Aliases for PSENEN Gene
External Ids for PSENEN Gene
Previous GeneCards Identifiers for PSENEN Gene
Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase. Mutations resulting in haploinsufficiency for this gene cause familial acne inversa-2 (ACNINV2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
GeneCards Summary for PSENEN Gene
PSENEN (Presenilin Enhancer Gamma Secretase Subunit) is a Protein Coding gene. Diseases associated with PSENEN include acne inversa, familial, 2 and hidradenitis. Among its related pathways are PI-3K cascade and Signaling by FGFR. An important paralog of this gene is ENSG00000188223.
UniProtKB/Swiss-Prot for PSENEN Gene
Essential 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). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.
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.