功能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.
组织特异性Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes.
疾病相关Defects in PSEN1 are a cause of Alzheimer disease type 3 (AD3) [MIM:607822]. AD3 is 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. Defects in PSEN1 are a cause of frontotemporal dementia [MIM:600274]. Defects in PSEN1 are the cause of cardiomyopathy dilated type 1U (CMD1U) [MIM:613694]. It is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Defects in PSEN1 are the cause of acne inversa familial type 3 (ACNIF3) [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.
序列相似性Belongs to the peptidase A22A family.
结构域The PAL motif is required for normal active site conformation.
翻译后修饰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. After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis.
细胞定位Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell surface. 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.
ICC/IF image of ab71181 stained HeLa cells. The cells were 4% PFA fixed (10 min) and then incubated in 1%BSA / 10% normal goat serum / 0.3M glycine in 0.1% PBS-Tween for 1h to permeabilise the cells and block non-specific protein-protein interactions. The cells were then incubated with the antibody (ab71181, 5µg/ml) overnight at +4°C. The secondary antibody (green) was Alexa Fluor® 488 goat anti-rabbit IgG (H+L) used at a 1/1000 dilution for 1h. Alexa Fluor® 594 WGA was used to label plasma membranes (red) at a 1/200 dilution for 1h. DAPI was used to stain the cell nuclei (blue) at a concentration of 1.43µM. This antibody also gave a positive result in 4% PFA fixed (10 min) MCF7 cells at 5µg/ml, and in 100% methanol fixed (5 min) MCF7 cells at 5µg/ml.
Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Presenilin 1 antibody (ab71181)This image is a courtesy of Abreview submitted by Antibody Solutions Ltd
ab71181 staining Presenilin 1 mouse kidney tissue section by Immunohistochemistry (Formalin/ PFA fixed paraffin-embedded tissue sections). Tissue underwent fixation in formaldehyde, heat mediated antigen retrieval and blocking (5 minutes/peroxidase block and 10 minutes/protein block) for 15 minutes at 200C. The primary antibody was diluted 1/2000 and incubated with the sample for 45 minutes at 200C. A HRP conjugated goat polyclonal to rabbit IgG was used undiluted as secondary antibody.
IHC image of Presenilin 1 staining in human kidney formalin fixed paraffin embedded tissue section, performed on a Leica BondTM system using the standard protocol F. The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH6, epitope retrieval solution 1) for 20 mins. The section was then incubated with ab71181, 1µg/ml, for 15 mins at room temperature and detected using an HRP conjugated compact polymer system. DAB was used as the chromogen. The section was then counterstained with haematoxylin and mounted with DPX.
For other IHC staining systems (automated and non-automated) customers should optimize variable parameters such as antigen retrieval conditions, primary antibody concentration and antibody incubation times.
Western blot - Anti-Presenilin 1 antibody (ab71181)
All lanes : Anti-Presenilin 1 antibody (ab71181)
Lane 1 : Liver (Mouse) Tissue Lysate Lane 2 : Kidney (Mouse) Tissue Lysate Lane 3 : Kidney (Rat) Tissue Lysate
Lysates/proteins at 10 µg per lane.
Secondary Goat Anti-Rabbit IgG H&L (HRP) preadsorbed (ab97080) at 1/5000 dilution developed using the ECL technique
Schiffmacher AT et al. Cadherin-6B is proteolytically processed during epithelial-to-mesenchymal transitions of the cranial neural crest. Mol Biol Cell25:41-54 (2014).
Read more (PubMed: 24196837) »
Bhatnagar S et al. Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma. Front Mol Neurosci7:2 (2014).
Read more (PubMed: 24550773) »