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    PSEN2 presenilin 2 [ Homo sapiens (human) ]

    Gene ID: 5664, updated on 3-Nov-2024

    Summary

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    Official Symbol
    PSEN2provided by HGNC
    Official Full Name
    presenilin 2provided by HGNC
    Primary source
    HGNC:HGNC:9509
    See related
    Ensembl:ENSG00000143801 MIM:600759; AllianceGenome:HGNC:9509
    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]
    Expression
    Ubiquitous expression in testis (RPKM 4.6), prostate (RPKM 4.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PSEN2 in Genome Data Viewer
    Location:
    1q42.13
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (226870616..226903668)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (226058503..226091743)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (227058317..227083799)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904530 Neighboring gene Sharpr-MPRA regulatory region 12356 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:227038591-227039325 Neighboring gene uncharacterized LOC105373119 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:227051075-227051623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1893 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1894 Neighboring gene MPRA-validated peak736 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2673 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:227083595-227083826 Neighboring gene uncharacterized LOC107985354 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:227126665-227127356 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1895 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1896 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:227138969-227139468 Neighboring gene coenzyme Q8A Neighboring gene MPRA-validated peak738 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:227161529-227162142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:227166346-227167094 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:227172247-227172425

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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 Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Presenilin-2 polymorphisms and risk of sporadic AD: evidence from a meta-analysis. Chen C, et al. Gene, 2012 Jul 25. PMID 22580083
    2. PEN-2 overexpression induces gamma-secretase protein and its activity with amyloid beta-42 production. Seo SJ, et al. Neurochem Res, 2007 Jun. PMID 17401676
    3. A novel PSEN2 mutation associated with a peculiar phenotype. Piscopo P, et al. Neurology, 2008 Apr 22. PMID 18427071
    4. Three-year follow-up of a patient with early-onset Alzheimer's disease with presenilin-2 N141I mutation - case report and review of the literature. Nikisch G, et al. Eur J Med Res, 2008 Dec 3. PMID 19073399
    5. A novel Italian presenilin 2 gene mutation with prevalent behavioral phenotype. Marcon G, et al. J Alzheimers Dis, 2009. PMID 19276543

    See all (255) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Presenilin deficiency enhances tau phosphorylation and its secretion.
      Title: Presenilin deficiency enhances tau phosphorylation and its secretion.
    2. Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications.
      Title: Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications.
    3. Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development.
      Title: Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development.
    4. Quantitative comparison of presenilin protein expression reveals greater activity of PS2-gamma-secretase.
      Title: Quantitative comparison of presenilin protein expression reveals greater activity of PS2-γ-secretase.
    5. Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the gamma-secretase subunit presenilin.
      Title: Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the γ-secretase subunit presenilin.
    6. Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer's disease.
      Title: Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer's disease.
    7. The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.
      Title: The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.
    8. PSEN2 Mutation Spectrum and Novel Functionally Validated Mutations in Alzheimer's Disease: Data from PUMCH Dementia Cohort.
      Title: PSEN2 Mutation Spectrum and Novel Functionally Validated Mutations in Alzheimer's Disease: Data from PUMCH Dementia Cohort.
    9. Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.
      Title: Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.
    10. A Rare Variation in the 3' Untranslated Region of the Presenilin 2 Gene Is Linked to Alzheimer's Disease.
      Title: A Rare Variation in the 3' Untranslated Region of the Presenilin 2 Gene Is Linked to Alzheimer's Disease.
    Submit: New GeneRIF Correction See all GeneRIFs (160)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables aspartic endopeptidase activity, intramembrane cleaving IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Notch receptor processing TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in Notch signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in amyloid precursor protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in amyloid precursor protein catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in amyloid-beta formation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in amyloid-beta formation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in membrane protein ectodomain proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in membrane protein ectodomain proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrion-endoplasmic reticulum membrane tethering IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of calcium import into the mitochondrion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in centrosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in early endosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of gamma-secretase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of gamma-secretase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in kinetochore IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in nuclear inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in synaptic vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    presenilin-2
    Names
    AD3LP
    AD5
    Alzheimer disease 3-like
    Alzheimer disease 4
    E5-1
    PS-2
    STM-2
    NP_000438.2
    NP_036618.2
    XP_005273256.1
    XP_016857324.1
    XP_016857325.1
    XP_047281552.1
    XP_047281553.1
    XP_047281557.1
    XP_054193713.1
    XP_054193714.1
    XP_054193715.1
    XP_054193716.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_007381.2 RefSeqGene

      Range
      5433..30915
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_225

    mRNA and Protein(s)

    1. NM_000447.3 → NP_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)
      BT006984, DA198818, DA915823, L43964
      Consensus CDS
      CCDS1556.1
      UniProtKB/Swiss-Prot
      A8K8D4, B1AP21, P49810, Q96P32
      UniProtKB/TrEMBL
      A0A218KGQ4
      Related
      ENSP00000355747.3, ENST00000366783.8
      Conserved Domains (1) summary
      pfam01080
      Location:82 → 438
      Presenilin

    2. NM_012486.3 → NP_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)
      DA198818, DA915823, L43964, U34349
      Consensus CDS
      CCDS44324.1
      UniProtKB/TrEMBL
      A0A218KGQ4
      Related
      ENSP00000403737.2, ENST00000422240.6
      Conserved Domains (1) summary
      pfam01080
      Location:82 → 437
      Presenilin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      226870616..226903668
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047425601.1 → XP_047281557.1  presenilin-2 isoform X2

    2. XM_017001835.2 → XP_016857324.1  presenilin-2 isoform X1

      UniProtKB/Swiss-Prot
      A8K8D4, B1AP21, P49810, Q96P32
      UniProtKB/TrEMBL
      A0A218KGQ4
      Conserved Domains (1) summary
      pfam01080
      Location:82 → 438
      Presenilin

    3. XM_047425596.1 → XP_047281552.1  presenilin-2 isoform X1

      UniProtKB/Swiss-Prot
      A8K8D4, B1AP21, P49810, Q96P32
      Related
      ENSP00000504727.1, ENST00000679088.1

    4. XM_047425597.1 → XP_047281553.1  presenilin-2 isoform X2

    5. XM_005273199.5 → XP_005273256.1  presenilin-2 isoform X1

      See identical proteins and their annotated locations for XP_005273256.1

      UniProtKB/Swiss-Prot
      A8K8D4, B1AP21, P49810, Q96P32
      UniProtKB/TrEMBL
      A0A218KGQ4
      Related
      ENSP00000503116.1, ENST00000677414.1
      Conserved Domains (1) summary
      pfam01080
      Location:82 → 438
      Presenilin

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

      UniProtKB/TrEMBL
      A0A218KGQ4
      Related
      ENSP00000503244.1, ENST00000676747.1
      Conserved Domains (1) summary
      pfam01080
      Location:82 → 437
      Presenilin

    RNA

    1. XR_001737316.3 RNA Sequence

    2. XR_007061979.1 RNA Sequence

    3. XR_007061980.1 RNA Sequence

    4. XR_949150.4 RNA Sequence

      Related
      ENST00000676840.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      226058503..226091743
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054337739.1 → XP_054193714.1  presenilin-2 isoform X1

      UniProtKB/Swiss-Prot
      A8K8D4, B1AP21, P49810, Q96P32

    2. XM_054337740.1 → XP_054193715.1  presenilin-2 isoform X2

    3. XM_054337738.1 → XP_054193713.1  presenilin-2 isoform X1

      UniProtKB/Swiss-Prot
      A8K8D4, B1AP21, P49810, Q96P32

    4. XM_054337741.1 → XP_054193716.1  presenilin-2 isoform X2

    RNA

    1. XR_008486112.1 RNA Sequence

    2. XR_008486110.1 RNA Sequence

    3. XR_008486111.1 RNA Sequence

    4. XR_008486113.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49810.1 GenPept UniProtKB/Swiss-Prot:P49810

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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