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 (AD) patients with an inherited form of the disease carry mutations in the
presenilin proteins (
PSEN1; 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 format ...
(APP). These disease-linked mutations result in increased production of the longer form of
amyloid-beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
(main component of
amyloid
Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the huma ...
deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on
gamma-secretase
Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. Th ...
, 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 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 factor ...
.
Interactions
PSEN2 has been shown to
interact
Advocates for Informed Choice, 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 traits. The organizati ...
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,
and
*
UBQLN1.
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