======= PSEN1 ======= == Gene Information == * **Official Symbol**: PSEN1 * **Official Name**: presenilin 1 * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5663|5663]] * **UniProt**: [[https://www.uniprot.org/uniprot/P49768|P49768]] * **Interactions**: [[https://thebiogrid.org/search.php?search=PSEN1&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PSEN1|Open PubMed]] * **OMIM**: [[https://omim.org/entry/104311|Open OMIM]] == Function Summary == * **Entrez Summary**: Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in 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 are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]. * **UniProt Summary**: 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) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335). 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 (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). 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) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). 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 (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:9738936}. |Presenilin| |Cajal-Retzius cell differentiation| |negative regulation of core promoter binding| |smooth endoplasmic reticulum calcium ion homeostasis| |positive regulation of L-glutamate import across plasma membrane| |negative regulation of low-density lipoprotein receptor activity| |astrocyte activation involved in immune response| |positive regulation of amyloid fibril formation| |synaptic vesicle targeting| |regulation of L-glutamate import across plasma membrane| |positive regulation of neurotransmitter uptake| |Notch receptor processing, ligand-dependent| |gamma-secretase complex| |amyloid-beta formation| |aspartic endopeptidase activity, intramembrane cleaving| |choline transport| |regulation of resting membrane potential| |regulation of amyloid fibril formation| |regulation of amino acid transmembrane transport| |positive regulation of anion transmembrane transport| |regulation of core promoter binding| |regulation of amino acid import across plasma membrane| |modulation of age-related behavioral decline| |skin morphogenesis| |ciliary rootlet| |neuron projection maintenance| |Notch receptor processing| |amyloid precursor protein catabolic process| |negative regulation of epidermal growth factor-activated receptor activity| |positive regulation of receptor recycling| |negative regulation of ubiquitin-protein transferase activity| |dorsal/ventral neural tube patterning| |amyloid precursor protein metabolic process| |myeloid dendritic cell differentiation| |positive regulation of amino acid transport| |astrocyte activation| |membrane protein intracellular domain proteolysis| |regulation of neurotransmitter uptake| |amyloid-beta metabolic process| |positive regulation of tumor necrosis factor biosynthetic process| |negative regulation of transcription regulatory region DNA binding| |aspartic-type endopeptidase activity| |myeloid dendritic cell activation| |endoplasmic reticulum calcium ion homeostasis| |positive regulation of glycolytic process| |membrane protein ectodomain proteolysis| |regulation of receptor recycling| |cerebral cortex neuron differentiation| |nuclear outer membrane| |positive regulation of coagulation| |smooth endoplasmic reticulum| |regulation of anion transmembrane transport| |regulation of epidermal growth factor-activated receptor activity| |negative regulation of protein tyrosine kinase activity| |regulation of tumor necrosis factor biosynthetic process| |positive regulation of response to drug| |regulation of amino acid transport| |organic cation transport| |dendritic cell differentiation| |brain morphogenesis| |neural tube patterning| |positive regulation of organic acid transport| |positive regulation of amine transport| |astrocyte development| |dendritic shaft| |membrane protein proteolysis| |positive regulation of protein import into nucleus| |glial cell activation| |positive regulation of neurotransmitter transport| |positive regulation of protein import| |cellular response to amyloid-beta| |neuron projection organization| |neuroinflammatory response| |aggresome| |positive regulation of dendritic spine development| |cerebral cortex cell migration| |neuron apoptotic process| |negative regulation of endocytosis| |thymus development| |positive regulation of nucleotide metabolic process| |positive regulation of purine nucleotide metabolic process| |positive regulation of ATP metabolic process| |negative regulation of epidermal growth factor receptor signaling pathway| |negative regulation of ubiquitin-dependent protein catabolic process| |response to amyloid-beta| |positive regulation of anion transport| |negative regulation of peptidyl-tyrosine phosphorylation| |negative regulation of ERBB signaling pathway| |regulation of ubiquitin-protein transferase activity| |neuron death| |regulation of transcription regulatory region DNA binding| |ammonium transport| |calcium channel activity| |activation of MAPKK activity| |astrocyte differentiation| |negative regulation of DNA binding| |regulation of protein import into nucleus| |neural retina development| |integral component of presynaptic membrane| |negative regulation of signaling receptor activity| |regulation of protein import| |regulation of organic acid transport| |telencephalon cell migration| |azurophil granule membrane| |heart looping| |rough endoplasmic reticulum| |forebrain cell migration| |autophagosome assembly| |positive regulation of nucleocytoplasmic transport| |synaptic vesicle exocytosis| |T cell activation involved in immune response| |autophagosome organization| |somitogenesis| |determination of heart left/right asymmetry| |embryonic heart tube morphogenesis| |positive regulation of cytokine biosynthetic process| |exocytic process| |negative regulation of axonogenesis| |regulation of synaptic transmission, glutamatergic| |negative regulation of proteolysis involved in cellular protein catabolic process| |regulation of dendritic spine development| |positive regulation of dendrite development| |negative regulation of protein ubiquitination| |positive regulation of protein localization to nucleus| |embryonic heart tube development| |endopeptidase activity| |neuromuscular junction| |regulation of glycolytic process| |positive regulation of carbohydrate metabolic process| |dorsal/ventral pattern formation| |regulation of coagulation| |positive regulation of proteasomal ubiquitin-dependent protein catabolic process| |somite development| |negative regulation of protein modification by small protein conjugation or removal| |regulation of epidermal growth factor receptor signaling pathway| |beta-catenin binding| |kinetochore| |positive regulation of tumor necrosis factor production| |ephrin receptor signaling pathway| |hematopoietic progenitor cell differentiation| |epithelial cell proliferation| |negative regulation of cellular protein catabolic process| |positive regulation of tumor necrosis factor superfamily cytokine production| |cell fate specification| |PDZ domain binding| |regulation of carbohydrate catabolic process| |regulation of protein tyrosine kinase activity| |post-embryonic development| |vesicle targeting| |regulation of ERBB signaling pathway| |regulation of amine transport| |positive regulation of protein binding| |regulation of anion transport| |segmentation| |positive regulation of ubiquitin-dependent protein catabolic process| |negative regulation of cell morphogenesis involved in differentiation| |regulation of response to drug| |sarcolemma| |signal release from synapse| |neurotransmitter secretion| |cerebellum development| |positive regulation of proteasomal protein catabolic process| |regulation of cytokine biosynthetic process| |regulation of nucleocytoplasmic transport| |glial cell development| |lymphocyte activation involved in immune response| |metencephalon development| |myeloid leukocyte differentiation| |regulation of protein localization to nucleus| |regulation of purine nucleotide metabolic process| |cerebral cortex development| |memory| |determination of left/right symmetry| |synaptic vesicle cycle| |regulation of nucleotide metabolic process| |neuron migration| |synaptic vesicle| |positive regulation of proteolysis involved in cellular protein catabolic process| |regulation of ATP metabolic process| |regulation of proteasomal ubiquitin-dependent protein catabolic process| |determination of bilateral symmetry| |specification of symmetry| |embryonic limb morphogenesis| |regulation of DNA binding| |embryonic appendage morphogenesis| |Notch signaling pathway| |growth cone| |vesicle-mediated transport in synapse| |vacuole organization| |negative regulation of protein catabolic process| |cell cortex| |positive regulation of small molecule metabolic process| |retina development in camera-type eye| |positive regulation of cellular protein catabolic process| |regulation of neurotransmitter transport| |negative regulation of neuron apoptotic process| |regulation of tumor necrosis factor production| |regulation of dendrite development| |limb morphogenesis| |appendage morphogenesis| |hindbrain development| |early endosome membrane| |regulation of tumor necrosis factor superfamily cytokine production| |regulation of ubiquitin-dependent protein catabolic process| |positive regulation of intracellular protein transport| |negative regulation of neuron projection development| |positive regulation of ion transmembrane transport| |protein processing| |regulation of generation of precursor metabolites and energy| |neural tube development| |macroautophagy| |signal release| |glial cell differentiation| |negative regulation of binding| |regulation of signaling receptor activity| |pallium development| |establishment of vesicle localization| |T cell receptor signaling pathway| |positive regulation of binding| |central nervous system neuron differentiation| |neurotransmitter transport| |limb development| |appendage development| |negative regulation of cell projection organization| |regulation of proteasomal protein catabolic process| |vesicle localization| |regulation of axonogenesis| |regulation of synaptic plasticity| |positive regulation of supramolecular fiber organization| |calcium ion transmembrane transport| |regulation of protein ubiquitination| |positive regulation of transmembrane transport| |regulation of carbohydrate metabolic process| |regulation of endocytosis| |regulation of neuron apoptotic process| |negative regulation of neuron death| |positive regulation of intracellular transport| |gliogenesis| |mitochondrial transport| |positive regulation of protein catabolic process| |regulation of proteolysis involved in cellular protein catabolic process| |anterior/posterior pattern specification| |regulation of protein binding| |myeloid cell differentiation| |protein maturation| |negative regulation of apoptotic signaling pathway| |negative regulation of protein kinase activity| |membrane raft| |negative regulation of neuron differentiation| |regulation of protein modification by small protein conjugation or removal| |regulation of intracellular protein transport| |T cell activation| |skeletal system morphogenesis| |nuclear membrane| |negative regulation of kinase activity| |cell fate commitment| |regulation of cellular protein catabolic process| |calcium ion transport| |heart morphogenesis| |regulation of peptidyl-tyrosine phosphorylation| |negative regulation of cellular catabolic process| |macromolecule glycosylation| |telencephalon development| |protein glycosylation| |learning or memory| |process utilizing autophagic mechanism| |autophagy| |positive regulation of MAP kinase activity| |glycosylation| |synapse organization| |positive regulation of ion transport| |negative regulation of transferase activity| |aging| |positive regulation of neuron projection development| |regulation of canonical Wnt signaling pathway| |embryonic organ morphogenesis| |negative regulation of neurogenesis| |antigen receptor-mediated signaling pathway| |divalent metal ion transport| |cognition| |divalent inorganic cation transport| |regulation of cell morphogenesis involved in differentiation| |epithelial tube morphogenesis| |negative regulation of catabolic process| |cadherin binding| |regulation of neuron death| |negative regulation of nervous system development| |camera-type eye development| |neuron projection| |glycoprotein biosynthetic process| |positive regulation of cellular protein localization| |cellular response to peptide| |activation of protein kinase activity| |leukocyte differentiation| |regionalization| |negative regulation of cell development| |positive regulation of protein serine/threonine kinase activity| |regulation of MAP kinase activity| |regulation of supramolecular fiber organization| |regulation of intracellular transport| |regulation of neurotransmitter levels| |negative regulation of proteolysis| |positive regulation of proteolysis| |eye development| |regulation of Wnt signaling pathway| |visual system development| |establishment of organelle localization| |positive regulation of cellular catabolic process| |sensory system development| |positive regulation of neuron differentiation| |neuronal cell body| |regulation of binding| |positive regulation of cell projection organization| |skin development| |lymphocyte activation| |regulation of protein catabolic process| |glycoprotein metabolic process| |forebrain development| |response to oxidative stress| |mitochondrial inner membrane| |regulation of apoptotic signaling pathway| |negative regulation of protein phosphorylation| |gland development| |anterograde trans-synaptic signaling| |chemical synaptic transmission| |positive regulation of protein transport| |regulation of small molecule metabolic process| |regulation of membrane potential| |positive regulation of catabolic process| |morphogenesis of an epithelium| |embryonic organ development| |pattern specification process| |cellular calcium ion homeostasis| |trans-synaptic signaling| |modulation of chemical synaptic transmission| |regulation of trans-synaptic signaling| |negative regulation of phosphorylation| |positive regulation of cytokine production| |calcium ion homeostasis| |immune response-activating cell surface receptor signaling pathway| |positive regulation of establishment of protein localization| |synaptic signaling| |cellular divalent inorganic cation homeostasis| |positive regulation of neurogenesis| |response to peptide| |regulation of ion transmembrane transport| |immune response-regulating cell surface receptor signaling pathway| |negative regulation of transport| |neutrophil degranulation| |blood vessel development| |regulation of cell morphogenesis| |divalent inorganic cation homeostasis| |centrosome| |neutrophil activation involved in immune response| |skeletal system development| |regulation of neuron projection development| |neutrophil mediated immunity| |inflammatory response| |neutrophil activation| |cell-cell adhesion| |granulocyte activation| |transmembrane receptor protein tyrosine kinase signaling pathway| |vasculature development| |leukocyte degranulation| |regulation of protein serine/threonine kinase activity| |cardiovascular system development| |myeloid leukocyte mediated immunity| |myeloid cell activation involved in immune response| |heart development| |peptide metabolic process| |positive regulation of protein kinase activity| |positive regulation of nervous system development| |regulation of cellular protein localization| |positive regulation of cell development| |positive regulation of MAPK cascade| |sensory organ development| |cell junction| |regulation of vesicle-mediated transport| |cell population proliferation| |hemopoiesis| |cellular metal ion homeostasis| |negative regulation of phosphate metabolic process| |negative regulation of phosphorus metabolic process| |inorganic cation transmembrane transport| |immune response-activating signal transduction| |regulation of transmembrane transport| |tissue morphogenesis| |embryonic morphogenesis| |behavior| |positive regulation of kinase activity| |organelle localization| |myeloid leukocyte activation| |negative regulation of protein modification process| |protein-containing complex| |immune response-regulating signaling pathway| |cellular response to organonitrogen compound| |hematopoietic or lymphoid organ development| |cation transmembrane transport| |cell surface| |carbohydrate derivative biosynthetic process| |Golgi membrane| |metal ion homeostasis| |leukocyte activation involved in immune response| |cell activation involved in immune response| |activation of immune response| |chordate embryonic development| |cellular cation homeostasis| |metal ion transport| |positive regulation of apoptotic process| |cellular ion homeostasis| |inorganic ion transmembrane transport| |immune system development| |positive regulation of programmed cell death| |embryo development ending in birth or egg hatching| |tube morphogenesis| |positive regulation of transferase activity| |regulation of neuron differentiation| |cellular response to nitrogen compound| |regulation of cytokine production| |regulation of plasma membrane bounded cell projection organization| |positive regulation of cell death| |regulation of ion transport| |regulated exocytosis| |negative regulation of cellular component organization| |regulation of protein transport| |cation homeostasis| |regulation of cell projection organization| |negative regulation of cell differentiation| |enzyme linked receptor protein signaling pathway| |inorganic ion homeostasis| |regulation of proteolysis| |regulation of peptide transport| |brain development| |cellular chemical homeostasis| |regulation of establishment of protein localization| |regulation of MAPK cascade| |organelle assembly| |leukocyte mediated immunity| |cellular response to DNA damage stimulus| |head development| |ion homeostasis| |cellular amide metabolic process| |negative regulation of catalytic activity| |exocytosis| |regulation of protein kinase activity| |neuron development| |regulation of neurogenesis| |cation transport| |regulation of cellular catabolic process| |tube development| |negative regulation of transcription by RNA polymerase II| |positive regulation of immune response| |circulatory system development| |regulation of kinase activity| |negative regulation of apoptotic process| |anatomical structure formation involved in morphogenesis| |cellular homeostasis| |negative regulation of programmed cell death| |regulation of cellular localization| |apoptotic process| |regulation of nervous system development| |leukocyte activation| |cell adhesion| |regulation of cell development| |biological adhesion| |endoplasmic reticulum membrane| |negative regulation of developmental process| |ion transmembrane transport| |animal organ morphogenesis| |cell migration| |positive regulation of cell differentiation| |regulation of transferase activity| |embryo development| |central nervous system development| |Golgi apparatus| |positive regulation of transport| |regulation of catabolic process| |negative regulation of cell death| |response to organonitrogen compound| |secretion by cell| |neuron differentiation| |endoplasmic reticulum| |positive regulation of protein phosphorylation| |positive regulation of intracellular signal transduction| |carbohydrate derivative metabolic process| |regulation of protein localization| |negative regulation of cellular protein metabolic process| |export from cell| |programmed cell death| |cellular response to oxygen-containing compound| |positive regulation of phosphorylation| |regulation of anatomical structure morphogenesis| |cell activation| |cell motility| |localization of cell| |response to nitrogen compound| |cell death| |immune effector process| |negative regulation of protein metabolic process| |chemical homeostasis| |epithelium development| |cell-cell signaling| |plasma membrane bounded cell projection organization| |secretion| |positive regulation of phosphate metabolic process| |positive regulation of phosphorus metabolic process| |negative regulation of molecular function| |regulation of immune response| |positive regulation of immune system process| |cell projection organization| |negative regulation of transcription, DNA-templated| |negative regulation of multicellular organismal process| |positive regulation of cellular component organization| |cellular response to endogenous stimulus| |positive regulation of protein modification process| |negative regulation of nucleic acid-templated transcription| |negative regulation of RNA biosynthetic process| |mitochondrion| |negative regulation of signal transduction| |proteolysis| |transmembrane transport| |locomotion| |negative regulation of RNA metabolic process| |defense response| |negative regulation of cell communication| |negative regulation of signaling| |positive regulation of developmental process| |ion transport| |nervous system process| |negative regulation of cellular macromolecule biosynthetic process| |integral component of plasma membrane| |organonitrogen compound biosynthetic process| |positive regulation of catalytic activity| |negative regulation of nucleobase-containing compound metabolic process| |regulation of protein phosphorylation| |negative regulation of macromolecule biosynthetic process| |response to endogenous stimulus| |protein transport| |negative regulation of cellular biosynthetic process| |generation of neurons| |peptide transport| |positive regulation of transcription, DNA-templated| |regulation of apoptotic process| |negative regulation of biosynthetic process| |movement of cell or subcellular component| |response to oxygen-containing compound| |regulation of programmed cell death| |amide transport| |regulation of phosphorylation| |positive regulation of cellular protein metabolic process| |establishment of protein localization| |negative regulation of response to stimulus| |neurogenesis| |positive regulation of nucleic acid-templated transcription| |positive regulation of RNA biosynthetic process| |homeostatic process| |cell development| |regulation of immune system process| |positive regulation of signal transduction| |regulation of cell death| |intracellular signal transduction| |cellular response to stress| |positive regulation of protein metabolic process| |cellular macromolecule biosynthetic process| |negative regulation of gene expression| |positive regulation of RNA metabolic process| |positive regulation of multicellular organismal process| |tissue development| |macromolecule biosynthetic process| |positive regulation of molecular function| |regulation of phosphate metabolic process| |regulation of phosphorus metabolic process| |cellular catabolic process| |regulation of cell differentiation| |positive regulation of cell communication| |positive regulation of signaling| |regulation of intracellular signal transduction| |establishment of localization in cell| |regulation of protein modification process| |nitrogen compound transport| |regulation of transport| |immune response| |positive regulation of nucleobase-containing compound metabolic process| |positive regulation of macromolecule biosynthetic process| |vesicle-mediated transport| |system process| |positive regulation of cellular biosynthetic process| |positive regulation of gene expression| |membrane| |gene expression| |positive regulation of biosynthetic process| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp472|CI-1040 9.5μM R08 exp472]]|-1.8| |[[:results:exp321|ABT-702 5μM plus Deferoxamine 11μM R07 exp321]]|-1.78| |[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|-1.74| |[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|1.72| |[[:results:exp41|BI-2536 0.001μM R01 exp41]]|2.01| No correlation found to any other genes in chemogenomics. Global Fraction of Cell Lines Where Essential: 2/739 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/26| |breast|0/33| |central nervous system|0/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|0/16| |kidney|0/21| |liver|0/20| |lung|0/75| |lymphocyte|0/16| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/9| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 3312 * **Expression level (log2 read counts)**: 5.86 {{:chemogenomics:nalm6 dist.png?nolink |}}