Presenilin-2 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that (in humans) is encoded by the ''PSEN2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As ...
(AD) patients with an inherited form of the disease carry mutations in the
presenilin
Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onse ...
proteins (
PSEN1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the ''PSEN1'' gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta ...
; PSEN2) or the
amyloid precursor protein
Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse forma ...
(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 __NOTOC__
__FORCETOC__
Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in metazoans. The Notch extracellular domain mediates interactions with DSL ...
, such that they either directly regulate gamma-secretase activity or themselves are
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
enzymes. Two alternative transcripts of PSEN2 have been identified.
In melanocytic cells PSEN2 gene expression may be regulated by
MITF
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene.
MITF is a basic helix-loop-helix leucine zipper transcription fact ...
.
Interactions
PSEN2 has been shown to
interact
Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...
with:
*
BCL2-like 1,
*
CAPN1
Calpain-1 catalytic subunit (CANP 1) is a protein that in humans is encoded by the ''CAPN1'' gene.
Function
The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ...
,
*
CIB1
Calcium and integrin-binding protein 1 is a protein that in humans is encoded by the ''CIB1'' gene.
The protein encoded by this gene is a member of the calcium-binding protein family. The specific function of this protein has not yet been determ ...
,
*
Calsenilin
Calsenilin is a protein that in humans is encoded by the ''KCNIP3'' gene.
Function
This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the neuronal calcium sensor family of p ...
,
*
FHL2
Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the ''FHL2'' gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.
Function
FHL-2 is thought to have ...
,
*
FLNB
Filamin B, beta (FLNB), also known as Filamin B, beta (truncated actin binding protein 278 homolog), is a cytoplasmic protein which in humans is encoded by the ''FLNB'' gene.
FLNB regulates intracellular communication and signalling by cross-linki ...
,
*
KCNIP4
Kv channel-interacting protein 4 is a protein that in humans is encoded by the ''KCNIP4'' gene.
This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch o ...
,
*
Nicastrin
Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the ''NCSTN'' gene.
Function
Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in process ...
,
and
*
UBQLN1
Ubiquilin-1 is a protein that in humans is encoded by the ''UBQLN1'' gene.
Ubiquilins contain two domains, an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and u ...
.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease
{{gene-1-stub
Alzheimer's disease