 217-239; 270-278; 315-320; 345-352 AND 381-395 (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, CHARACTERIZATION OF GAMMA-SECRETASE COMPLEX.
[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.
[14]"Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue."
Podlisny M.B., Citron M., Amarante P., Sherrington R., Xia W., Zhang J., Diehl T., Levesque G., Fraser P., Haass C., Koo E.H., Seubert P., St George-Hyslop P.H., Teplow D.B., Selkoe D.J.
Neurobiol. Dis. 3:325-337(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[15]"Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C."
Walter J., Gruenberg J., Capell A., Pesold B., Schindzielorz A., Citron M., Mendla K., St George-Hyslop P.H., Multhaup G., Selkoe D.J., Haass C.
Proc. Natl. Acad. Sci. U.S.A. 94:5349-5354(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[16]"Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family."
Gruenberg J., Walter J., Loetscher H., Deuschle U., Jacobsen H., Haass C.
Biochemistry 37:2263-2270(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CASPASE CLEAVAGE SITE, MUTAGENESIS OF ASP-345; ASP-373 AND ASP-385.
[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: INTERACTION WITH CTNNB1, SUBCELLULAR LOCATION.
[18]"Interaction of presenilins with the filamin family of actin-binding proteins."
Zhang W., Han S.W., McKeel D.W., Goate A., Wu J.Y.
J. Neurosci. 18:914-922(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FLNA AND FLNB.
[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.
[20]"Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1."
Xu X., Shi Y.-C., Wu X., Gambetti P., Sui D., Cui M.-Z.
J. Biol. Chem. 274:32543-32546(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MTCH1.
[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.
[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.
[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, MUTAGENESIS OF ASP-257 AND ASP-385.
[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, MUTAGENESIS OF ASP-257 AND ASP-385.
[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, MUTAGENESIS OF LEU-286.
[26]"Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex."
Baki L., Marambaud P., Efthimiopoulos S., Georgakopoulos A., Wen P., Cui W., Shioi J., Koo E., Ozawa M., Friedrich V.L., Robakis N.K.
Proc. Natl. Acad. Sci. U.S.A. 98:2381-2386(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CDH1.
[27]"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.
[28]"Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein."
Sai X., Kawamura Y., Kokame K., Yamaguchi H., Shiraishi H., Suzuki R., Suzuki T., Kawaichi M., Miyata T., Kitamura T., De Strooper B., Yanagisawa K., Komano H.
J. Biol. Chem. 277:12915-12920(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HERPUD1.
[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.
[30]"Presenilin 1 is involved in maturation and trafficking of N-cadherin to the plasma membrane."
Uemura K., Kitagawa N., Kohno R., Kuzuya A., Kageyama T., Chonabayashi K., Shibasaki H., Shimohama S.
J. Neurosci. Res. 74:184-191(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDH2, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-385.
[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.
[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.
[33]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[34]"Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis."
Fluhrer R., Friedlein A., Haass C., Walter J.
J. Biol. Chem. 279:1585-1593(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-310 AND SER-346, MUTAGENESIS OF SER-310 AND SER-346.
[35]"Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins."
Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., Martoglio B.
J. Biol. Chem. 279:50790-50798(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY.
[36]"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.
[37]"Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability."
Serban G., Kouchi Z., Baki L., Georgakopoulos A., Litterst C.M., Shioi J., Robakis N.K.
J. Biol. Chem. 280:36007-36012(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDH1 AND CTNNB1.
[38]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[39]"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.
[40]"The presenilin genes: a new gene family involved in Alzheimer disease pathology."
Cruts M., Hendriks L., Van Broeckhoven C.
Hum. Mol. Genet. 5:1449-1455(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[41]"Presenilin mutations in Alzheimer's disease."
Cruts M., van Broeckhoven C.
Hum. Mutat. 11:183-190(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[42]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[43]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[44]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[45]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[46]"Gamma-secretase gene mutations in familial acne inversa."
Wang B., Yang W., Wen W., Sun J., Su B., Liu B., Ma D., Lv D., Wen Y., Qu T., Chen M., Sun M., Shen Y., Zhang X.
Science 330:1065-1065(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ACNINV3.
[47]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43 AND SER-367, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[48]"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.
[49]"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. expand/collapse author list , 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.
[50]"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. expand/collapse author list , 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.
[51]"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. expand/collapse author list , 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.
[52]"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.
[53]"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.
[54]"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.
[55]"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.
[56]"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.
[57]"The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease."
Mattila K.M., Forsell C., Pirttila T., Rinne J.O., Lehtimaki T., Roytta M., Lilius L., Eerola A., St George-Hyslop P.H., Frey H., Lannfelt L.
Ann. Neurol. 44:965-967(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-318.
[58]"Missense mutation E318G of the presenilin-1 gene appears to be a nonpathogenic polymorphism."
Aldudo J., Bullido M.J., Frank A., Valdivieso F.
Ann. Neurol. 44:985-986(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-318.
[59]"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.
[60]"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.
[61]"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.
[62]"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.
[63]"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.
[64]"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.
[65]"The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer disease."
Dermaut B., Cruts M., Slooter A.J.C., van Gestel S., de Jonghe C., Vanderstichele H., Vanmechelen E., Breteler M.M., Hofman A., van Duijn C.M., van Broeckhoven C.
Am. J. Hum. Genet. 64:290-292(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-318.
[66]"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.
[67]"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.
[68]"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.
[69]"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.
[70]"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.
[71]"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.
[72]"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.
[73]"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.
[74]"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.
[75]"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.
[76]"Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation."
Raux G., Gantier R., Thomas-Anterion C., Boulliat J., Verpillat P., Hannequin D., Brice A., Frebourg T., Campion D.
Neurology 55:1577-1578(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FRONTOTEMPORAL DEMENTIA PRO-113.
[77]Erratum
Ringman J.M., Jain V., Murrell J., Ghetti B., Cochran E.J.
Hum. Genet. 109:242-242(2001)
Cited for: VARIANT AD3 GLU-431.
[78]"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. expand/collapse author list , 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.
[79]"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.
[80]"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.
[81]"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.
[82]"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.
[83]"Mutations of presenilin genes in dilated cardiomyopathy and heart failure."
Li D., Parks S.B., Kushner J.D., Nauman D., Burgess D., Ludwigsen S., Partain J., Nixon R.R., Allen C.N., Irwin R.P., Jakobs P.M., Litt M., Hershberger R.E.
Am. J. Hum. Genet. 79:1030-1039(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD1U GLY-333.
[84]"Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome."
Cornier A.S., Staehling-Hampton K., Delventhal K.M., Saga Y., Caubet J.-F., Sasaki N., Ellard S., Young E., Ramirez N., Carlo S.E., Torres J., Emans J.B., Turnpenny P.D., Pourquie O.
Am. J. Hum. Genet. 82:1334-1341(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-318.
[85]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYS-315.
[86]"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.
+Additional computationally mapped references.

Web resources

Alzheimer Research Forum

Presenilins mutations

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L42110 mRNA. Translation: AAB46416.1.
L76517 mRNA. Translation: AAB46370.1.
L76528 expand/collapse EMBL AC list , L76519, L76520, L76521, L76522, L76523, L76524, L76525, L76526, L76527 Genomic DNA. Translation: AAB46371.1.
U40379 mRNA. Translation: AAB05894.1.
U40380 mRNA. Translation: AAB05895.1.
AJ008005 mRNA. Translation: CAA07825.1.
AF109907 Genomic DNA. Translation: AAC97960.1.
AF416717 mRNA. Translation: AAL16811.1.
AK312531 mRNA. Translation: BAG35430.1.
AC004858 Genomic DNA. Translation: AAF19253.1.
AC004858 Genomic DNA. Translation: AAF19254.1.
CH471061 Genomic DNA. Translation: EAW81092.1.
BC011729 mRNA. Translation: AAH11729.1.
D84149 Genomic DNA. Translation: BAA20883.1.
CCDSCCDS9812.1. [P49768-1]
CCDS9813.1. [P49768-2]
PIRS58396.
S63683.
S63684.
RefSeqNP_000012.1. NM_000021.3. [P49768-1]
NP_015557.2. NM_007318.2. [P49768-2]
XP_005267921.1. XM_005267864.1. [P49768-1]
XP_005267923.1. XM_005267866.1. [P49768-2]
UniGeneHs.3260.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KR6NMR-A292-467[»]
ProteinModelPortalP49768.
SMRP49768. Positions 292-467.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111642. 77 interactions.
DIPDIP-1134N.
IntActP49768. 41 interactions.
MINTMINT-88325.
STRING9606.ENSP00000326366.

Chemistry

BindingDBP49768.
ChEMBLCHEMBL2094135.
GuidetoPHARMACOLOGY2402.

Protein family/group databases

MEROPSA22.001.
TCDB1.A.54.1.1. the presenilin er ca(2+) leak channel (presenilin) family.

PTM databases

PhosphoSiteP49768.

Polymorphism databases

DMDM1709856.

Proteomic databases

MaxQBP49768.
PaxDbP49768.
PRIDEP49768.

Protocols and materials databases

DNASU5663.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261970; ENSP00000261970; ENSG00000080815. [P49768-6]
ENST00000324501; ENSP00000326366; ENSG00000080815. [P49768-1]
ENST00000344094; ENSP00000339523; ENSG00000080815. [P49768-5]
ENST00000357710; ENSP00000350342; ENSG00000080815. [P49768-2]
ENST00000394157; ENSP00000377712; ENSG00000080815. [P49768-4]
ENST00000394164; ENSP00000377719; ENSG00000080815. [P49768-2]
ENST00000553855; ENSP00000452242; ENSG00000080815. [P49768-5]
ENST00000555386; ENSP00000450845; ENSG00000080815. [P49768-3]
ENST00000557511; ENSP00000451429; ENSG00000080815. [P49768-6]
GeneID5663.
KEGGhsa:5663.
UCSCuc001xnq.4. human. [P49768-4]
uc001xnr.3. human. [P49768-1]
uc001xnv.3. human. [P49768-2]

Organism-specific databases

CTD5663.
GeneCardsGC14P073603.
GeneReviewsPSEN1.
HGNCHGNC:9508. PSEN1.
HPACAB006844.
HPA030760.
MIM104311. gene.
600274. phenotype.
607822. phenotype.
613694. phenotype.
613737. phenotype.
neXtProtNX_P49768.
Orphanet275864. Behavioral variant of frontotemporal dementia.
1020. Early-onset autosomal dominant Alzheimer disease.
154. Familial isolated dilated cardiomyopathy.
387. Hidradenitis suppurativa.
100070. Progressive non-fluent aphasia.
100069. Semantic dementia.
PharmGKBPA33855.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG237920.
HOVERGENHBG011375.
InParanoidP49768.
KOK04505.
OMAEARDHEI.
PhylomeDBP49768.
TreeFamTF315040.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
SignaLinkP49768.

Gene expression databases

ArrayExpressP49768.
BgeeP49768.
CleanExHS_PSEN1.
GenevestigatorP49768.

Family and domain databases

InterProIPR002031. Pept_A22A_PS1.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERPTHR10202. PTHR10202. 1 hit.
PTHR10202:SF7. PTHR10202:SF7. 1 hit.
PfamPF01080. Presenilin. 1 hit.
[Graphical view]
PRINTSPR01072. PRESENILIN.
PR01073. PRESENILIN1.
SMARTSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPSEN1. human.
EvolutionaryTraceP49768.
GeneWikiPSEN1.
GenomeRNAi5663.
NextBio22006.
PMAP-CutDBP49768.
PROP49768.
SOURCESearch...

Entry information

Entry namePSN1_HUMAN
AccessionPrimary (citable) accession number: P49768
Secondary accession number(s): B2R6D3 expand/collapse secondary AC list , O95465, Q14762, Q15719, Q15720, Q96P33, Q9UIF0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM