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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) . Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes. 7 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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| Protein type: Cell surface; EC 3.4.23.-; Membrane protein, integral; Membrane protein, multi-pass; Mitochondrial; Protease |
| Chromosomal Location of human Ortholog: 14q24.2 |
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Cellular Component:
aggresome; apical plasma membrane; azurophil granule membrane; cell cortex; cell junction; cell surface; centrosome; ciliary rootlet; dendritic shaft; early endosome membrane; endoplasmic reticulum; endoplasmic reticulum membrane; gamma-secretase complex; glutamatergic synapse; Golgi apparatus; Golgi membrane; growth cone; kinetochore; lysosomal membrane; membrane; membrane raft; mitochondrial inner membrane; mitochondrion; neuromuscular junction; neuron projection; neuronal cell body; nuclear membrane; nuclear outer membrane; nucleoplasm; nucleus; perinuclear region of cytoplasm; plasma membrane; postsynapse; presynaptic membrane; protein-containing complex; rough endoplasmic reticulum; sarcolemma; smooth endoplasmic reticulum; synaptic vesicle; Z disc
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Molecular Function:
aspartic endopeptidase activity, intramembrane cleaving; aspartic-type endopeptidase activity; ATPase binding; beta-catenin binding; cadherin binding; calcium channel activity; endopeptidase activity; growth factor receptor binding; PDZ domain binding; protein binding
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Biological Process:
amyloid precursor protein catabolic process; amyloid precursor protein metabolic process; amyloid-beta formation; amyloid-beta metabolic process; apoptotic signaling pathway; astrocyte activation; astrocyte activation involved in immune response; autophagosome assembly; blood vessel development; brain morphogenesis; Cajal-Retzius cell differentiation; calcium ion transmembrane transport; calcium ion transport; cell fate specification; cell-cell adhesion; cellular response to amyloid-beta; cerebellum development; cerebral cortex cell migration; choline transport; DNA damage response; dorsal/ventral neural tube patterning; embryonic limb morphogenesis; endoplasmic reticulum calcium ion homeostasis; epithelial cell proliferation; heart looping; hematopoietic progenitor cell differentiation; intracellular signal transduction; L-glutamate import across plasma membrane; learning or memory; locomotion; membrane protein ectodomain proteolysis; memory; mitochondrial transport; myeloid dendritic cell 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 low-density lipoprotein receptor activity; negative regulation of neuron apoptotic process; negative regulation of transcription by RNA polymerase II; negative regulation of ubiquitin-dependent protein catabolic process; negative regulation of ubiquitin-protein transferase activity; neural retina development; neuron apoptotic process; neuron cellular homeostasis; neuron development; 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 DNA-templated transcription; positive regulation of gene expression; positive regulation of glycolytic process; 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 receptor recycling; positive regulation of tumor necrosis factor production; post-embryonic development; protein catabolic process at postsynapse; protein glycosylation; protein processing; protein transport; regulation of canonical Wnt signaling pathway; regulation of gene expression; regulation of neuron projection development; regulation of phosphorylation; regulation of postsynapse organization; regulation of resting membrane potential; regulation of synaptic plasticity; regulation of synaptic transmission, glutamatergic; regulation of synaptic vesicle cycle; response to oxidative stress; sequestering of calcium ion; 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
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Disease: Acne Inversa, Familial, 3; Alzheimer Disease 3; Cardiomyopathy, Dilated, 1u; Frontotemporal Dementia; Pick Disease Of Brain
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Reference #:
P49768
(UniProtKB)
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Alt. Names/Synonyms: ACNINV3; AD3; FAD; 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
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Gene Symbols: PSEN1
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Molecular weight:
52,668 Da
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Basal Isoelectric point:
5.18
Predict pI for various phosphorylation states
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CST Pathways:
Alzheimer's Disease
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ErbB/HER Signaling
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ESC Pluripotency and Differentiation
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Notch Signaling
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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