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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
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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 Variation Viewer (GRCh37.p13)

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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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

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