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Aliases for PSEN2 Gene

Aliases for PSEN2 Gene

  • Presenilin 2 2 3
  • STM2 3 4 6
  • AD4 3 4 6
  • Alzheimer Disease 4 2 3
  • CMD1V 3 6
  • AD3LP 3 4
  • STM-2 3 4
  • E5-1 3 4
  • PS-2 3 4
  • PS2 3 4
  • AD5 3 4
  • Presenilin-2 3
  • EC 3.4.23.- 4
  • EC 3.4.23 64
  • PSNL2 4
  • AD3L 3

External Ids for PSEN2 Gene

Previous Symbols for PSEN2 Gene

  • AD4

Summaries for PSEN2 Gene

Entrez Gene Summary for PSEN2 Gene

  • 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]

GeneCards Summary for PSEN2 Gene

PSEN2 (Presenilin 2) is a Protein Coding gene. Diseases associated with PSEN2 include early-onset autosomal dominant alzheimer disease and alzheimer disease-4. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include endopeptidase activity and aspartic-type endopeptidase activity. An important paralog of this gene is PSEN1.

UniProtKB/Swiss-Prot for PSEN2 Gene

  • 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.

Tocris Summary for PSEN2 Gene

  • 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 Alzheimers 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 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PSEN2 Gene

Genomics for PSEN2 Gene

Genomic Location for PSEN2 Gene

Start:
226,870,184 bp from pter
End:
226,896,103 bp from pter
Size:
25,920 bases
Orientation:
Plus strand

Genomic View for PSEN2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PSEN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PSEN2 Gene

Regulatory Elements for PSEN2 Gene

Proteins for PSEN2 Gene

  • Protein details for PSEN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49810-PSN2_HUMAN
    Recommended name:
    Presenilin-2
    Protein Accession:
    P49810
    Secondary Accessions:
    • A8K8D4
    • B1AP21
    • Q96P32

    Protein attributes for PSEN2 Gene

    Size:
    448 amino acids
    Molecular mass:
    50140 Da
    Quaternary structure:
    • 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.

    Alternative splice isoforms for PSEN2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PSEN2 Gene

Proteomics data for PSEN2 Gene at MOPED

Post-translational modifications for PSEN2 Gene

Other Protein References for PSEN2 Gene

Domains for PSEN2 Gene

UniProtKB/Swiss-Prot:

PSN2_HUMAN
Domain:
  • The PAL motif is required for normal active site conformation.:
    • P49810
Family:
  • Belongs to the peptidase A22A family.:
    • P49810
genes like me logo Genes that share domains with PSEN2: view

No data available for Gene Families for PSEN2 Gene

Function for PSEN2 Gene

Molecular function for PSEN2 Gene

GENATLAS Biochemistry: 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
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for PSEN2 Gene

Gene Ontology (GO) - Molecular Function for PSEN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IBA --
GO:0004190 aspartic-type endopeptidase activity IEA --
GO:0005515 protein binding IPI 10366599
genes like me logo Genes that share ontologies with PSEN2: view
genes like me logo Genes that share phenotypes with PSEN2: view

Animal Models for PSEN2 Gene

MGI Knock Outs for PSEN2:

No data available for miRNA , Transcription Factor Targeting and HOMER Transcription for PSEN2 Gene

Localization for PSEN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PSEN2 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PSEN2 Gene COMPARTMENTS Subcellular localization image for PSEN2 gene
Compartment Confidence
cytoskeleton 5
endoplasmic reticulum 5
golgi apparatus 5
nucleus 5
plasma membrane 4
lysosome 3
mitochondrion 3
vacuole 3
cytosol 2
extracellular 1

Gene Ontology (GO) - Cellular Components for PSEN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0000776 kinetochore IDA 9298903
GO:0005637 nuclear inner membrane IDA 9298903
GO:0005743 mitochondrial inner membrane IBA --
GO:0005765 lysosomal membrane IBA --
genes like me logo Genes that share ontologies with PSEN2: view

Pathways for PSEN2 Gene

genes like me logo Genes that share pathways with PSEN2: view

Gene Ontology (GO) - Biological Process for PSEN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0001708 cell fate specification IEA --
GO:0001756 somitogenesis IEA --
GO:0001933 negative regulation of protein phosphorylation IEA --
GO:0001942 hair follicle development IEA --
genes like me logo Genes that share ontologies with PSEN2: view

Compounds for PSEN2 Gene

(5) Tocris Compounds for PSEN2 Gene

Compound Action Cas Number
Begacestat gamma-secretase inhibitor; lowers Abeta40 and Abeta42 levels [769169-27-9]
DAPT gamma-secretase inhibitor [208255-80-5]
JLK 6 Inhibitor of gamma-secretase-mediated betaAPP processing [62252-26-0]
L-685,458 Potent and selective gamma-secretase inhibitor [292632-98-5]
MRK 560 gamma-secretase inhibitor; attenuates amyloid plaque deposition [677772-84-8]

(44) Novoseek inferred chemical compound relationships for PSEN2 Gene

Compound -log(P) Hits PubMed IDs
s-182 84.1 2
estrogen 70.8 97
ab-42 69.1 1
moxestrol 62.5 1
progesterone 61.2 56
genes like me logo Genes that share compounds with PSEN2: view

Transcripts for PSEN2 Gene

Unigene Clusters for PSEN2 Gene

Presenilin 2 (Alzheimer disease 4):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for PSEN2 Gene

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: -
SP6: - - -
SP7: - - -
SP8:

Relevant External Links for PSEN2 Gene

GeneLoc Exon Structure for
PSEN2
ECgene alternative splicing isoforms for
PSEN2

Expression for PSEN2 Gene

mRNA expression in normal human tissues for PSEN2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for PSEN2 Gene

SOURCE GeneReport for Unigene cluster for PSEN2 Gene Hs.25363

mRNA Expression by UniProt/SwissProt for PSEN2 Gene

P49810-PSN2_HUMAN
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.
genes like me logo Genes that share expressions with PSEN2: view

Orthologs for PSEN2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PSEN2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PSEN2 36
  • 99.33 (n)
  • 99.78 (a)
PSEN2 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PSEN2 36
  • 91.82 (n)
  • 96.87 (a)
PSEN2 37
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PSEN2 36
  • 90.62 (n)
  • 95.98 (a)
PSEN2 37
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Psen2 36
  • 89.58 (n)
  • 95.98 (a)
Psen2 16
Psen2 37
  • 96 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PSEN2 37
  • 79 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PSEN2 37
  • 74 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Psen2 36
  • 89.51 (n)
  • 95.31 (a)
chicken
(Gallus gallus)
Aves PSEN2 36
  • 72.02 (n)
  • 79.53 (a)
PSEN2 37
  • 77 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PSEN2 37
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia psen2 36
  • 67.73 (n)
  • 75.74 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 36
psen2 36
  • 69.37 (n)
  • 74.01 (a)
psen2 37
  • 70 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002957 36
  • 62.4 (n)
  • 63.79 (a)
fruit fly
(Drosophila melanogaster)
Insecta Psn 36
  • 58.58 (n)
  • 57.21 (a)
Psn 37
  • 44 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea hop-1 37
  • 32 (a)
ManyToMany
sel-12 37
  • 48 (a)
ManyToMany
spe-4 37
  • 18 (a)
ManyToMany
sel-12 38
  • 53 (a)
hop-1 38
  • 31 (a)
rice
(Oryza sativa)
Liliopsida Os.11448 36
Os01g0276400 36
  • 55.21 (n)
  • 48.02 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.1400 37
  • 61 (a)
OneToMany
Species with no ortholog for PSEN2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PSEN2 Gene

ENSEMBL:
Gene Tree for PSEN2 (if available)
TreeFam:
Gene Tree for PSEN2 (if available)

Paralogs for PSEN2 Gene

Paralogs for PSEN2 Gene

Selected SIMAP similar genes for PSEN2 Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with PSEN2: view

Variants for PSEN2 Gene

Sequence variations from dbSNP and Humsavar for PSEN2 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs6759 -- 226,882,036(+) GAGAA(C/T)ACTGC reference, synonymous-codon
rs7961 -- 226,875,528(+) GACCT(C/T)TCTGC utr-variant-5-prime
rs11405 -- 226,881,976(+) TCGGC(C/T)GAGAG synonymous-codon, reference
rs732479 -- 226,877,777(+) AGGCC(A/G)CATGT intron-variant
rs743601 -- 226,892,465(+) CCTAA(C/T)ACCCA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PSEN2 Gene

Variant ID Type Subtype PubMed ID
nsv4766 CNV Loss 18451855

Relevant External Links for PSEN2 Gene

HapMap Linkage Disequilibrium report
PSEN2
Human Gene Mutation Database (HGMD)
PSEN2
Locus Specific Mutation Databases (LSDB)
PSEN2

Disorders for PSEN2 Gene

(2) OMIM Diseases for PSEN2 Gene (600759)

UniProtKB/Swiss-Prot

PSN2_HUMAN
  • Alzheimer disease 4 (AD4) [MIM:606889]: A familial early-onset form of 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. {ECO:0000269 PubMed:10631141, ECO:0000269 PubMed:10732806, ECO:0000269 PubMed:22503161, ECO:0000269 PubMed:7638622, ECO:0000269 PubMed:7651536, ECO:0000269 PubMed:9384602}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cardiomyopathy, dilated 1V (CMD1V) [MIM:613697]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269 PubMed:17186461}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for PSEN2 Gene

(35) Novoseek inferred disease relationships for PSEN2 Gene

Disease -log(P) Hits PubMed IDs
alzheimers disease 89.2 134
early onset alzheimer disease 84.9 6
senile plaques 75.1 11
neurofibrillary tangles 67.4 6
dementia 63 13

Relevant External Links for PSEN2

GeneTests
PSEN2
GeneReviews
PSEN2
Genetic Association Database (GAD)
PSEN2
Human Genome Epidemiology (HuGE) Navigator
PSEN2
genes like me logo Genes that share disorders with PSEN2: view

Publications for PSEN2 Gene

  1. Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene. (PMID: 8661049) Levy-Lahad E. … Schellenberg G.D. (Genomics 1996) 3 4 23
  2. Interaction of presenilins with the filamin family of actin-binding proteins. (PMID: 9437013) Zhang W. … Wu J.Y. (J. Neurosci. 1998) 3 4 23
  3. High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. (PMID: 10631141) Finckh U. … Gal A. (Am. J. Hum. Genet. 2000) 3 4 23
  4. The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation. (PMID: 10652302) Kimberly W.T. … Selkoe D.J. (J. Biol. Chem. 2000) 3 4 23
  5. A novel mutation in the predicted TM2 domain of the presenilin 2 gene in Spanish patient with late-onset Alzheimer's disease. (PMID: 10732806) Lao J.I. … Cacabelos R. (Neurogenetics 1998) 3 4 23

Products for PSEN2 Gene

Sources for PSEN2 Gene

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