PSN1_HUMAN
Source:
PM23856902
PM22954596
Marked as 'Integral membrane protein'
Confidence:
medium (present in either hRBCD or BSc_CH or PM22954596)
Search PubMed for
(RBC AND this entry)
Gene names:
PSEN1
, AD3, PS1, PSNL1
Protein names and data:
PSN1_HUMAN
, Presenilin-1; PS-1; 3.4.23.-
, Protein S182; Presenilin-1 NTF subunit; Presenilin-1 CTF subunit; Presenilin-1 CTF12; PS1-CTF12
Lenght: 467 a.a.
Mass: 52668 Da
fasta formatted sequence
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.
Disease:
( OMIM:
104311
600274
607822
613694
613737
)
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. 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. 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.
Cellular 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.
Tissue specificity:
Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes.
Genetic variants
79 - 79
A -> V (in AD3; no effect on interaction with GFAP). VAR_006413
82 - 82
V -> L (in AD3; no effect on interaction with GFAP). VAR_006414
92 - 92
C -> S (in AD3). VAR_016214
96 - 96
V -> F (in AD3). VAR_006415
105 - 105
F -> L (in AD3). VAR_009208
113 - 113
L -> P (in frontotemporal dementia). VAR_016215
115 - 115
Y -> C (in AD3). VAR_006416
115 - 115
Y -> H (in AD3). VAR_006417
116 - 116
T -> N (in AD3). VAR_010120
117 - 117
P -> L (in AD3). VAR_009209
120 - 120
E -> D (in AD3). VAR_006418
120 - 120
E -> K (in AD3). VAR_006419
134 - 134
L -> R (in AD3; uncertain pathological significance). VAR_070023
135 - 135
N -> D (in AD3). VAR_010121
139 - 139
M -> I (in AD3). VAR_006420
139 - 139
M -> K (in AD3). VAR_010122
139 - 139
M -> T (in AD3). VAR_006421
139 - 139
M -> V (in AD3). VAR_006422
143 - 143
I -> F (in AD3). VAR_006423
143 - 143
I -> T (in AD3). VAR_006424
146 - 146
M -> I (in AD3). VAR_006425
146 - 146
M -> L (in AD3). VAR_006426
146 - 146
M -> V (in AD3). VAR_006427
147 - 147
T -> I (in AD3). VAR_010123
163 - 163
H -> R (in AD3). VAR_006428
163 - 163
H -> Y (in AD3). VAR_006429
165 - 165
W -> C (in AD3). VAR_010124
166 - 166
L -> P (in AD3; onset in adolescence). VAR_016216
169 - 169
S -> L (in AD3). VAR_006430
169 - 169
S -> P (in AD3). VAR_006431
171 - 171
L -> P (in AD3). VAR_006432
173 - 173
L -> W (in AD3). VAR_010125
174 - 174
L -> M (in AD3). VAR_016217
205 - 205
F -> L (in dbSNP:rs1042864). VAR_011876
1042864
206 - 206
G -> A (in AD3). VAR_016218
209 - 209
G -> R (in AD3). VAR_009210
209 - 209
G -> V (in AD3). VAR_006433
213 - 213
I -> T (in AD3). VAR_006434
214 - 214
H -> Y (probable disease-associated mutation found in a patient with dementia). VAR_070024
219 - 219
L -> P (in AD3). VAR_010126
231 - 231
A -> T (in AD3). VAR_006435
231 - 231
A -> V (in AD3). VAR_006436
233 - 233
M -> L (in AD3). VAR_009211
233 - 233
M -> T (in AD3). VAR_006437
235 - 235
L -> P (in A3D). VAR_006438
246 - 246
A -> E (in AD3). VAR_006439
250 - 250
L -> S (in AD3). VAR_006440
260 - 260
A -> V (in AD3). VAR_006441
262 - 262
L -> F (in AD3). VAR_006442
262 - 262
L -> V (in AD3). VAR_070025
263 - 263
C -> R (in AD3). VAR_006443
264 - 264
P -> L (in AD3). VAR_006444
266 - 266
G -> S (in AD3). VAR_016219
267 - 267
P -> S (in AD3). VAR_006445
267 - 267
P -> T (in AD3). VAR_006446
269 - 269
R -> G (in AD3). VAR_006447
269 - 269
R -> H (in AD3). VAR_006448
271 - 271
L -> V (in AD3). VAR_016220
278 - 278
R -> T (in AD3). VAR_006449
280 - 280
E -> A (in AD3). VAR_006450
280 - 280
E -> G (in AD3). VAR_006451
282 - 282
L -> R (in AD3). VAR_009212
285 - 285
A -> V (in AD3). VAR_006452
286 - 286
L -> V (in AD3). VAR_006453
289 - 289
S -> C (in AD3). VAR_010127
315 - 315
Y -> C (found in a renal cell carcinoma sample; somatic mutation). VAR_064747
318 - 318
E -> G (in dbSNP:rs17125721). VAR_006454
17125721
333 - 333
D -> G (in CMD1U). VAR_064902
378 - 378
G -> E (in AD3). VAR_006455
384 - 384
G -> A (in AD3). VAR_006456
390 - 390
S -> I (in AD3). VAR_010128
392 - 392
L -> V (in AD3). VAR_006457
396 - 396
A -> T (in AD3; uncertain pathological significance). VAR_070026
405 - 405
N -> S (in AD3). VAR_010129
409 - 409
A -> T (in AD3). VAR_009213
410 - 410
C -> Y (in AD3; dbSNP:rs661). VAR_006458
661
426 - 426
A -> P (in AD3). VAR_006459
431 - 431
A -> E (in AD3). VAR_025605
436 - 436
P -> Q (in AD3; dbSNP:rs28930977). VAR_006460
28930977
436 - 436
P -> S (in AD3). VAR_008141
Database cross-references
UniProt:
P49768
Ensembl:
ENST00000261970
Ensembl:
ENST00000324501
Ensembl:
ENST00000344094
Ensembl:
ENST00000357710
Ensembl:
ENST00000394157
Ensembl:
ENST00000394164
Ensembl:
ENST00000553855
Ensembl:
ENST00000555386
Ensembl:
ENST00000557511
MIM:
104311
MIM:
600274
MIM:
607822
MIM:
613694
MIM:
613737
neXtProt:
NX_P49768
Antibodypedia:
P49768
(may not find the protein thus also not any antibody)
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