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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

PSEN2 Gene

protein-coding   GIFtS: 73
GCID: GC01P227058

presenilin 2 (Alzheimer disease 4)


(Previous symbol: AD4)
 Explore 52 diseases affiliated with
PSEN2 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for PSEN2    

Aliases
for PSEN2 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Presenilin 2 (Alzheimer Disease 4)1 2     PS-22 3
AD41 2 3 5     STM-22 3
STM21 2 3 5     CMD1V2 5
PS21 2 3     Presenilin-21
AD3L1 2     EC 3.4.23.-3
AD3LP2 3     PSNL23
AD52 3     EC 3.4.238
E5-12 3     

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


Summaries
for PSEN2 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for PSEN2:
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)

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:
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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NC_018912.1  NT_167186.1  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the PSEN2 gene promoter:
         SRF   AREB6   RORalpha1   p53   SRF (504 AA)   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: PSEN2 promoter sequence
   Search SABiosciences Chromatin IP Primers for PSEN2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat PSEN2


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

Entrez Gene cytogenetic band: 1q31-q42   Ensembl cytogenetic band:  1q42.13   HGNC cytogenetic band: 1q31-q42

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

Proteins
for PSEN2 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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
Subcellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass
membrane protein
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

Post-translational modifications:

  • Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments1
  • Phosphorylated on serine residues1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P49810

    • 4/24 DME Specific Peptides for PSEN2 (P49810) (see all 24)
     IHWKGPL  VPVTLCM  EEDPDRY  LQQAYLI 

    PSEN2 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    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
    Human Recombinant Protein Products: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate: PSEN2
    OriGene Custom Protein Services for PSEN2 
    GenScript Custom Purified and Recombinant Proteins Services for PSEN2
    Novus Biologicals PSEN2 Protein
    Novus Biologicals PSEN2 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for PSEN2

    Gene Ontology (GO): 5/28 cellular component terms (GO ID links to tree view) (see all 28):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane IEA--
    GO:0000776kinetochore IDA9298903
    GO:0005622intracellular ----
    GO:0005624membrane fraction ----
    GO:0005637nuclear inner membrane IDA9298903


    PSEN2 for ontologies           About GeneDecksing



    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 
    OriGene Antibodies (see all 3): PSEN2
    OriGene Custom Antibody Services for PSEN2 
    GenScript Superior Antibodies for PSEN2
    Novus Biologicals PSEN2 Antibodies
    Abcam antibodies for PSEN2 
    Uscn Antibodies for PSEN2
    ThermoFisher Antibody for PSEN2

    Assay Products for PSEN2: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for PSEN2
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for PSEN2

    Protein Domains /
    Families
    for PSEN2 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    PSEN2 for domains           About GeneDecksing

    3 InterPro domains/families:
     IPR006639 Peptidase_A22
     IPR001108 Peptidase_A22A
     IPR001493 Pept_A22A_PS2

    Graphical View of Domain Structure for InterPro Entry P49810

    ProtoNet protein and cluster: P49810

    2 Blocks protein families:
    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


    Function
    for PSEN2 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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

         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

    miRNA
    Products:            		 OriGene 3'-UTR Clone (see all 2): PSEN2
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat PSEN2
    5 QIAGEN miScript miRNA 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 plasmid: PSEN2 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for PSEN2 (see all 7)
    OriGene shRNA RFP: PSEN2
    OriGene siRNA: PSEN2
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat PSEN2

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for PSEN2

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for PSEN2 (see all 5)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for PSEN2 (see all 3)
    OriGene custom cloning services – gene synthesis, subcloning, mutagenesis, variant library, vector shuttling 
    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 

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for PSEN2
    Search LifeMap BioReagents cell lines for PSEN2

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PSEN2

    Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004175endopeptidase activity IBA--
    GO:0004190aspartic-type endopeptidase activity IEA--
    GO:0005515protein binding IPI10748169


    PSEN2 for ontologies           About GeneDecksing


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

    Animal Models:
         Mouse knock-outs for PSEN2: Psen2tm1Haa Psen2tm1Bdes Psen2tm1Ber
         15/19 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  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  mortality/aging  nervous system 

    PSEN2 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for PSEN2 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/25 super-pathways (see all 25) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant
    8/11 pathways (see all 11)
    		Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant1.00
    		Signaling by NOTCH11.00
    		Signaling by NOTCH1 PEST Domain Mutants in Cancer1.00
    		Constitutive Signaling by NOTCH1 PEST Domain Mutants0.79
    		Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer1.00
    		Signaling by NOTCH0.77
    		Signaling by NOTCH1 in Cancer1.00
    		Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants0.71
    2NOTCH2 Activation and Transmission of Signal to the Nucleus
    		NOTCH2 Activation and Transmission of Signal to the Nucleus1.00
    		Activated NOTCH1 Transmits Signal to the Nucleus0.58
    		Signaling by NOTCH21.00
    3Notch Signaling Pathway
    		Notch Signaling Pathway1.00
    		Delta-Notch Signaling Pathway0.27
    		Notch signaling pathway0.82
    4Development_Notch Signaling Pathway
    		Development_Notch Signaling Pathway1.00
    		Development Notch Signaling Pathway0.97
    5Cell death signalling via NRAGE, NRIF and NADE
    		Cell death signalling via NRAGE, NRIF and NADE1.00
    		p75 NTR receptor-mediated signalling0.73

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 EMD Millipore Pathway for PSEN2
        Development Notch Signaling Pathway

    5 Downloadable PowerPoint Slides of QIAGEN 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

    5/25        Reactome Pathways for PSEN2 (see all 25)
        Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
    NRIF signals cell death from the nucleus
    A third proteolytic cleavage releases NICD
    FBXW7 Mutants and NOTCH1 in Cancer
    Cell death signalling via NRAGE, NRIF and NADE


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


    PSEN2 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for PSEN2

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

    5/88 Interacting proteins for PSEN2 (P498101, 2, 3 ENSP000003557474) via UniProtKB, MINT, STRING, and/or I2D (see all 88)
    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-4399546 I2D: score=1 
    ECSITQ9BQ951, 3EBI-2010251,EBI-712452 I2D: score=1 
    About this table

    Gene Ontology (GO): 5/43 biological process terms (GO ID links to tree view) (see all 43):    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 ----


    PSEN2 for ontologies           About GeneDecksing



    Drugs & Compounds
    for PSEN2 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    PSEN2 for compounds           About GeneDecksing

    EMD Millipore small molecules for PSEN2:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    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]
    Compound Wgamma-secretase inhibitor[173550-33-9]
    Begacestatgamma-secretase inhibitor; lowers Abeta40 and Abeta42 levels[769169-27-9]
    DAPTgamma-secretase inhibitor[208255-80-5]
    10/44 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about PSEN2 / PSN2 

    Transcripts
    for PSEN2 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat PSEN2
    5 QIAGEN miScript miRNA 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 plasmid: PSEN2 3' UTR sequence
    Inhib. RNA
    Products:             		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for PSEN2 (see all 7)
    OriGene shRNA RFP: PSEN2
    OriGene siRNA: PSEN2
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat PSEN2
    Clone
    Products:             		 OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for PSEN2 (see all 5)
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    OriGene custom cloning services – gene synthesis, subcloning, mutagenesis, variant library, vector shuttling 
    GenScript: all cDNA clones in your preferred vector (see all 2): PSEN2 (NM_000447)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PSEN2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PSEN2 
    Primer
    Products:            		 OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for PSEN2
    Browse OriGene validated miRNA SYBR primer pairs
    SABiosciences RT2 qPCR Primer Assay in human, mouse, rat PSEN2
      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat PSEN2
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat PSEN2

    Additional cDNA 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 

    24/173 AceView cDNA sequences (see all 173):

    AI927349 AI142959 AA993681 CD672922 AI340021 CA310542 AI474673 CD512951 
    AI675803 BX093003 CR594395 CK823284 CD358381 BI761633 CD513489 AL047795 
    AI924549 CD673541 AI093291 L43964 AI263363 CD673864 AU132195 AI347236 

    GeneLoc Exon Structure

    5/8 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

    Expression
    for PSEN2 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    PSEN2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: ATGTCCTTGT

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    PSEN2 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    4 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    CartilageCervical Intervertebral DiscIntervertebral Disc Nucleus Pulposus CellsCartilage
    CartilageLumbar Intervertebral DiscIntervertebral Disc Nucleus Pulposus CellsCartilage
    CartilageSacral Intervertebral DiscIntervertebral Disc Nucleus Pulposus CellsCartilage
    CartilageThoracic Intervertebral DiscIntervertebral Disc Nucleus Pulposus CellsCartilage
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See PSEN2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for PSEN2

    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

        SABiosciences Expression via Pathway-Focused 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

    Primer
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    In Situ
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    Orthologs
    for PSEN2 gene

    (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)
    About This Section
    This gene was present in the common ancestor of eukaryotes.

    Orthologs for PSEN2 gene from 8/27 species (see all 27)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves PSEN21 presenilin 2 (Alzheimer disease 4) 71.94(n)
    79.53(a)    		   374188  NM_204302.1  NP_989633.1 
    lizard
    (Anolis carolinensis)    		 Reptilia PSEN26
    		 --
    		 75(a)
    		 1 ↔ 1
    		 1(251060899-251076684)
    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 Psn6
    		 Presenilin
    		 43(a)
    		 1 → many
    		 3L(20425568-20428256)
    worm
    (Caenorhabditis elegans)    		 Secernentea sel-123 Expression: all stages 53(a)
    (best of 2)    		   X(951181-953466)   --
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons PS26
    PS16
    		 Presenilin-1
    		 29(a)
    25(a)
    		 many ↔ many
    many ↔ many
    		 2(12749746-12751125)
    1(2769815-2771477)
    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
    for PSEN2 gene

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

    PSEN2 for paralogs           About GeneDecksing



    Genomic Variants
    for PSEN2 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/747 NCBI SNPs in PSEN2 are shown (see all 747)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 1 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs637501101,2
    		Cpathogenic199391702(+) CATGGA/CCACCC 4 D A mis11Minor allele frequency- C:0.00EU 635
    rs637506661,2
    		Cpathogenic199391729(+) CTCCAC/TGGACA 4 T M mis11Minor allele frequency- T:0.00NA 4548
    rs637498841,2
    		Cpathogenic199398271(+) CTCATA/GGCCCT 4 I M mis10--------
    rs637502151,2
    		Cpathogenic199401647(+) GCTGAA/TCACCC 4 N I mis10--------
    rs637501971,2
    		C,F,pathogenic199401680(+) ACCCTC/TGGTGG 4 S L mis12Minor allele frequency- T:0.00NA EU 5857
    rs289363801,2
    		Cpathogenic199401704(+) CTACAC/GGCCAT 4 T R mis1 ese30--------
    rs637498511,2
    		Cpathogenic199401705(+) TCTACA/CCGCCA 4 T P mis10--------
    rs637500481,2
    		Cpathogenic199403434(+) CGGAGC/TGAAGC 4 A V mis10--------
    rs637502071,2
    		Cuntested199395477(+) GGAGCC/GTTCAT 4 P R mis11Minor allele frequency- G:0.00EU 1323
    rs637508801,2
    		Cuntested199398305(+) GCTGCA/TGCAGG 4 Q L mis10--------

    HapMap Linkage Disequilibrium report for PSEN2 (227057885 - 227083806 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for PSEN2: --
    Human Gene Mutation Database (HGMD): PSEN2

    Locus Specific Mutation Databases (LSDB): PSEN2

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing PSEN2
    DNA2.0 Custom Variant and Variant Library Synthesis for PSEN2

    Disorders / Diseases
    for PSEN2 gene

    (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.)
    About This Section
    PSEN2 for disorders           About GeneDecksing

    OMIM gene information: 600759   
    OMIM disorders: 606889  613697  
    UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810
  • Defects in PSEN2 are the cause of Alzheimer disease type 4 (AD4) [MIM:606889]. AD is an autosomal dominant
    • 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
  • Defects in PSEN2 are the cause of cardiomyopathy dilated type 1V (CMD1V) [MIM:613697]. It is a disorder
    • characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and
    arrhythmia. Patients are at risk of premature death

    20/52 diseases for PSEN2 (see all 52):    About MalaCards
    alzheimer's disease    basal ganglia calcification    familial idiopathic basal ganglia calcification    estrogen-receptor positive breast cancer
    early-onset familial alzheimer disease    age related macular degeneration    cerebral amyloid angiopathy    temporal lobe epilepsy
    frontotemporal dementia    macular degeneration    amyotrophic lateral sclerosis    prion disease
    alzheimer disease type 3    lateral sclerosis    bipolar disorder    ductal carcinoma in situ
    sporadic breast cancer    down syndrome    dilated cardiomyopathy    neurodegenerative disease

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

    10/35 Novoseek 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
    Early-Onset Familial Alzheimer Disease

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

    Export disorders for PSEN2 gene to outside databases

    Publications
    for PSEN2 gene

    (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)
    About This Section

    PubMed articles for PSEN2 gene, integrated from 9 sources (see all 583):
    (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. (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. (2002)
    3. 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. (1998)
    4. 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. (1996)
    5. 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. (2000)
    6. 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. (2006)
    7. 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. (2003)
    8. Presenilin mutations in Alzheimer's disease. (PubMed id 9521418)1, 2, 9 Cruts M. and van Broeckhoven C. (1998)
    9. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. (PubMed id 7651536)1, 2, 9 Rogaev E.I.... St George-Hyslop P.H. (1995)
    10. Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia. (PubMed id 15975068)1, 4, 9 Signorini S....Binetti G. (2004)

    External Searches for PSEN2 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing PSEN2 gene

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

    Other Databases showing PSEN2 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing PSEN2 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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/sites/GeneTests/lab/gene/PSEN2

    Intellectual Property
    for PSEN2 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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



    Products
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    About This Section

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