Nicastrin
Encyclopedia
Nicastrin, also known as NCSTN, is a protein
which in humans is encoded by the NCSTN gene
.
Nicastrin (abbreviated NCT) is a protein
that is part of the gamma secretase
protein complex
, which is one of the protease
s involved in processing amyloid precursor protein
(APP) to the short Alzheimer's disease
-associated peptide amyloid beta
. The other proteins in the complex are presenilin
, which is the catalytically
active component of the complex, APH-1
(anterior pharynx-defective 1), and PEN-2
(presenilin enhancer 2). Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell. Nicastrin has also been identified as a regulator of neprilysin
, an enzyme
involved in the degradation of amyloid beta fragment.
, reflecting the fact that Alzheimer's disease was described in 1963 after studying descendants of an extended family originating in the village of Nicastro that had Familial Alzheimer's Disease (FAD).
with PSEN1
and PSEN2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the NCSTN gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Nicastrin (abbreviated NCT) is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that is part of the gamma secretase
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...
protein complex
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
, which is one of the protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s involved in processing amyloid precursor protein
Amyloid precursor protein
Amyloid precursor protein is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export...
(APP) to the short Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
-associated peptide amyloid beta
Amyloid beta
Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...
. The other proteins in the complex are presenilin
Presenilin
Presenilins are a family of related multi-pass transmembrane proteins that function as a part of the gamma-secretase intramembrane protease complex...
, which is the catalytically
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
active component of the complex, APH-1
APH-1
APH-1 is a protein gene product originally identified in the Notch signaling pathway in Caenorhabditis elegans as a regulator of the cell-surface localization of nicastrin...
(anterior pharynx-defective 1), and PEN-2
PEN-2
PEN-2 is a protein that is a regulatory component of the gamma secretase complex, a protease complex responsible for proteolysis of transmembrane proteins such as the Notch protein and amyloid precursor protein . The gamma secretase complex consists of PEN-2, APH-1, nicastrin, and the catalytic...
(presenilin enhancer 2). Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell. Nicastrin has also been identified as a regulator of neprilysin
Neprilysin
Neprilysin, also known as membrane metallo-endopeptidase, neutral endopeptidase , CD10, and common acute lymphoblastic leukemia antigen , is a zinc-dependent metalloprotease enzyme that degrades a number of small secreted peptides, most notably the amyloid beta peptide whose abnormal misfolding and...
, an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
involved in the degradation of amyloid beta fragment.
History
The protein was named after the Italian village NicastroNicastro
Nicastro was a small town in the province of Catanzaro, in the Calabria region of southern Italy.Since 1968 it constitutes, together with Sambiase and Sant'Eufemia Lamezia, the city of Lamezia Terme.- Geography :...
, reflecting the fact that Alzheimer's disease was described in 1963 after studying descendants of an extended family originating in the village of Nicastro that had Familial Alzheimer's Disease (FAD).
Interactions
Nicastrin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with PSEN1
PSEN1
Presenilin-1 is a protein that in humans is encoded by the PSEN1 gene.- Function :Alzheimer's disease patients with an inherited form of the disease carry mutations in the presenilin proteins or the amyloid precursor protein...
and PSEN2
PSEN2
Presenilin-2 is a protein that in humans is encoded by the PSEN2 gene.- Function :Alzheimer's disease patients with an inherited form of the disease carry mutations in the presenilin proteins or the amyloid precursor protein...
.