PSEN1 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 (amyloid-beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin). Under conditions of apoptosis or calcium influx, cleaves CDH1. This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling. Required for normal embryonic brain and skeleton development, and for normal angiogenesis. Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis. Involved in the regulation of neurite outgrowth. Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression. Belongs to the peptidase A22A family. Detected in azurophile granules in neutrophils and in platelet cytoplasmic granules (at protein level) (PubMed:11987239). Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes (PubMed:7596406, PubMed:8641442, PubMed:8574969). 7 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Cell surface; EC 3.4.23.-; Membrane protein, integral; Membrane protein, multi-pass; Mitochondrial; Protease
Chromosomal Location of Human Ortholog: 12 D1|12 38.84 cM
Cellular Component:  aggresome; axon; cell cortex; cell junction; cell projection; cell surface; centrosome; ciliary rootlet; cytoplasm; cytoplasmic vesicle; dendrite; dendritic shaft; early endosome; endoplasmic reticulum; endosome; gamma-secretase complex; Golgi apparatus; growth cone; integral component of membrane; integral component of plasma membrane; integral component of presynaptic membrane; kinetochore; lysosomal membrane; membrane; membrane raft; membrane-bounded organelle; mitochondrial inner membrane; mitochondrion; neuromuscular junction; neuron projection; neuronal cell body; nuclear membrane; nuclear outer membrane; nucleus; plasma membrane; protein-containing complex; rough endoplasmic reticulum; sarcolemma; smooth endoplasmic reticulum; synapse; synaptic membrane; synaptic vesicle
Molecular Function:  aspartic endopeptidase activity, intramembrane cleaving; aspartic-type endopeptidase activity; beta-catenin binding; cadherin binding; calcium channel activity; endopeptidase activity; hydrolase activity; PDZ domain binding; peptidase activity; protein binding
Biological Process:  activation of MAPKK activity; amyloid precursor protein catabolic process; amyloid precursor protein metabolic process; amyloid-beta formation; amyloid-beta metabolic process; apoptotic process; astrocyte activation; astrocyte activation involved in immune response; autophagosome assembly; autophagy; blood vessel development; brain development; brain morphogenesis; Cajal-Retzius cell differentiation; cell adhesion; cell fate specification; cell-cell adhesion; cellular calcium ion homeostasis; cellular protein metabolic process; cellular response to amyloid-beta; cellular response to DNA damage stimulus; cerebral cortex cell migration; cerebral cortex development; choline transport; dorsal/ventral neural tube patterning; embryonic limb morphogenesis; endoplasmic reticulum calcium ion homeostasis; epithelial cell proliferation; forebrain development; heart development; heart looping; hematopoietic progenitor cell differentiation; intracellular signal transduction; learning or memory; locomotion; long-term synaptic potentiation; membrane protein ectodomain proteolysis; memory; mitochondrial transport; modulation of age-related behavioral decline; myeloid dendritic cell differentiation; myeloid leukocyte differentiation; negative regulation of apoptotic process; negative regulation of apoptotic signaling pathway; negative regulation of axonogenesis; negative regulation of core promoter binding; negative regulation of epidermal growth factor-activated receptor activity; negative regulation of gene expression; negative regulation of neuron apoptotic process; negative regulation of protein kinase activity; negative regulation of protein phosphorylation; negative regulation of transcription by RNA polymerase II; negative regulation of ubiquitin-dependent protein catabolic process; negative regulation of ubiquitin-protein transferase activity; neurogenesis; neuron apoptotic process; neuron development; neuron differentiation; neuron migration; neuron projection maintenance; Notch receptor processing; Notch signaling pathway; positive regulation of amyloid fibril formation; positive regulation of apoptotic process; positive regulation of catalytic activity; positive regulation of coagulation; positive regulation of dendritic spine development; positive regulation of gene expression; positive regulation of L-glutamate import across plasma membrane; positive regulation of MAP kinase activity; positive regulation of phosphorylation; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein binding; positive regulation of protein import into nucleus; positive regulation of protein kinase activity; positive regulation of protein phosphorylation; positive regulation of receptor recycling; positive regulation of transcription, DNA-templated; post-embryonic development; protein glycosylation; protein maturation; protein processing; protein transport; proteolysis; regulation of canonical Wnt signaling pathway; regulation of epidermal growth factor-activated receptor activity; regulation of neuron projection development; regulation of phosphorylation; regulation of protein binding; regulation of resting membrane potential; regulation of synaptic plasticity; regulation of synaptic transmission, glutamatergic; response to oxidative stress; segmentation; skeletal system morphogenesis; skin morphogenesis; smooth endoplasmic reticulum calcium ion homeostasis; somitogenesis; synapse organization; synaptic vesicle targeting; T cell activation involved in immune response; T cell receptor signaling pathway; thymus development
Reference #:  P49769 (UniProtKB)
Alt. Names/Synonyms: Ad3h; presenilin 1; Presenilin-1; Presenilin-1 CTF subunit; Presenilin-1 CTF12; Presenilin-1 NTF subunit; Protein S182; PS-1; PS1; PS1-CTF12; Psen1; PSN1; Psnl1; S182
Gene Symbols: Psen1
Molecular weight: 52,640 Da
Basal Isoelectric point: 5.23  Predict pI for various phosphorylation states
CST Pathways:  Alzheimer's Disease  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  Notch Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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PSEN1

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene