Beta-secretase 2 (, also known as Memapsin-1) is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
that cleaves Glu-Val-Asn-Leu!Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's
amyloid precursor protein
Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator ...
. BACE2 is a close
homolog
In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the Bat wing development, wings of bats and Ori ...
of
BACE1.
Function
Cerebral deposition of amyloid beta peptide is an early and critical feature of
Alzheimer's disease and a frequent complication of
Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with child development, physical growth delays, mild to moderate ...
.
Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein by 2 proteases, one of which is the protein encoded by this gene. This gene localizes to the 'Down critical region' of chromosome 21. The encoded protein, a member of the peptidase A1 protein family, is a type I integral membrane glycoprotein and
aspartic protease
Aspartic proteases are a catalytic type of protease enzymes that use an activated water molecule bound to one or more aspartate residues for catalysis of their peptide substrates. In general, they have two highly conserved aspartates in the ac ...
. Three transcript variants encoding different isoforms have been described for this gene.
It has been reported that BACE2 is the main protease that mediates the release of the amyloidogenic ectodomain of
Pmel17
Melanocyte protein PMEL also known as premelanosome protein (PMEL) or silver locus protein homolog (SILV) is a protein that in humans is encoded by the ''PMEL'' gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
St ...
in melanocytes.
BACE2 has also been observed in mice to be correlated with maintaining the
pancreatic β cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dim ...
s and improving control of glucose homeostasis, which may prove to be useful for research on
Type 2 Diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinati ...
.
Interactions
BACE2 has been shown to
interact with
GGA1
ADP-ribosylation factor-binding protein GGA1 is a protein that in humans is encoded by the ''GGA1'' gene.
This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) protein family. Members of this family ar ...
and
GGA2.
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References
Further reading
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External links
* https://web.archive.org/web/20070318110931/http://www.ihop-net.org/UniPub/iHOP/gs/129262.html
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EC 3.4.23
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