P49768 (PSN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 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 Familial acne inversa 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 process	Apoptosis Cell adhesion Notch signaling pathway
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Alzheimer disease Amyloidosis Cardiomyopathy Disease mutation Neurodegeneration
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Cajal-Retzius cell differentiation Inferred from electronic annotation. Source: Compara L-glutamate transport Inferred from electronic annotation. Source: Compara Notch receptor processing Traceable author statement Ref.12. Source: HGNC Notch signaling pathway Traceable author statement. Source: Reactome T cell activation involved in immune response Inferred from electronic annotation. Source: Compara T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara activation of MAPKK activity Inferred from electronic annotation. Source: Compara amyloid precursor protein catabolic process Traceable author statement Ref.12. Source: HGNC anagen Inferred from electronic annotation. Source: Compara apoptotic process Traceable author statement. Source: Reactome autophagic vacuole assembly Inferred from electronic annotation. Source: Compara beta-amyloid metabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome blood vessel development Inferred from electronic annotation. Source: Compara brain morphogenesis Inferred from electronic annotation. Source: Compara cell fate specification Inferred from electronic annotation. Source: Compara cell-cell adhesion Inferred from mutant phenotype PubMed 11953314. Source: MGI cerebral cortex cell migration Inferred from electronic annotation. Source: Compara choline transport Inferred from electronic annotation. Source: Compara dorsal/ventral neural tube patterning Inferred from electronic annotation. Source: Compara embryonic limb morphogenesis Inferred from electronic annotation. Source: Compara epithelial cell proliferation Inferred from electronic annotation. Source: Compara heart looping Inferred from electronic annotation. Source: Compara hematopoietic progenitor cell differentiation Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro membrane protein ectodomain proteolysis Inferred from direct assay Ref.12. Source: HGNC membrane protein intracellular domain proteolysis Traceable author statement. Source: Reactome memory Inferred from electronic annotation. Source: Compara mitochondrial transport Inferred from electronic annotation. Source: Compara myeloid leukocyte differentiation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from direct assay PubMed 10805794. Source: UniProtKB negative regulation of axonogenesis Inferred from electronic annotation. Source: Compara negative regulation of epidermal growth factor-activated receptor activity Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome neuron apoptotic process Inferred from electronic annotation. Source: Compara neuron development Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of catalytic activity Inferred from direct assay Ref.12. Source: HGNC positive regulation of coagulation Inferred from electronic annotation. Source: Compara positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of receptor recycling Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara protein glycosylation Inferred from electronic annotation. Source: Compara protein processing Inferred from direct assay Ref.12. Source: HGNC protein transport Inferred from electronic annotation. Source: Compara regulation of phosphorylation Inferred from direct assay PubMed 9689133. Source: UniProtKB regulation of protein binding Inferred from electronic annotation. Source: Compara regulation of resting membrane potential Inferred from electronic annotation. Source: Compara regulation of synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara response to DNA damage stimulus Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from electronic annotation. Source: Compara skeletal system morphogenesis Inferred from electronic annotation. Source: Compara skin morphogenesis Inferred from electronic annotation. Source: Compara smooth endoplasmic reticulum calcium ion homeostasis Inferred from Biological aspect of Ancestor. Source: RefGenome somitogenesis Inferred from electronic annotation. Source: Compara synaptic vesicle targeting Inferred from electronic annotation. Source: Compara thymus development Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi 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: Compara dendritic shaft Inferred from Biological aspect of Ancestor. Source: RefGenome 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 to 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 raft Inferred from Biological aspect of Ancestor. Source: RefGenome mitochondrial inner membrane Inferred from Biological aspect of Ancestor. Source: RefGenome neuromuscular junction Inferred from Biological aspect of Ancestor. Source: RefGenome neuronal cell body Inferred from Biological aspect of Ancestor. Source: RefGenome 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_function	aspartic-type endopeptidase activity Inferred from electronic annotation. Source: InterPro 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	6	EBI-297277,EBI-77613
Arc	Q63053	3	EBI-2606326,EBI-5275794	From a different organism.
CDC37	Q16543	3	EBI-297277,EBI-295634
CTNNB1	P35222	2	EBI-297277,EBI-491549
ECSIT	Q9BQ95	4	EBI-297277,EBI-712452
JUP	P14923	4	EBI-297277,EBI-702484
ST13	P50502	3	EBI-297277,EBI-357285
TMED10	P49755	3	EBI-297277,EBI-998422

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 298

298

Presenilin-1 NTF subunit

PRO_0000025591

Chain

299 – 467

169

Presenilin-1 CTF subunit

PRO_0000025592

Chain

346 – 467

122

Presenilin-1 CTF12

PRO_0000236055

Regions

Topological domain

1 – 82

82

Cytoplasmic Potential

Transmembrane

83 – 103

21

Helical; Potential

Topological domain

104 – 132

29

Lumenal Potential

Transmembrane

133 – 153

21

Helical; Potential

Topological domain

154 – 160

7

Cytoplasmic Potential

Transmembrane

161 – 181

21

Helical; Potential

Topological domain

182 – 190

9

Lumenal Potential

Transmembrane

191 – 211

21

Helical; Potential

Topological domain

212 – 220

9

Cytoplasmic Potential

Transmembrane

221 – 241

21

Helical; Potential

Topological domain

242 – 243

2

Lumenal Potential

Transmembrane

244 – 264

21

Helical; Potential

Topological domain

265 – 380

116

Cytoplasmic Potential

Transmembrane

381 – 401

21

Helical; Potential

Topological domain

402 – 407

6

Lumenal Potential

Transmembrane

408 – 428

21

Helical; Potential

Topological domain

429 – 432

4

Cytoplasmic Potential

Intramembrane

433 – 453

21

Helical; Potential

Topological domain

454 – 467

14

Cytoplasmic Potential

Region

322 – 450

129

Required for interaction with CTNNB1

Region

372 – 399

28

Required for interaction with CTNND2

Region

464 – 467

4

Interaction with MTCH1

Motif

433 – 435

3

PAL

Compositional bias

94 – 97

4

Poly-Val

Compositional bias

171 – 174

4

Poly-Leu

Compositional bias

418 – 425

8

Poly-Leu

Sites

Active site

257

1

Probable

Active site

385

1

Probable

Site

291 – 292

2

Cleavage; alternate

Site

292 – 293

2

Cleavage; alternate

Site

298 – 299

2

Cleavage

Site

345 – 346

2

Cleavage; by caspase

Amino acid modifications

Modified residue

43

1

Phosphoserine Ref.38 Ref.47

Modified residue

310

1

Phosphoserine; by PKA Ref.34

Modified residue

346

1

Phosphoserine; by PKC Ref.34

Modified residue

365

1

Phosphoserine By similarity

Modified residue

367

1

Phosphoserine Ref.47

Natural variations

Alternative sequence

26 – 29

4

Missing in isoform 2 and isoform 3.

VSP_005191

Alternative sequence

162 – 184

23

IHAWL…IYLGE → SMRHRSLLSTLFFLWLGILV TVT in isoform 4.

VSP_007986

Alternative sequence

185 – 467

283

Missing in isoform 4.

VSP_007987

Alternative sequence

257 – 289

33

Missing in isoform 7.

VSP_041440

Alternative sequence

319 – 467

149

STERE…HQFYI → RACLPPAAINLLSIAPMAPR LFMPKGACRPTAQKGSHKTL LQRMMMAGSVRNGKPRGTVI in isoform 3 and isoform 5.

VSP_005192

Alternative sequence

319 – 376

58

Missing in isoform 6.

VSP_012288

Natural variant

79

1

A → V in AD3; no effect on interaction with GFAP. Ref.29 Ref.59 Ref.73

VAR_006413

Natural variant

82

1

V → L in AD3; no effect on interaction with GFAP. Ref.29 Ref.49 Ref.66

VAR_006414

Natural variant

92

1

C → S in AD3. Ref.75

VAR_016214

Natural variant

96

1

V → F in AD3. Ref.52

VAR_006415

Natural variant

105

1

F → L in AD3. Ref.73

VAR_009208

Natural variant

113

1

L → P in frontotemporal dementia. Ref.76

VAR_016215

Natural variant

115

1

Y → C in AD3. Ref.59

VAR_006416

Natural variant

115

1

Y → H in AD3. Ref.49 Ref.66

VAR_006417

Natural variant

116

1

T → N in AD3. Ref.72

VAR_010120

Natural variant

117

1

P → L in AD3. Ref.63

VAR_009209

Natural variant

120

1

E → D in AD3. Ref.60 Ref.66

VAR_006418

Natural variant

120

1

E → K in AD3.

VAR_006419

Natural variant

135

1

N → D in AD3. Ref.53

VAR_010121

Natural variant

139

1

M → I in AD3.

VAR_006420

Natural variant

139

1

M → K in AD3. Ref.62

VAR_010122

Natural variant

139

1

M → T in AD3. Ref.49 Ref.66

VAR_006421

Natural variant

139

1

M → V in AD3. Ref.51 Ref.73

VAR_006422

Natural variant

143

1

I → F in AD3. Ref.67

VAR_006423

Natural variant

143

1

I → T in AD3. Ref.48

VAR_006424

Natural variant

146

1

M → I in AD3.

VAR_006425

Natural variant

146

1

M → L in AD3. Ref.1 Ref.66

VAR_006426

Natural variant

146

1

M → V in AD3. Ref.51

VAR_006427

Natural variant

147

1

T → I in AD3. Ref.66

VAR_010123

Natural variant

163

1

H → R in AD3. Ref.1 Ref.49 Ref.52 Ref.60 Ref.66

VAR_006428

Natural variant

163

1

H → Y in AD3. Ref.51

VAR_006429

Natural variant

165

1

W → C in AD3. Ref.66

VAR_010124

Natural variant

166

1

L → P in AD3; onset in adolescence. Ref.80

VAR_016216

Natural variant

169

1

S → L in AD3. Ref.64

VAR_006430

Natural variant

169

1

S → P in AD3. Ref.70

VAR_006431

Natural variant

171

1

L → P in AD3. Ref.56

VAR_006432

Natural variant

173

1

L → W in AD3. Ref.66

VAR_010125

Natural variant

174

1

L → M in AD3. Ref.81

VAR_016217

Natural variant

205

1

F → L.
Corresponds to variant rs1042864 [ dbSNP | Ensembl ].

VAR_011876

Natural variant

206

1

G → A in AD3. Ref.78

VAR_016218

Natural variant

209

1

G → R in AD3. Ref.68

VAR_009210

Natural variant

209

1

G → V in AD3. Ref.60

VAR_006433

Natural variant

213

1

I → T in AD3. Ref.52

VAR_006434

Natural variant

219

1

L → P in AD3. Ref.71

VAR_010126

Natural variant

231

1

A → T in AD3. Ref.49 Ref.66

VAR_006435

Natural variant

231

1

A → V in AD3. Ref.59

VAR_006436

Natural variant

233

1

M → L in AD3. Ref.69

VAR_009211

Natural variant

233

1

M → T in AD3. Ref.55 Ref.66

VAR_006437

Natural variant

235

1

L → P in A3D. Ref.66

VAR_006438

Natural variant

246

1

A → E in AD3. Ref.1

VAR_006439

Natural variant

250

1

L → S in AD3.

VAR_006440

Natural variant

260

1

A → V in AD3. Ref.50 Ref.60

VAR_006441

Natural variant

262

1

L → F in AD3.

VAR_006442

Natural variant

263

1

C → R in AD3.

VAR_006443

Natural variant

264

1

P → L in AD3. Ref.49 Ref.60 Ref.66

VAR_006444

Natural variant

266

1

G → S in AD3. Ref.79

VAR_016219

Natural variant

267

1

P → S in AD3.

VAR_006445

Natural variant

267

1

P → T in AD3. Ref.51

VAR_006446

Natural variant

269

1

R → G in AD3.

VAR_006447

Natural variant

269

1

R → H in AD3.

VAR_006448

Natural variant

271

1

L → V in AD3. Ref.82

VAR_016220

Natural variant

278

1

R → T in AD3. Ref.55

VAR_006449

Natural variant

280

1

E → A in AD3. Ref.51 Ref.54

VAR_006450

Natural variant

280

1

E → G in AD3. Ref.51

VAR_006451

Natural variant

282

1

L → R in AD3. Ref.69

VAR_009212

Natural variant

285

1

A → V in AD3. Ref.50

VAR_006452

Natural variant

286

1

L → V in AD3. Ref.1

VAR_006453

Natural variant

289

1

S → C in AD3.

VAR_010127

Natural variant

315

1

Y → C Found in a renal cell carcinoma sample; somatic mutation. Ref.85

VAR_064747

Natural variant

318

1

E → 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 variant

333

1

D → G in CMD1U. Ref.83

VAR_064902

Natural variant

378

1

G → E in AD3. Ref.61

VAR_006455

Natural variant

384

1

G → A in AD3. Ref.48

VAR_006456

Natural variant

390

1

S → I in AD3. Ref.66

VAR_010128

Natural variant

392

1

L → V in AD3. Ref.49 Ref.50 Ref.66

VAR_006457

Natural variant

405

1

N → S in AD3. Ref.74

VAR_010129

Natural variant

409

1

A → T in AD3. Ref.69

VAR_009213

Natural variant

410

1

C → Y in AD3. Ref.49 Ref.60 Ref.66
Corresponds to variant rs661 [ dbSNP | Ensembl ].

VAR_006458

Natural variant

426

1

A → P in AD3. Ref.60

VAR_006459

Natural variant

431

1

A → E in AD3. Ref.77

VAR_025605

Natural variant

436

1

P → Q in AD3. Ref.64
Corresponds to variant rs28930977 [ dbSNP | Ensembl ].

VAR_006460

Natural variant

436

1

P → S in AD3. Ref.67

VAR_008141

Experimental info

Mutagenesis

66 – 72

7

Missing: No effect on interaction with GFAP. Ref.29

Mutagenesis

76 – 77

2

KY → AA: No effect on interaction with GFAP.

Mutagenesis

82 – 83

2

VI → EE: Loss of interaction with GFAP. Ref.29

Mutagenesis

82

1

V → K or E: Loss of interaction with GFAP. Ref.29

Mutagenesis

84 – 85

2

ML → EE: Loss of interaction with GFAP.

Mutagenesis

256

1

Y → F: Alters gamma-secretase cleavage specificity. Increased production of amyloid beta(42). No effect on enzymatic activity. Ref.36

Mutagenesis

257

1

D → 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

Mutagenesis

257

1

D → 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

Mutagenesis

286

1

L → A, E, P, Q, R or W: Increases production of amyloid beta in APP processing. Ref.25

Mutagenesis

286

1

L → E or R: Reduces production of NICD in NOTCH1 processing. Ref.25

Mutagenesis

292

1

M → D: Loss of endoproteolytic cleavage. Ref.19

Mutagenesis

310

1

S → A: Abolishes PKA-mediated phosphorylation; no effect on caspase-mediated cleavage. Ref.34

Mutagenesis

345

1

D → N: Abolishes caspase cleavage. Ref.16

Mutagenesis

346

1

S → A: Abolishes PKC-mediated phosphorylation; no effect on PKA-mediated phosphorylation. Ref.34

Mutagenesis

346

1

S → E: Inhibits caspase-mediated cleavage. Modulates progression of apoptosis. Ref.34

Mutagenesis

373

1

D → N: No effect on caspase cleavage. Ref.16

Mutagenesis

385

1

D → 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

Mutagenesis

385

1

D → 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

Mutagenesis

385

1

D → N: No effect on caspase cleavage. Ref.16 Ref.23 Ref.24 Ref.30 Ref.36

Mutagenesis

389

1

Y → F: Alters gamma-secretase cleavage specificity. Increased production of amyloid beta(42). No effect on enzymatic activity. Ref.36

Mutagenesis

433

1

P → A: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Slightly increased Abeta42/Abeta40 ratio. Ref.39

Mutagenesis

433

1

P → D, F, L, N or V: No endoproteolytic cleavage; no APP nor NOTCH1 processing. No detectable Abetano detectable Abeta. Ref.39

Mutagenesis

433

1

P → G: Very little endoproteolysis. Little APP processing. No NOTCH1 processing. Very low levels Abeta40 and no detectable Abeta42. Ref.39

Mutagenesis

434

1

A → C: Some loss of endoproteolytic cleavage. Some loss of APP and NOTCH1 processing. Six-fold increase in Abeta42/Abeta40 ratio. Ref.39

Mutagenesis

434

1

A → D, I, L or V: No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable Abeta. Ref.39

Mutagenesis

434

1

A → G: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Reduced Abeta42/Abeta40 ratio. Ref.39

Mutagenesis

435

1

L → A: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Greatly reduced Abeta42/Abeta40 ratio. Ref.39

Mutagenesis

435

1

L → F: No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable Abeta. Ref.39

Mutagenesis

435

1

L → G: Greatly reduced endoproteolytic cleavage. Very little APP and NOTCH1 processing. Very low levels of Abeta40 and no detectable Abeta42. Ref.39

Mutagenesis

435

1

L → I: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Ref.39

Mutagenesis

435

1

L → V: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Some increase in Abeta42/Abeta40 ratio. Ref.39

Sequence conflict

128

1

R → G in AAL16811. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

467

Helix Strand Turn

Details...

Helix

293 – 299

7

Beta strand

341 – 345

5

Helix

356 – 368

13

Turn

383 – 385

3

Helix

386 – 399

14

Turn

403 – 406

4

Helix

407 – 428

22

Beta strand

433 – 437

5

Helix

442 – 449

8

Turn

450 – 453

4

Helix

456 – 458

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (I-467) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 5E0F451EF82BCF20	FASTA	467	52,668
	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
	Isoform 2 (I-463) [UniParc]. Checksum: 955325791A81470F	FASTA	463	52,197
	10 20 30 40 50 60 MTELPAPLSY FQNAQMSEDN HLSNTNDNRE RQEHNDRRSL GHPEPLSNGR PQGNSRQVVE 70 80 90 100 110 120 QDEEEDEELT LKYGAKHVIM LFVPVTLCMV VVVATIKSVS FYTRKDGQLI YTPFTEDTET 130 140 150 160 170 180 VGQRALHSIL NAAIMISVIV VMTILLVVLY KYRCYKVIHA WLIISSLLLL FFFSFIYLGE 190 200 210 220 230 240 VFKTYNVAVD YITVALLIWN FGVVGMISIH WKGPLRLQQA YLIMISALMA LVFIKYLPEW 250 260 270 280 290 300 TAWLILAVIS VYDLVAVLCP KGPLRMLVET AQERNETLFP ALIYSSTMVW LVNMAEGDPE 310 320 330 340 350 360 AQRRVSKNSK YNAESTERES QDTVAENDDG GFSEEWEAQR DSHLGPHRST PESRAAVQEL 370 380 390 400 410 420 SSSILAGEDP EERGVKLGLG DFIFYSVLVG KASATASGDW NTTIACFVAI LIGLCLTLLL 430 440 450 460 LAIFKKALPA LPISITFGLV FYFATDYLVQ PFMDQLAFHQ FYI
	Isoform 3 (I-374) [UniParc]. Checksum: 5172C076410745BF	FASTA	374	42,287
	10 20 30 40 50 60 MTELPAPLSY FQNAQMSEDN HLSNTNDNRE RQEHNDRRSL GHPEPLSNGR PQGNSRQVVE 70 80 90 100 110 120 QDEEEDEELT LKYGAKHVIM LFVPVTLCMV VVVATIKSVS FYTRKDGQLI YTPFTEDTET 130 140 150 160 170 180 VGQRALHSIL NAAIMISVIV VMTILLVVLY KYRCYKVIHA WLIISSLLLL FFFSFIYLGE 190 200 210 220 230 240 VFKTYNVAVD YITVALLIWN FGVVGMISIH WKGPLRLQQA YLIMISALMA LVFIKYLPEW 250 260 270 280 290 300 TAWLILAVIS VYDLVAVLCP KGPLRMLVET AQERNETLFP ALIYSSTMVW LVNMAEGDPE 310 320 330 340 350 360 AQRRVSKNSK YNAERACLPP AAINLLSIAP MAPRLFMPKG ACRPTAQKGS HKTLLQRMMM 370 AGSVRNGKPR GTVI
	Isoform 4 (Minilin) [UniParc]. Checksum: 95C68A7EA0020874	FASTA	184	21,073
	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 VSMRHRSLLS TLFFLWLGIL VTVT
	Isoform 5 [UniParc]. Checksum: A09D682EC6F568FD	FASTA	378	42,757
	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 KNSKYNAERA CLPPAAINLL SIAPMAPRLF MPKGACRPTA QKGSHKTLLQ 370 RMMMAGSVRN GKPRGTVI
	Isoform 6 [UniParc]. Checksum: 4855BDDCCD1D7D71	FASTA	409	46,328
	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 KNSKYNAERG VKLGLGDFIF YSVLVGKASA TASGDWNTTI ACFVAILIGL 370 380 390 400 CLTLLLLAIF KKALPALPIS ITFGLVFYFA TDYLVQPFMD QLAFHQFYI
	Isoform 7 [UniParc]. Checksum: C3930DB665C32929	FASTA	434	48,997
	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 AVISVYSTMV WLVNMAEGDP EAQRRVSKNS KYNAESTERE SQDTVAENDD 310 320 330 340 350 360 GGFSEEWEAQ RDSHLGPHRS TPESRAAVQE LSSSILAGED PEERGVKLGL GDFIFYSVLV 370 380 390 400 410 420 GKASATASGD WNTTIACFVA ILIGLCLTLL LLAIFKKALP ALPISITFGL VFYFATDYLV 430 QPFMDQLAFH QFYI

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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. , 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. , 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. , 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. , 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. , 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.
+	Additional computationally mapped references.

Web resources

Alzheimer Research Forum

Presenilins mutations

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L42110 mRNA. Translation: AAB46416.1.
L76517 mRNA. Translation: AAB46370.1.
L76528 , 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.

IPI

IPI00028077.
IPI00068752.
IPI00219934.
IPI00289615.
IPI00337671.
IPI00514137.
IPI01018728.

PIR

S58396.
S63683.
S63684.

RefSeq

NP_000012.1. NM_000021.3.
NP_015557.2. NM_007318.2.

UniGene

Hs.3260.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KR6	NMR	-	A	292-467	[»]

ProteinModelPortal

P49768.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1134N.

IntAct

P49768. 33 interactions.

MINT

MINT-88325.

STRING

9606.ENSP00000326366.

Protein family/group databases

MEROPS

A22.001.

TCDB

1.A.54.1.1. presenilin ER Ca2+ leak channel (Presenilin) family.

PTM databases

PhosphoSite

P49768.

Polymorphism databases

DMDM

1709856.

Proteomic databases

PaxDb

P49768.

PRIDE

P49768.

Protocols and materials databases

DNASU

5663.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261970; ENSP00000261970; ENSG00000080815.
ENST00000324501; ENSP00000326366; ENSG00000080815.
ENST00000344094; ENSP00000339523; ENSG00000080815.
ENST00000357710; ENSP00000350342; ENSG00000080815.
ENST00000394157; ENSP00000377712; ENSG00000080815.
ENST00000394164; ENSP00000377719; ENSG00000080815.
ENST00000553855; ENSP00000452242; ENSG00000080815.
ENST00000555386; ENSP00000450845; ENSG00000080815.
ENST00000557511; ENSP00000451429; ENSG00000080815.

GeneID

5663.

KEGG

hsa:5663.

UCSC

uc001xnq.4. human.
uc001xnr.3. human.
uc001xnv.3. human.

Organism-specific databases

CTD

5663.

GeneCards

GC14P073603.

HGNC

HGNC:9508. PSEN1.

HPA

CAB006844.
HPA030760.

MIM

104311. gene.
600274. phenotype.
607822. phenotype.
613694. phenotype.
613737. phenotype.

neXtProt

NX_P49768.

Orphanet

275864. Behavioural 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.

PharmGKB

PA33855.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG237920.

HOVERGEN

HBG011375.

InParanoid

P49768.

KO

K04505.

OMA

AQRKVSK.

OrthoDB

EOG4TF0KN.

PhylomeDB

P49768.

Enzyme and pathway databases

Pathway_Interaction_DB

p75ntrpathway. p75(NTR)-mediated signaling.
ps1pathway. Presenilin action in Notch and Wnt signaling.
syndecan_3_pathway. Syndecan-3-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.
REACT_691. A third proteolytic cleavage releases NICD.

Gene expression databases

ArrayExpress

P49768.

Bgee

P49768.

CleanEx

HS_PSEN1.

Genevestigator

P49768.

GermOnline

ENSG00000080815. Homo sapiens.

Family and domain databases

InterPro

IPR002031. Pept_A22A_PS1.
IPR006639. Peptidase_A22.
IPR001108. Peptidase_A22A.
[Graphical view]

PANTHER

PTHR10202. PTHR10202. 1 hit.
PTHR10202:SF7. PTHR10202:SF7. 1 hit.

Pfam

PF01080. Presenilin. 1 hit.
[Graphical view]

PRINTS

PR01072. PRESENILIN.
PR01073. PRESENILIN1.

SMART

SM00730. PSN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P49768.

ChEMBL

CHEMBL2473.

ChiTaRS

PSEN1. human.

EvolutionaryTrace

P49768.

GenomeRNAi

5663.

NextBio

22006.

PMAP-CutDB

P49768.

SOURCE

Search...

Entry information

Entry name

PSN1_HUMAN

Accession

Primary (citable) accession number: P49768
Secondary accession number(s): B2R6D3 , O95465, Q14762, Q15719, Q15720, Q96P33, Q9UIF0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 161 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.