Aliases for PSEN2 Gene
External Ids for PSEN2 Gene
Previous HGNC Symbols for PSEN2 Gene
Previous GeneCards Identifiers for PSEN2 Gene
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor such that, they either directly regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified. [provided by RefSeq, Jul 2008]
GeneCards Summary for PSEN2 Gene
PSEN2 (Presenilin 2) is a Protein Coding gene. Diseases associated with PSEN2 include cardiomyopathy, dilated, 1v and alzheimer disease-4. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include endopeptidase activity and aspartic-type endopeptidase activity. An important paralog of this gene is PSEN1.
UniProtKB/Swiss-Prot for PSEN2 Gene
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.
Secretases are a group of enzymes involved in the proteolytic cleavage of amyloid precursor protein (APP). There are three types of secretases, alpha-secretase, beta-secretase and gamma-secretase. gamma-Secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is itself an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. Presenilin is an aspartic protease and the catalytic subunit of the complex. There are two important substrates of gamma-secretase; amyloid precursor protein (APP) and Notch. gamma-secretase can cleave several sites within APP, and the most common products are Abeta40 and Abeta42. Abeta42 is fibrillogenic and associated with disease states, notably Alzheimer's disease. gamma-Secretase catalyzes the second step in Notch protein cleavage. gamma-Secretase cleaves within the transmembrane domain of Notch, releasing the intracellular domain (Nbeta) into the cytoplasm. Nbeta moves to the nucleus where it can regulate gene expression by activating the transcription factor CSL. This gamma-secretase-Notch signaling pathway has a role in promoting angiogenesis in the embryo and wound healing in the adult.