Caspase-6 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 in humans is encoded by the ''CASP6''
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 ...
.
''CASP6''
orthologs
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...
have been identified in numerous
mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fu ...
for which complete genome data are available. Unique orthologs are also present in
birds
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...
,
lizards
Lizards are a widespread group of squamate reptiles, with over 7,000 species, ranging across all continents except Antarctica, as well as most oceanic island chains. The group is paraphyletic since it excludes the snakes and Amphisbaenia a ...
,
lissamphibian
The Lissamphibia is a group of tetrapods that includes all modern amphibians. Lissamphibians consist of three living groups: the Salientia (frogs, toads, and their extinct relatives), the Caudata (salamanders, newts, and their extinct relative ...
s, and
teleosts
Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Teleo ...
. Caspase-6 has known functions in
apoptosis,
early
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
and
neurodegeneration
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
in
Huntington's
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
and
Alzheimer's disease.
Function
This gene encodes a protein that is a member of the
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, s ...
-
aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α- amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pr ...
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 form ...
(
caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyst ...
) family. Sequential activation of caspases plays a central role in the execution-phase of cell
apoptosis.
Caspases exist as inactive
proenzyme
In biochemistry, a zymogen (), also called a proenzyme (), is an inactive precursor of an enzyme. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the acti ...
s that undergo
proteolytic
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases ...
processing at conserved aspartic residues to produce two subunits, large and small, that
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ( ...
ize to form the active enzyme. This protein is processed by
caspases 7,
8 and
10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family.
Alternative splicing of this gene results in two transcript variants that encode different isoforms.
Caspase-6 plays a role in the early immune response via de-repression. It reduces the expression of the immunosuppressant cytokine
interleukin-10
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 ...
and cleaves the macrophage suppressing
IRAK-M.
With respect to
neurodegeneration
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
, caspase-6 cleaves
HTT in
Huntington's
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
and
APP
App, Apps or APP may refer to:
Computing
* Application software
* Mobile app, software designed to run on smartphones and other mobile devices
* Web application or web app, software designed to run inside a web browser
* Adjusted Peak Performan ...
in
Alzheimer's disease. Resulting in both cases in
protein aggregation
In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly. Protein aggregates have been implicated in a wi ...
of the fragments.
Interactions
Caspase 6 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 organizat ...
with
Caspase 8
Caspase-8 is a caspase protein, encoded by the ''CASP8'' gene. It most likely acts upon caspase-3.
''CASP8'' orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also prese ...
.
See also
*
The Proteolysis Map
The Proteolysis MAP (PMAP) is an integrated web resource focused on proteases.
Rationale
PMAP is to aid the protease researchers in reasoning about proteolytic networks and metabolic pathways.
History and funding
PMAP was originally create ...
*
Caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyst ...
References
Further reading
*
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*
*
*
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*
*
*
External links
* The
MEROPS
MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibi ...
online database for peptidases and their inhibitors
C14.005*
{{Portal bar, Biology, border=no
EC 3.4.22
Caspases