PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''PYCARD''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
It is localized mainly in the
nucleus of
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s and
macrophage
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s. In case of pathogen infection, however, it relocalizes rapidly to the
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
, perinuclear space,
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
and
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
and it is a key adaptor protein in activation of the
inflammasome.
NMR structure of full-length ASC: PDB ID 2KN
ref>
Function
This gene encodes an adaptor protein that is composed of two protein–protein interaction domains: a
N-terminus, N-terminal PYRIN-PAAD-DAPIN domain (
PYD) and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
caspase-recruitment domain (
CARD
Card or The Card may refer to:
Common uses
* Plastic cards of various types:
**Bank card
**Credit card
**Debit card
**Payment card
* Playing card, used in games
* Printed circuit board, or card
* Greeting card, given on special occasions
Arts an ...
). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and
apoptotic signaling pathways via the activation of
caspase. In normal cells, this protein is localized to the
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery.
PYCARD can occur in four different
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
. Isoform 1, often referred to as canonical PYCARD, and isoform 2 are the activatory isoforms. They co-localize with
nucleotide oligomerization domain-like receptors (NLRs) and
caspase-1. Unlike isoform 1, isoform 2 is involved in direct
IL-1β processing regulation. Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to act as an adaptor protein in NLR signalling and its role remains elusive.
Interactions
PYCARD has been shown to
interact with
MEFV.
References
Further reading
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