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    PSEN2 presenilin 2 [ Homo sapiens (human) ]

    Gene ID: 5664, updated on 7-May-2017
    Official Symbol
    PSEN2provided by HGNC
    Official Full Name
    presenilin 2provided by HGNC
    Primary source
    HGNC:HGNC:9509
    See related
    Ensembl:ENSG00000143801 MIM:600759; Vega:OTTHUMG00000037563
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AD4; PS2; AD3L; STM2; CMD1V
    Summary
    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]
    Orthologs
    Location:
    1q42.13
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 1 NC_000001.11 (226870572..226903829)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (227057885..227083804)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein S27 pseudogene 5 Neighboring gene uncharacterized LOC105373119 Neighboring gene uncharacterized LOC107985354 Neighboring gene coenzyme Q8A Neighboring gene glucose-dependent insulinotropic receptor-like

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Replication interactions

    Interaction Pubs
    Knockdown of presenilin 2 (Alzheimer disease 4, PSEN2) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Go to the HIV-1, Human Interaction Database

    • Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystem (from REACTOME)
      Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystemMature NOTCH1 heterodimer on the cell surface is activated by one of its ligands: DLL1 (Cordle et al. 2008, Jarriault et al. 1998), DLL4 (Benedito et al. 2009), JAG1 (Li et al. 1998, Benedito et al. ...
    • Alzheimer's disease, organism-specific biosystem (from KEGG)
      Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimer's disease, conserved biosystem (from KEGG)
      Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
      Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
    • Axon guidance, organism-specific biosystem (from REACTOME)
      Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
    • Canonical and Non-canonical Notch signaling, organism-specific biosystem (from WikiPathways)
      Canonical and Non-canonical Notch signaling, organism-specific biosystemThis pathway is based on figure 1 of "Alteration of Notch signaling in skeletal development and disease" (see bibliography). In the NOTCH signaling pathway, mammals have 11 ligands (JAG, DLL, DLK, et...
    • Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystem (from REACTOME)
      Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystemp75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNG...
    • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystem (from REACTOME)
      Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystemWhen found in cis, HD and PEST domain mutations act synergistically, increasing NOTCH1 transcriptional activity up to ~40-fold, compared with up to ~10-fold and up to ~2-fold increase with HD mutatio...
    • Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystem (from REACTOME)
      Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystemAs NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signal...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
      Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
    • EPH-Ephrin signaling, organism-specific biosystem (from REACTOME)
      EPH-Ephrin signaling, organism-specific biosystemDuring the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct dest...
    • EPH-ephrin mediated repulsion of cells, organism-specific biosystem (from REACTOME)
      EPH-ephrin mediated repulsion of cells, organism-specific biosystemDespite high-affinity multimeric interaction between EPHs and ephrins (EFNs), the cellular response to EPH-EFN engagement is usually repulsion between the two cells and signal termination. These repu...
    • LKB1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      LKB1 signaling events, organism-specific biosystem
      LKB1 signaling events
    • NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystem (from REACTOME)
      NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystemSimilar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004...
    • NRIF signals cell death from the nucleus, organism-specific biosystem (from REACTOME)
      NRIF signals cell death from the nucleus, organism-specific biosystemNRIF (nuclear receptor-interacting factor) is a DNA binding protein that is essential for p75-mediated apoptosis in retina and sympathetic neurons. Neurotrophin or proneurotrophin binding to p75TR in...
    • Neurotrophin signaling pathway, organism-specific biosystem (from KEGG)
      Neurotrophin signaling pathway, organism-specific biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Neurotrophin signaling pathway, conserved biosystem (from KEGG)
      Neurotrophin signaling pathway, conserved biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Notch Signaling Pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
    • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Notch Signaling Pathway, organism-specific biosystemThe Notch pathway is an evolutionally conserved signaling pathway which plays an important role in diverse developmental and physiological processes. These include cell-fate determination, tissue pat...
    • Notch signaling, organism-specific biosystem (from KEGG)
      Notch signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
    • Notch signaling, conserved biosystem (from KEGG)
      Notch signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
    • Notch signaling pathway, organism-specific biosystem (from KEGG)
      Notch signaling pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
    • Notch signaling pathway, conserved biosystem (from KEGG)
      Notch signaling pathway, conserved biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
    • Nuclear signaling by ERBB4, organism-specific biosystem (from REACTOME)
      Nuclear signaling by ERBB4, organism-specific biosystemBesides signaling as a transmembrane receptor, ligand activated homodimers of ERBB4 JM-A isoforms (ERBB4 JM-A CYT1 and ERBB4 JM-A CYT2) undergo proteolytic cleavage by ADAM17 (TACE) in the juxtamembr...
    • Regulated proteolysis of p75NTR, organism-specific biosystem (from REACTOME)
      Regulated proteolysis of p75NTR, organism-specific biosystemp75NTR undergoes a process of regulated intramembrane proteolysis (RIP) similar to other transmembrane proteins such as NOTCH, beta-amyloid precursor protein (APP), and ERBB4. Each of these proteins ...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
      Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
    • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
    • Signaling by NOTCH1, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1, organism-specific biosystemNOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.NOTCH1 receptor presented on the plasma membrane is activated by a me...
    • Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystemMutations in the heterodimerization domain (HD) and PEST domain of NOTCH1 are frequently found in cis in T-cell acute lymphoblastic leukemia. While HD mutations alone result in up to ~10-fold increas...
    • Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystemNOTCH1 PEST domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL). PEST domain mutations interfere with ubiquitination-mediated NOTCH1 downregulation and result in prol...
    • Signaling by NOTCH1 in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 in Cancer, organism-specific biosystemHuman NOTCH1 was cloned as a chromosome 9 gene, translocated to the T-cell beta receptor (TCBR) promoter on chromosome 7 in T-cell acute lymphoblastic leukemia (T-ALL) (Ellisen et al. 1991). This tra...
    • Signaling by NOTCH2, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH2, organism-specific biosystemNOTCH2 is activated by binding Delta-like and Jagged ligands (DLL/JAG) expressed in trans on neighboring cells (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). In trans ...
    • Signaling by NOTCH3, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH3, organism-specific biosystemSimilar to NOTCH1, NOTCH3 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH3, first by ADAM10 at the S2 cleav...
    • Signaling by NOTCH4, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH4, organism-specific biosystemSimilar to NOTCH1, NOTCH4 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH4, first by ADAM10 at the S2 cleav...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
      p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    aspartic-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
     
    endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    Notch receptor processing TAS
    Traceable Author Statement
    more info
    PubMed 
    Notch signaling pathway TAS
    Traceable Author Statement
    more info
     
    amyloid precursor protein catabolic process TAS
    Traceable Author Statement
    more info
    PubMed 
    beta-amyloid metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    calcium ion transport IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    ephrin receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    membrane protein ectodomain proteolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane protein intracellular domain proteolysis TAS
    Traceable Author Statement
    more info
     
    negative regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of apoptotic process TAS
    Traceable Author Statement
    more info
     
    positive regulation of catalytic activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein processing IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
     
    Z disc IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    centrosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
     
    integral component of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    kinetochore IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    neuronal cell body IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    nuclear inner membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    perinuclear region of cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    presenilin-2
    Names
    AD3LP
    AD5
    Alzheimer disease 4
    E5-1
    PS-2
    STM-2
    NP_000438.2
    NP_036618.2
    XP_005273256.1
    XP_016857324.1
    XP_016857325.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007381.1 RefSeqGene

      Range
      5001..30532
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000447.2NP_000438.2  presenilin-2 isoform 1

      See identical proteins and their annotated locations for NP_000438.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AI091221, BT006984, DA198818, DA915823, L43964
      Consensus CDS
      CCDS1556.1
      UniProtKB/Swiss-Prot
      P49810
      Related
      ENSP00000355747.3, OTTHUMP00000035671, ENST00000366783.7, OTTHUMT00000091539
      Conserved Domains (1) summary
      pfam01080
      Location:82438
      Presenilin; Presenilin
    2. NM_012486.2NP_036618.2  presenilin-2 isoform 2

      See identical proteins and their annotated locations for NP_036618.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice acceptor site at exon 10 compared to transcript variant 1, resulting in an isoform (2) that is 1 aa shorter than isoform 1.
      Source sequence(s)
      AI091221, DA198818, DA915823, L43964, U34349
      Consensus CDS
      CCDS44324.1
      UniProtKB/Swiss-Prot
      P49810
      Related
      ENSP00000403737.2, OTTHUMP00000228286, ENST00000422240.6, OTTHUMT00000091545
      Conserved Domains (1) summary
      pfam01080
      Location:82437
      Presenilin; Presenilin

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p7 Primary Assembly

      Range
      226870572..226903829
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017001836.1XP_016857325.1  presenilin-2 isoform X2

      UniProtKB/Swiss-Prot
      P49810
      Related
      ENSP00000486498.1, ENST00000626989.2
      Conserved Domains (1) summary
      pfam01080
      Location:82437
      Presenilin; Presenilin
    2. XM_005273199.3XP_005273256.1  presenilin-2 isoform X1

      See identical proteins and their annotated locations for XP_005273256.1

      UniProtKB/Swiss-Prot
      P49810
      Conserved Domains (1) summary
      pfam01080
      Location:82438
      Presenilin; Presenilin
    3. XM_017001835.1XP_016857324.1  presenilin-2 isoform X1

      UniProtKB/Swiss-Prot
      P49810
      Conserved Domains (1) summary
      pfam01080
      Location:82438
      Presenilin; Presenilin

    RNA

    1. XR_001737316.1 RNA Sequence

    2. XR_001737317.1 RNA Sequence

    3. XR_001737318.1 RNA Sequence

    4. XR_949149.1 RNA Sequence

    5. XR_949150.2 RNA Sequence

    6. XR_001737321.1 RNA Sequence

    7. XR_001737319.1 RNA Sequence

    8. XR_001737320.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018912.2 Alternate CHM1_1.1

      Range
      228331030..228356564
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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