FUNCTION: SwissProt: P49810 # 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. May function in the cytoplasmic partitioning of proteins.SIZE: 448 amino acids; 50140 Da SUBUNIT: Interacts with DOCK3 (By similarity). 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, although other components may exist. Interacts with HERPUD1, FLNA, FLNB and PARL.SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein.TISSUE SPECIFICITY: Isoform 1 is seen in the placenta, skeletal muscle and heart while isoform 2 is seen in the heart, brain, placenta, liver, skeletal muscle and kidney.DOMAIN: SwissProt: P49810 The PAL motif is required for normal active site conformation (By similarity).PTM: Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments. & Phosphorylated on serine residues.DISEASE: SwissProt: P49810 # Defects in PSEN2 are the cause of Alzheimer disease type 4 (AD4) [MIM:606889, 104300]. AD is an autosomal dominant neurodegenerative disorder characterized by progressive dementia, parkinsonism, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. Early onset AD is the most severe form of the disease, with complete penetrance and an onset occurring as early as 30 years of age. The second form is late- onset AD (LOAD), with mean age of onset greater than 58 years. & Three causative genes have been identified that when mutated lead to presenile Alzheimer DISEASE: APP (amyloid precursor protein gene), PSEN1 and PSEN2. These three genes account for half of the families with autosomal dominant presenile AD, which represent approximately 10% of the whole AD population. In addition, apolipoprotein E has been identified as a risk- modifying locus.SIMILARITY: Belongs to the peptidase A22A family.，官网链接：https://www.sigmaaldrich.cn/product/mm/ag216 默克 科研、开发、生产。 作为生命科学行业的全球领先供应商，我们致力于为科研、生物技术开发和生产，以及制药药物疗法开发和生产提供各类解决方案和服务。

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