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PSEN2 presenilin 2 [ Homo sapiens (human) ]

Gene ID: 5664, updated on 30-Oct-2014
Official Symbol
PSEN2provided by HGNC
Official Full Name
presenilin 2provided by HGNC
Primary source
HGNC:HGNC:9509
See related
Ensembl:ENSG00000143801; HPRD:02860; 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]
See PSEN2 in Epigenomics, MapViewer
Location:
1q42.13
Exon count:
13
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 1 NC_000001.11 (226870572..226896103)
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 ITPKB intronic transcript 1 (non-protein coding) Neighboring gene inositol-trisphosphate 3-kinase B Neighboring gene ribosomal protein S27 pseudogene 5 Neighboring gene aarF domain containing kinase 3 Neighboring gene CDC42 binding protein kinase alpha (DMPK-like) Neighboring gene cathepsin B pseudogene

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...
  • 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...
  • 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 ...
  • 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...
  • 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...
  • 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 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 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 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 IBA
Inferred from Biological aspect of Ancestor
more info
 
Notch receptor processing TAS
Traceable Author Statement
more info
PubMed 
Notch signaling pathway TAS
Traceable Author Statement
more info
 
T cell activation involved in immune response IEA
Inferred from Electronic Annotation
more info
 
T cell receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
amyloid precursor protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
amyloid precursor protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
 
beta-amyloid metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
brain morphogenesis IEA
Inferred from Electronic Annotation
more info
 
calcium ion transport IBA
Inferred from Biological aspect of Ancestor
more info
 
cardiac muscle contraction IEA
Inferred from Electronic Annotation
more info
 
cell fate specification IEA
Inferred from Electronic Annotation
more info
 
dorsal/ventral neural tube patterning IEA
Inferred from Electronic Annotation
more info
 
embryonic limb morphogenesis IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum calcium ion homeostasis IEA
Inferred from Electronic Annotation
more info
 
forebrain development IEA
Inferred from Electronic Annotation
more info
 
hair follicle development IEA
Inferred from Electronic Annotation
more info
 
hematopoietic progenitor cell differentiation IEA
Inferred from Electronic Annotation
more info
 
intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
 
locomotion IEA
Inferred from Electronic Annotation
more info
 
lung alveolus development 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
 
memory IEA
Inferred from Electronic Annotation
more info
 
myeloid leukocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
 
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein binding IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein complex assembly IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein phosphorylation IEA
Inferred from Electronic Annotation
more info
 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
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 
positive regulation of coagulation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors IEA
Inferred from Electronic Annotation
more info
 
protein processing IDA
Inferred from Direct Assay
more info
PubMed 
protein transport IEA
Inferred from Electronic Annotation
more info
 
regulation of epidermal growth factor-activated receptor activity IEA
Inferred from Electronic Annotation
more info
 
regulation of synaptic plasticity IEA
Inferred from Electronic Annotation
more info
 
response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
somitogenesis IEA
Inferred from Electronic Annotation
more info
 
thymus development IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
Z disc IBA
Inferred from Biological aspect of Ancestor
more info
 
apical plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
axon IBA
Inferred from Biological aspect of Ancestor
more info
 
cell cortex IBA
Inferred from Biological aspect of Ancestor
more info
 
cell surface IBA
Inferred from Biological aspect of Ancestor
more info
 
centrosome IDA
Inferred from Direct Assay
more info
PubMed 
ciliary basal body IEA
Inferred from Electronic Annotation
more info
 
ciliary rootlet IBA
Inferred from Biological aspect of Ancestor
more info
 
cytosol IEA
Inferred from Electronic Annotation
more info
 
dendritic shaft IBA
Inferred from Biological aspect of Ancestor
more info
 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
growth cone IBA
Inferred from Biological aspect of Ancestor
more info
 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
kinetochore IDA
Inferred from Direct Assay
more info
PubMed 
lysosomal membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
membrane raft IBA
Inferred from Biological aspect of Ancestor
more info
 
mitochondrial inner membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
neuromuscular junction IBA
Inferred from Biological aspect of Ancestor
more info
 
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
presenilin-2
AD5
E5-1
PS-2
AD3LP
STM-2
Alzheimer disease 4
NP_000438.2
NP_036618.2

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 

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

mRNA and Protein(s)

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

    See proteins identical to 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, OTTHUMP00000035671, ENST00000366783, OTTHUMT00000091539
    Conserved Domains (1) summary
    pfam01080
    Location:76439
    Presenilin; Presenilin
  2. NM_012486.2NP_036618.2  presenilin-2 isoform 2

    See proteins identical to 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, OTTHUMP00000228286, ENST00000422240, OTTHUMT00000091545
    Conserved Domains (1) summary
    pfam01080
    Location:76438
    Presenilin; Presenilin

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000001.11 

    Range
    226870572..226896103
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005273199.1XP_005273256.1  

    See proteins identical to XP_005273256.1

    UniProtKB/Swiss-Prot
    P49810
    Conserved Domains (1) summary
    pfam01080
    Location:76439
    Presenilin; Presenilin

Alternate HuRef

Genomic

  1. AC_000133.1 

    Range
    197575178..197600711
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 

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