PSEN1
Gene Information
- Official Symbol: PSEN1
- Official Name: presenilin 1
- Aliases and Previous Symbols: N/A
- Entrez ID: 5663
- UniProt: P49768
- Interactions: BioGRID
- PubMed articles: Open PubMed
- OMIM: 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}.
Pfam Domains GO Terms
Pfam Domains
| Presenilin |
GO Terms
| 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
Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Compound Hit
Most Correlated Genes in Chemogenomics
No correlation found to any other genes in chemogenomics.
Tissues where Essential in the Avana Dataset (DepMap 20Q1)
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
Expression Distribution
PSEN1 Expression in NALM6 Cells: 5.86
