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FLASH GENE
Symbol PSEN2 contributors: mct - updated : 13-06-2017
HGNC name presenilin 2 (Alzheimer disease 4)
HGNC id 9509
DNA
TYPE functioning gene
STRUCTURE 26.49 kb     11 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Map cen - D1S271E - PSEN2 - D1S644 - D1S2415 - qter
RNA
TRANSCRIPTS type messenger
text alternatively spliced, lacking exon 5, a third transcript of 2.8kb (PMID: 7638621)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
13 - 2299 50 447 heart, brain, placenta, liver, skeletal muscle, kidney 1998 9602061
lacks 3 nucleotides when compared to transcript variant 1 due to the use of an alternative splice acceptor sequence in exon 10
13 - 2302 50.1 448 - 1998 9602061
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Endocrinepancreas    
 parathyroid   highly
Lymphoid/Immunespleen   highly
Nervousbrain    
Reproductivemale systemprostate  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialsecretoryglandularendocrine 
Epithelialsecretoryglandularexocrine 
Muscularstriatumcardiac  
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • eight transmembrane segments (8TM) with cytoplasmic N (NTF) and C terminal,(CTF) fragments
  • a large cytoplasmic hydrophilic loop between transmembrane segments 6 and 7
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to C.elegans SPE-4
    intraspecies homolog to PSEN1 (highly)
    Homologene
    FAMILY
  • presenilin family
    • CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,chromatin/chromosome
    intracellular,nuclear envelope
    text
  • integral membrane protein
  • expressed in mitochondria-associated membranes (MAM) - a specialized subcompartment of the endoplasmic reticulum (ER) involved in lipid metabolism and calcium homeostasis that physically connects ER to mitochondria
    • basic FUNCTION
  • interacting with Rab11 and maybe involved in APP vesicular trafficking to the right compartment for activity, as well as processing of APP molecules (potential gamma secretase activity)
  • regulator of intracellular calcium homeostasis, controlling the alpha secretase derived product APP alpha
  • essential components of the gamma-secretase complex, which cleaves APP to affect Abeta processing
  • play a key role in the control of Ca2+ concentration within the endoplasmic reticulum (ER)
  • PSEN1, PSEN2 are novel substrates for TRAF6-mediated K63-linked ubiquitination and ubiquitination of presenilins by TRAF6 increases presenilin holoprotein levels and reduced TRAF6 ubiquitination of presenilins results in reduction of calcium release from the endoplasmic reticulum
  • PSEN1, PSEN2 regulates calcium homeostasis and synaptic function via ryanodine receptor (RyR), suggesting that disruption of intracellular calcium homeostasis may be an early pathogenic event leading to presynaptic dysfunction in Alzheimer disease
  • PSEN1, PSEN2 encode the major component of gamma-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-beta peptides
  • PSEN1, PSEN2 regulate calcium homeostasis in the endoplasmic reticulum, and dysregulation of intracellular calcium has been implicated in the pathogenesis of Alzheimer disease
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    gamma-secretase-dependent signaling pathway
    a component
  • forming a multimeric complex with catenin beta (CTNNB1)
  • PSEN1 or PSEN2, nicastrin (NCSTN), anterior pharynx-defective 1 (APH1A), and PSENEN have been considered the minimal essential subunits required to form an active gamma-secretase complex
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FHL2
  • sorcin
  • inhibitors of gamma secretase (to block amyloid beta protein)
  • forming a stable complex with beta-amyloid precursor protein
  • PRKN differently regulates PSEN1 and PSEN2 functions by direct control of their promoter transcription
  • PSEN2-ARF4 trafficking axis modulates NOTCH1 signaling during epidermal differentiation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AD4 , CMD1V
    related resource Alzheimer Disease Mutation Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in dilated cardiomyopathy, mild form, associated or not to AD
    constitutional     --over  
    in PS2 level augment the efficacy of Ca2+ transfer from the ER to the mitochondria
    Susceptibility to Alzheimer disease, sporadic and familial cases
    Variant & Polymorphism other association with a PSEN2 splice variant, lacking exon 5 in Alzheimer disease
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    an increase in ER–mitochondria tethering may mitigate the energetic defect linked to partial ER Ca2+ depletion caused by PSEN2 mutants, thus contributing to the milder phenotype of Azheimer disease cases linked to PSEN2 mutations
    ANIMAL & CELL MODELS