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PSEN2 Gene

protein-coding   GIFtS: 72
GCID: GC01P227058

Presenilin 2

(Previous name: Alzheimer disease 4)
(Previous symbol: AD4)
  See PSEN2-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Presenilin 21 2     PS22 3
AD41 2 3 5     STM-22 3
STM22 3 5     CMD1V2 5
Alzheimer Disease 41 2     AD3L2
AD3LP2 3     presenilin-22
AD52 3     EC 3.4.23.-3
E5-12 3     PSNL23
PS-22 3     EC 3.4.238

External Ids:    HGNC: 95091   Entrez Gene: 56642   Ensembl: ENSG000001438017   OMIM: 6007595   UniProtKB: P498103   

Export aliases for PSEN2 gene to outside databases

Previous GC identifers: GC01P225587 GC01P222803 GC01P223443 GC01P224033 GC01P224032 GC01P223365 GC01P225124 GC01P197575


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PSEN2 Gene:
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins
(PSEN1 or PSEN2) or 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 act are protease enzymes. Two
alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified. (provided by
RefSeq, Jul 2008)

GeneCards Summary for PSEN2 Gene:
PSEN2 (presenilin 2) is a protein-coding gene. Diseases associated with PSEN2 include alzheimer disease type 4, and alzheimer disease type 1. GO annotations related to this gene include endopeptidase activity and aspartic-type endopeptidase activity. An important paralog of this gene is PSEN1.

UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810
Function: Probable 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 (beta-amyloid precursor
protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role
in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in
the cytoplasmic partitioning of proteins

summary for PSEN2 Gene:
Secretases are a group of enzymes involved in the proteolytic cleavage of amyloid precursor protein (APP).
There are three types of secretases, alpha-secretase, beta-secretase and gamma-secretase. gamma-Secretase is
a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is
itself an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1
and PEN-2. Presenilin is an aspartic protease and the catalytic subunit of the complex. There are two
important substrates of gamma-secretase; amyloid precursor protein (APP) and Notch. gamma-secretase can
cleave several sites within APP, and the most common products are Abeta40 and Abeta42. Abeta42 is
fibrillogenic and associated with disease states, notably Alzheimer's disease. gamma-Secretase catalyzes the
second step in Notch protein cleavage. gamma-Secretase cleaves within the transmembrane domain of Notch,
releasing the intracellular domain (Nbeta) into the cytoplasm. Nbeta moves to the nucleus where it can
regulate gene expression by activating the transcription factor CSL. This gamma-secretase-Notch signaling
pathway has a role in promoting angiogenesis in the embryo and wound healing in the adult.

Gene Wiki entry for PSEN2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000001.10  NT_167186.2  NC_018912.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the PSEN2 gene promoter:
         SRF   AREB6   RORalpha1   p53   SRF (504 AA)   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidPSEN2 promoter sequence
   Search Chromatin IP Primers for PSEN2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PSEN2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1q42.13   Ensembl cytogenetic band:  1q42.13   HGNC cytogenetic band: 1q42.13

PSEN2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PSEN2 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01P227058:  view genomic region     (about GC identifiers)

Start:
227,057,885 bp from pter      End:
227,083,806 bp from pter
Size:
25,922 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810 (See protein sequence)
Recommended Name: Presenilin-2  
Size: 448 amino acids; 50140 Da
Subunit: Interacts with DOCK3 (By similarity). Homodimer. Component of the gamma-secretase complex, a complex
composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such
minimal complex is sufficient for secretase activity, although other components may exist. Interacts with
HERPUD1, FLNA, FLNB and PARL
Secondary accessions: A8K8D4 B1AP21 Q96P32
Alternative splicing: 3 isoforms:  P49810-1   P49810-2   P49810-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for PSEN2: NX_P49810

Explore proteomics data for PSEN2 at MOPED

Post-translational modifications: 

  • Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments1
  • Phosphorylated on serine residues1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for PSEN2 (P49810) (see all 24)
     IHWKGPL  VPVTLCM  EEDPDRY  LQQAYLI 


    See PSEN2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000438.2  NP_036618.2  

    ENSEMBL proteins: 
     ENSP00000429036   ENSP00000355747   ENSP00000429682   ENSP00000403737   ENSP00000427912  
     ENSP00000355746   ENSP00000430647   ENSP00000427806   ENSP00000375745   ENSP00000339860  
    Reactome Protein details: P49810

    PSEN2 Human Recombinant Protein Products:

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    Novus Biologicals PSEN2 Protein
    Novus Biologicals PSEN2 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for PSEN2 

    PSEN2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of PSEN2
    R&D Systems Antibodies for PSEN2 (Presenilin-2)
    Cell Signaling Technology (CST) Antibodies for PSEN2 
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    OriGene Custom Antibody Services for PSEN2
    Novus Biologicals PSEN2 Antibodies
    Abcam antibodies for PSEN2 (Q9NZ42, P49810)
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for PSEN2
    LSBio Antibodies in human, mouse, rat for PSEN2

    PSEN2 Assay Products:

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    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for PSEN2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR006639 Preselin/SPP
     IPR001108 Peptidase_A22A
     IPR001493 Pept_A22A_PS2

    Graphical View of Domain Structure for InterPro Entry P49810

    ProtoNet protein and cluster: P49810

    2 Blocks protein domains:
    IPB001493 Presenilin 2 signature
    IPB006639 Presenilin signal peptide peptidase


    UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810
    Domain: The PAL motif is required for normal active site conformation (By similarity)
    Similarity: Belongs to the peptidase A22A family


    Find genes that share domains with PSEN2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: PSN2_HUMAN, P49810
    Function: Probable 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 (beta-amyloid precursor
    protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role
    in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in
    the cytoplasmic partitioning of proteins

         Genatlas biochemistry entry for PSEN2:
    presenilin 2,forming a multimeric complex with catenin beta (CTNNB1),expressed in several parts of the brain in
    cardiac and skeletal muscle,in pancreas,predominantly located in intracellular membranous organelles such as
    nuclear envelope,endoplasmic reticulum and Golgi apparatus with 80% homology to S182 (C. elegans Sel-12
    gene),interacting with Rab11 and may be involved in APP vesicular trafficking to the right compartment for
    activity,homologous to C elegans SPE-4,controlling the alpha secretase derived product APP alpha

         Enzyme Numbers (IUBMB): EC 3.4.232 EC 3.4.23.-1

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004175endopeptidase activity IBA--
    GO:0004190aspartic-type endopeptidase activity IEA--
    GO:0005515protein binding IPI10366599
         
    Find genes that share ontologies with PSEN2           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for PSEN2:
     Increased cell death in HCC-19 

         Selected MGI mutant phenotypes (inferred from 3 alleles(MGI details for Psen2) (see all 19):
     behavior/neurological  cardiovascular system  cellular  craniofacial  digestive/alimentary 
     embryogenesis  endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  mortality/aging  nervous system 

    Find genes that share phenotypes with PSEN2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for PSEN2: Psen2tm1Haa Psen2tm1Bdes Psen2tm1Ber

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PSEN2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for PSEN2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PSEN2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PSEN2

    miRNA
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    5 qRT-PCR Assays for microRNAs that regulate PSEN2:
    hsa-miR-548a-3p hsa-miR-183 hsa-miR-548e hsa-miR-4299 hsa-miR-1284
    SwitchGear 3'UTR luciferase reporter plasmidPSEN2 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Predesigned siRNA for gene silencing in human, mouse, rat PSEN2

    Gene Editing
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    DNA2.0 Custom Protein Engineering Service for PSEN2

    Clone
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    OriGene clones in human, mouse for PSEN2 (see all 12)
    OriGene ORF clones in mouse, rat for PSEN2
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    GenScript: all cDNA clones in your preferred vector (see all 2): PSEN2 (NM_000447)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PSEN2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PSEN2

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    Flow Cytometry
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    eBioscience FlowRNA Probe Sets ( VA6-13077) for PSEN2 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    PSN2_HUMAN, P49810: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane;
    Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    endoplasmic reticulum5
    golgi apparatus5
    nucleus5
    plasma membrane4
    lysosome3
    mitochondrion3
    vacuole3
    cytosol2
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane IEA--
    GO:0000776kinetochore IDA9298903
    GO:0005637nuclear inner membrane IDA9298903
    GO:0005743mitochondrial inner membrane IBA--
    GO:0005765lysosomal membrane IBA--

    Find genes that share ontologies with PSEN2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for PSEN2 About   (see all 22)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Notch signaling pathway (KEGG)
    Notch signaling pathway0.84
    Notch Signaling0.30
    Notch Signaling Pathway0.84
    Signaling by NOTCH30.00
    Delta-Notch Signaling Pathway0.33
    Signaling by NOTCH40.00
    2Alzheimer's disease
    Alzheimers Disease0.44
    Alzheimer's disease0.44
    3Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants0.79
    Signaling by NOTCH1 HD Domain Mutants in Cancer0.79
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Constitutive Signaling by NOTCH1 PEST Domain Mutants0.79
    Signaling by NOTCH1 in Cancer0.79
    Signaling by NOTCH1 t(7;9)(NOTCH1-M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH10.79
    FBXW7 Mutants and NOTCH1 in Cancer0.79
    4p75 NTR receptor-mediated signalling
    p75 NTR receptor-mediated signalling0.74
    Regulated proteolysis of p75NTR0.00
    Cell death signalling via NRAGE, NRIF and NADE0.74
    NRIF signals cell death from the nucleus0.00
    5Signaling by NOTCH2
    NOTCH2 Activation and Transmission of Signal to the Nucleus0.67
    Activated NOTCH1 Transmits Signal to the Nucleus0.61
    Signaling by NOTCH20.67


    Find genes that share SuperPaths with PSEN2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 R&D Systems Pathways for PSEN2
        A-beta Plaque Formation & APP Metabolism
    Notch Signaling Pathways

    5 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for PSEN2
        Notch Signaling
    Molecular Mechanisms of Cancer
    Alzheimers Disease Pathway
    Presenilin-Mediated Signaling
    ErbB4 Pathway

    2 Cell Signaling Technology (CST) Pathways for PSEN2
        Wnt / Hedgehog / Notch
    Neuroscience

    1 Tocris Bioscience Pathway for PSEN2
        Notch Pathway

    3 GeneGo (Thomson Reuters) Pathways for PSEN2
        Development NOTCH1-mediated pathway for NF-KB activity modulation
    Development Notch Signaling Pathway
    Development MAG-dependent inhibition of neurite outgrowth

    4 BioSystems Pathways for PSEN2
        Notch Signaling Pathway
    Delta-Notch Signaling Pathway
    Alzheimers Disease
    LKB1 signaling events

    Selected Reactome Pathways for PSEN2 (see all 9)
        Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
    NRIF signals cell death from the nucleus
    Regulated proteolysis of p75NTR
    NOTCH2 Activation and Transmission of Signal to the Nucleus
    Signaling by NOTCH4


    3 Kegg Pathways  (Kegg details for PSEN2):
        Notch signaling pathway
    Neurotrophin signaling pathway
    Alzheimer's disease

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PSEN2: 
              Parkinson's Disease in human mouse rat
              Stem Cell Signaling in human mouse rat
              Alzheimer's Disease in human mouse rat
              Notch Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for PSEN2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for PSEN2 (P498101, 2, 3 ENSP000003557474) via UniProtKB, MINT, STRING, and/or I2D (see all 104)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CIB1Q998282, 3, ENSP000003338734MINT-15561 MINT-15560 MINT-15562 I2D: score=5 STRING: ENSP00000333873
    UBQLN1Q9UMX02, 3, ENSP000003655764MINT-17616 MINT-17615 MINT-17617 I2D: score=3 STRING: ENSP00000365576
    FLNBO753692, 3, ENSP000002959564MINT-14380 MINT-14379 I2D: score=4 STRING: ENSP00000295956
    DYNC1H1Q142041, 3EBI-2010251,EBI-356015 I2D: score=1 
    ECSITQ9BQ951, 3EBI-2010251,EBI-712452 I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 49):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IEA--
    GO:0001708cell fate specification IEA--
    GO:0001756somitogenesis IEA--
    GO:0001933negative regulation of protein phosphorylation IEA--
    GO:0001942hair follicle development ----

    Find genes that share ontologies with PSEN2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for PSEN2 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    MRK 560gamma-secretase inhibitor; attenuates amyloid plaque deposition[677772-84-8]
    JLK 6Inhibitor of gamma-secretase-mediated betaAPP processing[62252-26-0]
    L-685,458 Potent and selective gamma-secretase inhibitor[292632-98-5]
    Begacestatgamma-secretase inhibitor; lowers Abeta40 and Abeta42 levels[769169-27-9]
    DAPTgamma-secretase inhibitor[208255-80-5]

    Selected Novoseek inferred chemical compound relationships for PSEN2 gene (see all 44)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    s-182 84.1 2 9118312 (1), 9067452 (1)
    estrogen 70.8 127 12021387 (5), 12403846 (5), 19460860 (2), 10517346 (2) (see all 76)
    ab-42 69.1 2 11259376 (1)
    moxestrol 62.5 1 14617632 (1)
    progesterone 61.2 60 19460860 (2), 10517346 (2), 10917137 (2), 7927897 (2) (see all 46)
    4-hydroxytamoxifen 53.2 3 16840538 (1), 18827493 (1), 8344199 (1)
    tamoxifen 47.7 14 16166331 (3), 9366498 (3), 7812959 (2), 8932874 (1) (see all 8)
    estradiol 38.8 16 17068199 (2), 18644870 (2), 1485091 (1), 19041697 (1) (see all 11)
    fulvestrant 34.2 5 8932874 (1), 16533599 (1), 17936617 (1)
    lactacystin 34.1 2 9110991 (1)



    Find genes that share compounds with PSEN2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for PSEN2 gene (2 alternative transcripts): 
    NM_000447.2  NM_012486.2  

    Unigene Cluster for PSEN2:

    Presenilin 2 (Alzheimer disease 4)
    Hs.25363  [show with all ESTs]
    Unigene Representative Sequence: BC006365
    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000524196 ENST00000366783(uc009xeo.1 uc009xep.1 uc001hqk.2)
    ENST00000495488 ENST00000422240 ENST00000521431 ENST00000460775 ENST00000366782
    ENST00000496965 ENST00000472139 ENST00000487450 ENST00000471728 ENST00000391872
    ENST00000340188
    miRNA
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    hsa-miR-548a-3p hsa-miR-183 hsa-miR-548e hsa-miR-4299 hsa-miR-1284
    SwitchGear 3'UTR luciferase reporter plasmidPSEN2 3' UTR sequence
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    GenScript: all cDNA clones in your preferred vector (see all 2): PSEN2 (NM_000447)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PSEN2
    Primer
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    Additional mRNA sequence: 

    AF416718.1 AK292299.1 AK301143.1 BC006365.2 BT006984.1 L43964.1 L44577.1 U34349.1 

    11 DOTS entries:

    DT.451603  DT.100791211  DT.101980870  DT.100791210  DT.97802189  DT.121427797  DT.97771435  DT.95375318 
    DT.100693380  DT.40110274  DT.97780884 

    Selected AceView cDNA sequences (see all 173):

    AA993681 AL047795 AI924549 BX093003 CD672922 BI761633 AI675803 CR594395 
    AI142959 CA310542 AI093291 AI474673 CD358381 AI927349 CD512951 AI340021 
    CD513489 CD673541 CK823284 AL703261 AI168440 AU132195 BQ919087 AW995897 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for PSEN2 (see all 8)    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b
    SP1:                                      -                             -                                                                     
    SP2:                                      -                             -                                                                     
    SP3:                                                                                                                                          
    SP4:                                      -     -     -     -     -     -     -     -                                                         
    SP5:                                      -                                                                                                   


    ECgene alternative splicing isoforms for PSEN2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    PSEN2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATGTCCTTGT
    PSEN2 Expression
    About this image


    PSEN2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 11) fully expand
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Cerebellum
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Neural Tube (Nervous System)
             Metencephalon
     
     Cartilage (Muscoskeletal System)
             Intervertebral Disc Nucleus Pulposus Cells Nucleus Pulposus
    PSEN2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PSEN2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.25363

    UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810
    Tissue specificity: Isoform 1 is seen in the placenta, skeletal muscle and heart while isoform 2 is seen in the
    heart, brain, placenta, liver, skeletal muscle and kidney

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PSEN2: 
              Parkinson's Disease in human mouse rat
              Stem Cell Signaling in human mouse rat
              Alzheimer's Disease in human mouse rat
              Notch Signaling Pathway in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for PSEN2 gene from Selected species (see all 19)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Psen21 , 5 presenilin 21, 5 89.58(n)1
    95.98(a)1
      1 (84.19 cM)5
    191651  NM_001128605.11  NP_001122077.11 
     1802270045 
    chicken
    (Gallus gallus)
    Aves PSEN21 presenilin 2 (Alzheimer disease 4) 72.02(n)
    79.53(a)
      374188  NM_204302.1  NP_989633.1 
    lizard
    (Anolis carolinensis)
    Reptilia PSEN26
    presenilin 2 (Alzheimer disease 4)
    75(a)
    1 ↔ 1
    1(251060893-251076684)
    African clawed frog
    (Xenopus laevis)
    Amphibia D84428.12   -- 77.17(n)    D84428.1 
    zebrafish
    (Danio rerio)
    Actinopterygii AJ271795.12   -- 80.28(n)   58026  AJ271795.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Psn1 Presenilin 58.58(n)
    57.21(a)
      40260  NM_001144516.2  NP_001137988.1 
    worm
    (Caenorhabditis elegans)
    Secernentea sel-123 Expression: all stages 53(a)
    (best of 2)
      X(951181-953466)   --
    rice
    (Oryza sativa)
    Liliopsida Os.114482 Oryza sativa (japonica cultivar-group) cDNA clone0 more 74.42(n)    AK106403.1 


    ENSEMBL Gene Tree for PSEN2 (if available)
    TreeFam Gene Tree for PSEN2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for PSEN2 gene
    PSEN12  
    1 SIMAP similar gene for PSEN2 using alignment to 8 protein entries:     PSN2_HUMAN (see all proteins):
    PSEN1

    Find genes that share paralogs with PSEN2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for PSEN2 (see all 852)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs289363791,2,,4
    CAlzheimer disease 4 (AD4)4 pathogenic1233871984(+) CGCTCA/GTGGCC 4 M V mis1 ese30--------
    VAR_0092154
    Alzheimer disease 4 (AD4)4--see VAR_0092152 M I mis40--------
    VAR_0064624
    Alzheimer disease 4 (AD4)4--see VAR_0064622 N I mis40--------
    VAR_0092144
    Alzheimer disease 4 (AD4)4--see VAR_0092142 T P mis40--------
    VAR_0079584
    Alzheimer disease 4 (AD4)4--see VAR_0079582 V I mis40--------
    rs637500481,2
    Cpathogenic1233866821(+) CGGAGC/TGAAGC 4 A V mis10--------
    rs637498511,2
    Cpathogenic1233868549(+) TCTACA/CCGCCA 4 T P mis10--------
    rs289363801,2
    Cpathogenic1233868550(+) CTACAC/GGCCAT 4 T R mis1 ese30--------
    rs637501971,2,,4
    C,Fpathogenic1233868574(+) ACCCTC/TGGTGG 4 S L mis12Minor allele frequency- T:0.00NA EU 5857
    rs637502151,2
    Cpathogenic1233868607(+) GCTGAA/TCACCC 4 N I mis10--------

    HapMap Linkage Disequilibrium report for PSEN2 (227057885 - 227083806 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for PSEN2:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv4766CNV Loss18451855

    Human Gene Mutation Database (HGMD): PSEN2
    Locus Specific Mutation Databases (LSDB): PSEN2

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing PSEN2
    DNA2.0 Custom Variant and Variant Library Synthesis for PSEN2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600759   
    OMIM disorders: 606889  613697  
    UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810
  • Alzheimer disease 4 (AD4) [MIM:606889]: A familial early-onset form of Alzheimer disease. Alzheimer
    disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and
    deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques
    and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42
    peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase
    processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from
    APP, are also implicated in neuronal death. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Cardiomyopathy, dilated 1V (CMD1V) [MIM:613697]: A disorder characterized by ventricular dilation and
    impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of
    premature death. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 10 diseases for PSEN2:    
    About MalaCards
    alzheimer disease type 4    alzheimer disease type 1    psen2-related dilated cardiomyopathy    cardiomyopathy, dilated, 1v
    familial idiopathic basal ganglia calcification    alzheimer disease type 2    alzheimer's disease    lewy body dementia
    cardiomyopathy, dilated, 1w    breast cancer

    2 diseases from the University of Copenhagen DISEASES database for PSEN2:
    Alzheimer's disease     Frontotemporal dementia

    Find genes that share disorders with PSEN2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for PSEN2 gene (see all 35)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    alzheimers disease 89.2 344 12925374 (4), 9694871 (3), 16233903 (3), 8952521 (2) (see all 99)
    early onset alzheimer disease 84.9 8 9602061 (1), 10069575 (1), 12354302 (1), 12629906 (1) (see all 6)
    senile plaques 75.1 11 9050898 (1), 10069575 (1), 9450781 (1), 11816789 (1) (see all 11)
    neurofibrillary tangles 67.4 9 8952521 (1), 9450781 (1), 12581338 (1), 9683997 (1) (see all 6)
    dementia 63 14 11810290 (1), 14503010 (1), 18300294 (1), 18587238 (1) (see all 13)
    breast cancer 62.6 61 16503540 (5), 9472649 (5), 8318427 (4), 14659340 (3) (see all 32)
    late onset alzheimer disease 62.5 2 10430506 (1)
    amyloid deposition 58.6 2 10468510 (1)
    frontotemporal dementia 57 2 19012865 (1), 18314228 (1)
    neurodegenerative diseases 52.3 1 19834068 (1)

    GeneTests: PSEN2
    GeneReviews: PSEN2
    Genetic Association Database (GAD): PSEN2
    Human Genome Epidemiology (HuGE) Navigator: PSEN2 (28 documents)

    Export disorders for PSEN2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for PSEN2 gene, integrated from 10 sources (see all 593):
    (articles sorted by number of sources associating them with PSEN2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease. (PubMed id 12925374)1, 4, 9 Ezquerra M....Oliva R. (Arch. Neurol. 2003)
    2. Regulatory region variability in the human presenilin-2 (PSEN2) gene: potential contribution to the gene activity and risk for AD. (PubMed id 12232783)1, 4, 9 Riazanskaia N....Rogaev E. (Mol. Psychiatry 2002)
    3. Two polymorphisms of presenilin-2 gene (PSEN2) 5' regulatory region are not associated with Alzheimer's disease (AD) in the Polish population. (PubMed id 18087668)1, 4, 9 Gacia M....Barcikowska M. (J Neural Transm 2008)
    4. The association of the regulatory region of the presenilin-2 gene with Alzheimer's disease in the Northern Han Chinese population. (PubMed id 17727891)1, 4, 9 Liu Z. and Jia J. (J. Neurol. Sci. 2008)
    5. A novel mutation in the predicted TM2 domain of the presenilin 2 gene in Spanish patient with late-onset Alzheimer's disease. (PubMed id 10732806)1, 2, 9 Lao J.I.... Cacabelos R. (Neurogenetics 1998)
    6. Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. (PubMed id 8574969)1, 2, 9 Kovacs D.M.... Wasco W. (Nat. Med. 1996)
    7. The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation. (PubMed id 10652302)1, 2, 9 Kimberly W.T.... Selkoe D.J. (J. Biol. Chem. 2000)
    8. Polymorphism of the regulatory region of the presenilin-2 gene in sporadic Alzheimer's disease: a case-control study. (PubMed id 16233903)1, 4, 9 Quan W....Maeda K. (J. Neurol. Sci. 2006)
    9. Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. (PubMed id 14769392)1, 4, 9 Zekanowski C....Barcikowska M. (Exp. Neurol. 2003)
    10. Presenilin mutations in Alzheimer's disease. (PubMed id 9521418)1, 2, 9 Cruts M. and van Broeckhoven C. (Hum. Mutat. 1998)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5664 HGNC: 9509 AceView: PSEN2 Ensembl:ENSG00000143801 euGenes: HUgn5664
    ECgene: PSEN2 Kegg: 5664 H-InvDB: PSEN2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for PSEN2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for PSEN2 Genetics and Cytogenetics in Oncology and Haematology
    Alzheimer Research Forumhttp://www.alzforum.org/res/com/mut/pre/default.asp
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=PSEN2[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for PSEN2 gene:
    Search GeneIP for patents involving PSEN2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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