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    PSENEN presenilin enhancer 2 homolog (C. elegans) [ Homo sapiens (human) ]

    Gene ID: 55851, updated on 11-May-2013
    Official Symbol
    PSENENprovided by HGNC
    Official Full Name
    presenilin enhancer 2 homolog (C. elegans)provided by HGNC
    Primary source
    HGNC:30100
    Locus tag
    MDS033
    See related
    Ensembl:ENSG00000205155; HPRD:06362; MIM:607632; Vega:OTTHUMG00000182067
    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
    PEN2; PEN-2; MDS033; MSTP064
    Summary
    Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase. [provided by RefSeq, Jul 2008]
    Location :
    19q13.12
    Sequence :
    Chromosome: 19; NC_000019.9 (36236494..36237903)
    See PSENEN in Epigenomics, MapViewer

    Chromosome 19 - NC_000019.9Genomic Context describing neighboring genes Neighboring gene IGF-like family receptor 1 Neighboring gene U2 small nuclear RNA auxiliary factor 1-like 4 Neighboring gene lin-37 homolog (C. elegans) Neighboring gene heat shock protein, alpha-crystallin-related, B6

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    Products Interactant Other Gene Complex Source Pubs Description
    NP_758844.1 NP_057106.1 APH1A    BIND  PubMed PEN-2 interacts with APH-1. 
    NP_758844.1 NP_056146.1 NCSTN    BIND  PubMed PEN-2 interacts with NCT. 
    NP_758844.1 PSEN1    BIND  PubMed PEN-2 interacts with PS1. 
    Q9NZ42 Q96BI3 APH1A    HPRD  PubMed  
    Q9NZ42 Q92542 NCSTN    HPRD  PubMed  
    Q9NZ42 P49768 PSEN1    HPRD  PubMed  
    Q9NZ42 P49810 PSEN2    HPRD  PubMed  
    Q9NZ42 P49755 TMED10    HPRD  PubMed  
    BioGRID:120953 BioGRID:119296 APH1A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:120953 BioGRID:123659 APH1B    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:120953 BioGRID:116961 NCSTN    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:120953 BioGRID:111642 PSEN1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:120953 BioGRID:111643 PSEN2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:120953 BioGRID:112914 THBD    BioGRID  PubMed Two-hybrid 
    • 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...
    • 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...
    • Delta-Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Delta-Notch Signaling Pathway, organism-specific biosystemThere are 4 Notch receptors in humans (Notch 1-4) that bind to a family of 5 ligands (Jagged 1 and 2 and Delta-like 1-3). The Notch receptors are expressed on the cell surface as heterodimeric protei...
    • 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 ...
    • FBXW7 Mutants and NOTCH1 in Cancer, organism-specific biosystem (from REACTOME)
      FBXW7 Mutants and NOTCH1 in Cancer, organism-specific biosystemFBXW7 (FBW7) is a component of the SCF (SKP1, CUL1, and F-box protein) ubiquitin ligase complex SCF-FBW7 which is involved in the degradation of NOTCH1 (Oberg et al. 2001, Wu et al. 2001, Fryer et al...
    • 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...
    • 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, organism-specific biosystem (from Pathway Interaction Database)
      Notch signaling pathway, organism-specific biosystem
      Notch signaling pathway
    • 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...
    • Presenilin action in Notch and Wnt signaling, organism-specific biosystem (from Pathway Interaction Database)
      Presenilin action in Notch and Wnt signaling, organism-specific biosystem
      Presenilin action in Notch and Wnt signaling
    • 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 Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 HD Domain Mutants in Cancer, organism-specific biosystemNOTCH1 heterodimerization domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL) (Weng et al. 2004) and result in constitutive activity of NOTCH1 mutants (Malecki et al....
    • 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 NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant, organism-specific biosystem (from REACTOME)
      Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant, 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). The tran...
    • 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 a neighboring cell (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...
    • Syndecan-3-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      Syndecan-3-mediated signaling events, organism-specific biosystem
      Syndecan-3-mediated signaling events
    • 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 ...
    • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
      p75(NTR)-mediated signaling, organism-specific biosystem
      p75(NTR)-mediated signaling

    Markers

    Potential readthrough

    Included gene: LIN37

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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 
    apoptotic process TAS
    Traceable Author Statement
    more info
     
    apoptotic signaling pathway TAS
    Traceable Author Statement
    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
     
    neurotrophin TRK receptor signaling pathway 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 
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Golgi cisterna membrane IEA
    Inferred from Electronic Annotation
    more info
     
    endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
     
    integral to plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    gamma-secretase subunit PEN-2
    Names
    gamma-secretase subunit PEN-2
    hematopoietic stem/progenitor cells protein MDS033

    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_027934.1 RefSeqGene

      Range
      5001..6410
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_172341.1NP_758844.1  gamma-secretase subunit PEN-2

      Status: REVIEWED

      Source sequence(s)
      AF220053, BQ222622
      Consensus CDS
      CCDS12474.1
      UniProtKB/Swiss-Prot
      Q9NZ42
      Related
      ENSP00000222266, OTTHUMP00000268273, ENST00000222266, OTTHUMT00000459103
      Conserved Domains (1) summary
      pfam10251
      Location:699
      Blast Score: 379
      PEN-2; Presenilin enhancer-2 subunit of gamma secretase

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000019.9 Reference GRCh37.p10 Primary Assembly

      Range
      36236494..36237903
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000151.1 Alternate HuRef

      Range
      32741482..32742891
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018930.1 Alternate CHM1_1.0

      Range
      36395204..36396613
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

      Supplemental Content

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