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Gene Ontology Classifications
presenilin 1

Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Psen1. (This text reflects annotations as of Tuesday, May 26, 2015.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of May 1, 2008. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.
Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text based on GO annotations supported by structural data
Summary text for additional MGI annotations
  1. Annaert WG et al. (2001) Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron, 32:579-89. (PubMed:11719200)
  2. Baki L et al. (2004) PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J, 23:2586-96. (PubMed:15192701)
  3. Chan SL et al. (2002) Presenilin-1 mutations sensitize neurons to DNA damage-induced death by a mechanism involving perturbed calcium homeostasis and activation of calpains and caspase-12. Neurobiol Dis, 11:2-19. (PubMed:12460542)
  4. Chen F et al. (2003) Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain. J Biol Chem, 278:19974-9. (PubMed:12646573)
  5. De Strooper B et al. (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain [see comments] Nature, 398:518-22. (PubMed:10206645)
  6. Dong S et al. (2007) Environment enrichment rescues the neurodegenerative phenotypes in presenilins-deficient mice. Eur J Neurosci, 26:101-12. (PubMed:17614943)
  7. Donoviel DB et al. (1999) Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev, 13:2801-10. (PubMed:10557208)
  8. Esselens C et al. (2004) Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway. J Cell Biol, 166:1041-54. (PubMed:15452145)
  9. Feng R et al. (2001) Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron, 32:911-26. (PubMed:11738035)
  10. Feng R et al. (2004) Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2. Proc Natl Acad Sci U S A, 101:8162-7. (PubMed:15148382)
  11. Ferjentsik Z et al. (2009) Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet, 5:e1000662. (PubMed:19779553)
  12. Georgakopoulos A et al. (2006) Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling. EMBO J, 25:1242-52. (PubMed:16511561)
  13. Gowrishankar K et al. (2004) Release of a membrane-bound death domain by {gamma}-secretase processing of the p75NTR homolog NRADD. J Cell Sci, 117:4099-4111. (PubMed:15280425)
  14. Guo Q et al. (1999) Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. Proc Natl Acad Sci U S A, 96:4125-30. (PubMed:10097174)
  15. Handler M et al. (2000) Presenilin-1 regulates neuronal differentiation during neurogenesis. Development, 127:2593-606. (PubMed:10821758)
  16. Hartmann D et al. (1999) Presenilin-1 deficiency leads to loss of Cajal-Retzius neurons and cortical dysplasia similar to human type 2 lissencephaly. Curr Biol, 9:719-27. (PubMed:10421573)
  17. Hebert SS et al. (2004) Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol Dis, 17:260-72. (PubMed:15474363)
  18. Herms J et al. (2003) Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. J Biol Chem, 278:2484-9. (PubMed:12431992)
  19. Herreman A et al. (1999) Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc Natl Acad Sci U S A, 96:11872-7. (PubMed:10518543)
  20. Kamal A et al. (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature, 414:643-8. (PubMed:11740561)
  21. Kashiwa A et al. (2000) Isolation and characterization of novel presenilin binding protein. J Neurochem, 75:109-16. (PubMed:10854253)
  22. Kilb W et al. (2004) Altered morphological and electrophysiological properties of Cajal-Retzius cells in cerebral cortex of embryonic Presenilin-1 knockout mice. Eur J Neurosci, 20:2749-56. (PubMed:15548218)
  23. Kim JS et al. (2006) Presenilin-1 inhibits delta-catenin-induced cellular branching and promotes delta-catenin processing and turnover. Biochem Biophys Res Commun, 351:903-8. (PubMed:17097608)
  24. Kim MY et al. (2005) Presenilin acts as a positive regulator of basal level activity of ERK through the Raf-MEK1 signaling pathway. Biochem Biophys Res Commun, 332:609-13. (PubMed:15896720)
  25. Koizumi Ki et al. (2001) The role of presenilin 1 during somite segmentation. Development, 128:1391-402. (PubMed:11262239)
  26. Lai MT et al. (2003) Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities. J Biol Chem, 278:22475-81. (PubMed:12684521)
  27. Laky K et al. (2007) Presenilins regulate alphabeta T cell development by modulating TCR signaling. J Exp Med, 204:2115-29. (PubMed:17698590)
  28. Lee JH et al. (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell, 141:1146-58. (PubMed:20541250)
  29. Lee MK et al. (1996) Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J Neurosci, 16:7513-25. (PubMed:8922407)
  30. Leem JY et al. (2002) Presenilin 1 is required for maturation and cell surface accumulation of nicastrin. J Biol Chem, 277:19236-40. (PubMed:11943765)
  31. Li T et al. (2007) Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci, 27:10849-59. (PubMed:17913918)
  32. Liu Q et al. (2007) Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron, 56:66-78. (PubMed:17920016)
  33. Louvi A et al. (2004) Presenilin 1 in migration and morphogenesis in the central nervous system. Development, 131:3093-105. (PubMed:15163631)
  34. Ma G et al. (2005) APH-1a is the principal mammalian APH-1 isoform present in gamma-secretase complexes during embryonic development. J Neurosci, 25:192-8. (PubMed:15634781)
  35. Marambaud P et al. (2002) A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J, 21:1948-56. (PubMed:11953314)
  36. Mattson MP et al. (2000) Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture: involvement of perturbed calcium homeostasis. J Neurosci, 20:1358-64. (PubMed:10662826)
  37. Mizuguchi R et al. (2006) Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Nat Neurosci, 9:770-8. (PubMed:16715081)
  38. Mohmmad Abdul H et al. (2006) Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for J Neurochem, 96:1322-35. (PubMed:16478525)
  39. Morton RA et al. (2002) Impairment in hippocampal long-term potentiation in mice under-expressing the Alzheimer's disease related gene presenilin-1. Neurosci Lett, 319:37-40. (PubMed:11814648)
  40. Nakajima M et al. (2004) Presenilin 1 is essential for cardiac morphogenesis. Dev Dyn, 230:795-9. (PubMed:15254914)
  41. Nelson O et al. (2007) Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. J Clin Invest, 117:1230-9. (PubMed:17431506)
  42. Pan Y et al. (2004) gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell, 7:731-43. (PubMed:15525534)
  43. Pan Y et al. (2005) Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis. Dev Biol, 286:472-82. (PubMed:16169548)
  44. Payette DJ et al. (2007) Reduction in CHT1-mediated choline uptake in primary neurons from presenilin-1 M146V mutant knock-in mice. Brain Res, 1135:12-21. (PubMed:17196556)
  45. Pigino G et al. (2003) Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport. J Neurosci, 23:4499-508. (PubMed:12805290)
  46. Qyang Y et al. (2004) Myeloproliferative disease in mice with reduced presenilin gene dosage: effect of gamma-secretase blockage. Biochemistry, 43:5352-9. (PubMed:15122901)
  47. Rocher-Ros V et al. (2010) Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene, 29:2950-61. (PubMed:20208556)
  48. Satpathy AT et al. (2013) Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol, 14:937-48. (PubMed:23913046)
  49. Saura CA et al. (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron, 42:23-36. (PubMed:15066262)
  50. Shen J et al. (1997) Skeletal and CNS defects in Presenilin-1-deficient mice. Cell, 89:629-39. (PubMed:9160754)
  51. Six E et al. (2003) The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase. Proc Natl Acad Sci U S A, 100:7638-43. (PubMed:12794186)
  52. Stemmer N et al. (2013) Generation of amyloid-beta is reduced by the interaction of calreticulin with amyloid precursor protein, presenilin and nicastrin. PLoS One, 8:e61299. (PubMed:23585889)
  53. Suzuki Y et al. (2009) An alternative spliced mouse presenilin-2 mRNA encodes a novel gamma-secretase inhibitor. FEBS Lett, 583:1403-8. (PubMed:19376115)
  54. Teranishi Y et al. (2012) Erlin-2 is associated with active gamma-secretase in brain and affects amyloid beta-peptide production. Biochem Biophys Res Commun, 424:476-81. (PubMed:22771797)
  55. Vetrivel KS et al. (2005) Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem, 280:25892-900. (PubMed:15886206)
  56. Wen PH et al. (2005) Selective expression of presenilin 1 in neural progenitor cells rescues the cerebral hemorrhages and cortical lamination defects in presenilin 1-null mutant mice. Development, 132:3873-83. (PubMed:16079160)
  57. Wilson CA et al. (2004) Degradative organelles containing mislocalized {alpha}- and {beta}-synuclein proliferate in presenilin-1 null neurons. J Cell Biol, 165:335-346. (PubMed:15123735)
  58. Wong PC et al. (1997) Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature, 387:288-92. (PubMed:9153393)
  59. Wu J et al. (2011) Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent beta-amyloid generation. Cell, 147:615-28. (PubMed:22036569)
  60. Yang J et al. (2005) The ciliary rootlet interacts with kinesin light chains and may provide a scaffold for kinesin-1 vesicular cargos. Exp Cell Res, 309:379-89. (PubMed:16018997)
  61. Yang Y et al. (2004) Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake. J Neurochem, 88:1361-72. (PubMed:15009636)
  62. Yu H et al. (2001) App processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron, 31:713-26. (PubMed:11567612)
  63. Yuasa S et al. (2002) Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice. J Neurosci Res, 70:501-13. (PubMed:12391611)
  64. Zhang YW et al. (2007) Presenilin/{gamma}-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression. Proc Natl Acad Sci U S A, 104:10613-8. (PubMed:17556541)
  65. Zhao G et al. (2010) Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. J Neurosci, 30:1648-56. (PubMed:20130175)

Go Annotations in Tabular Form (Text View) (GO Graph)

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Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IAS Inferred from ancestral sequence
  IBA Inferred from biological aspect of ancestor
  IBD Inferred from biological aspect of descendant
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IKR Inferred from key residues
  IMP Inferred from mutant phenotype
  IMR Inferred from missing residues
  IPI Inferred from physical interaction
  IRD Inferred from rapid divergence
  ISS Inferred from sequence or structural similarity
  ISO Inferred from sequence orthology
  ISA Inferred from sequence alignment
  ISM Inferred from sequence model
  NAS Non-traceable author statement
  ND No biological data available
  RCA Reviewed computational analysis
  TAS Traceable author statement


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