CARD (domain)
| Caspase recruitment domain | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CDD | cd01671 | ||||||||||
| |||||||||||
| Caspase recruitment domain, IPS1/RIG-I | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | CARD_2 | ||||||||
SCOP2 | 2lwd / SCOPe / SUPFAM | ||||||||
| CDD | cd08789 | ||||||||
| |||||||||
Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs. CARDs are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors.
Basic features
CARDs are a subclass of protein motif known as the death fold, which features an arrangement of six to seven antiparallel alpha helices with a hydrophobic core and an outer face composed of charged residues. Other motifs in this class include the pyrin domain (PYD), death domain (DD), and death effector domain (DED), all of which also function primarily in regulation of apoptosis and inflammatory responses.
In apoptosis
CARDs were originally characterized based on their involvement in the regulation of caspase activation and apoptosis.[2] The basic six-helix structure of the domain appears to be conserved as far back as the ced-3 and ced-4 genes in C. elegans, the organism in which several components of the apoptotic machinery were first characterized. CARDs are present on a number of proteins that promote apoptosis, primarily caspases 1,2,4,5,9, and 15 in mammals.
In the mammalian immune response
IL-1 and IL-18 processing
A number of CARDs have been shown to play a role in regulating inflammation in response to bacterial and viral pathogens as well as to a variety of endogenous stress signals. Recently, studies on the NLR protein Ipaf-1 have provided insight into how CARDs participate in the immune response. Ipaf-1 features an N-terminal CARD, a nucleotide-binding domain, and C-terminal leucine-rich repeats (LRRs), thought to function in a similar fashion to those found in Toll-like receptors. The primary role of this molecule appears to be regulation of the proteolytic processing of pro-IL-1β and pro-IL-18 into their mature forms via association in a large complex known as the inflammasome. Upon activation of Ipaf-1 by the intracellular bacterium S. typhimurium or other stress signals, Ipaf-1 recruits a CARD-containing adapter termed ASC and caspase-1 in unknown stoichiometry via CARD-CARD association. This complex in turn leads to autoproteolytic activation of caspase-1 and subsequent IL-1β and IL-18 maturation.
Antiviral signaling
Recently, a subset of CARD-containing proteins has been shown to participate in recognition of intracellular double-stranded
The adaptor protein VISA further activates the inhibitor of nuclear factor kappa-B kinase (IKK)-protein-kinase family members. Although the canonical IKK family members
Autoimmunity
Because of their role as regulators of inflammation, constitutive activation of certain CARD-containing proteins, either conferred by mutation or by constant presence of stress signals, has been suggested to play a causative role in a number of inflammatory syndromes. Gain-of-function mutations in the intracellular NOD2 protein has been linked to increased risk for
List of CARD-containing proteins
- BIRC2 baculoviral Inhibitor of apoptosis (IAP) repeat-containing 2, also known as C-IAP1 [1]
- BIRC3 baculoviral IAP repeat-containing 3, also known as C-IAP2 [2][permanent dead link]
- caspase-1: apoptosis-related cysteine peptidase (interleukin 1, beta, convertase; ICE) [3][permanent dead link]
- caspase-2: apoptosis-related cysteine peptidase [4][permanent dead link]
- caspase-4: apoptosis-related cysteine peptidase [5][permanent dead link]
- caspase-5: apoptosis-related cysteine peptidase [6][permanent dead link]
- caspase-9: apoptosis-related cysteine peptidase [7][permanent dead link]
- caspase-12: apoptosis-related cysteine peptidase [8][permanent dead link]
- caspase-13: apoptosis-related cysteine peptidase [9]
- ICEBERG: caspase-1 inhibitor iceberg [10]
- Pseudo-ICE: caspase-1 dominant-negative inhibitor Pseudo-ICE, also known as COP1 [11]
- MDA-5: Melanoma differentiation-associated protein 5, also called Interferon-induced helicase C domain-containing protein 1 (IFIH1) [12][permanent dead link]
- MAVS: Mitochondrial antiviral-signaling protein also known as CARD adapter inducing interferon-beta (Cardif/IPS-1) [13]
- CRADD: Caspase and RIP adapter with death domain also known as RIP-associated protein with a death domain (RAIDD) [14]
- RAIDD-2: Death adaptor molecule RAIDD-2 [15]
- DDX58) [16][permanent dead link]
- RIPK2: receptor-interacting serine-threonine kinase 2 (also called cardiak, RIP2 or RICK kinase) [17]
- BCL10: B-cell lymphoma/leukemia 10 protein [18][permanent dead link]
- BINCA: Bcl10-interacting CARD protein or BinCARD, also called chromosome 9 open reading frame 89 (C9orf89) [19][permanent dead link]
- CARD6: caspase recruitment domain family, member 6 [20][permanent dead link]
- CARD8/CARDINAL: caspase recruitment domain family, member 8 [21][permanent dead link]
- CARD9: caspase recruitment domain family, member 9 [22][permanent dead link]
- CARD10: caspase recruitment domain family, member 10 (also called CARMA3) [23][permanent dead link]
- CARD11: caspase recruitment domain family, member 11 (also called CARMA1) [24][permanent dead link]
- CARD14: caspase recruitment domain family, member 14 (also called CARMA2) [25][permanent dead link]
- APAF1: apoptotic peptidase activating factor 1 (also called CED4) [26][permanent dead link]
- GLAVA1: glavaris peptidase activating factor 1 (also called GLAV1) [27][permanent dead link]
- IPAF: Ice protease-activating factor, also known as NLR family, card domain containing 4 (NLRC4), CARD, LRR, and NACHT-containing protein (CLAN) and Caspase recruitment domain-containing protein 12 (CARD12) [28][permanent dead link]
- NOD1: nucleotide-binding oligomerization domain containing 1 [29][permanent dead link]
- NOD2: nucleotide-binding oligomerization domain containing 2 [30][permanent dead link]
- NLRC3: NOD-like receptor family CARD domain containing 3 [31][permanent dead link]
- NLRC5 It has also been called NOD27, NOD4, and CLR16.1
- NLRP1: NLR family, pyrin domain containing 1 (previously called NALP1) [32][permanent dead link]
- NOL3: nucleolar protein 3 (apoptosis repressor with CARD domain) [33][permanent dead link]
- PYCARD: PYD and CARD containing protein (also called ASC) [34][permanent dead link]
- Ced-3 analog of caspase-9 in Caenorhabditis elegans
- AIRE Autoimmune Regulator [35]
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References
- Hiscott J; et al. (2006). "MasterCARD: a priceless link to innate immunity". Trends Mol Med. 12 (2): 53–6. PMID 16406812.
- Ting JP, Williams KL (2005). "The CATERPILLER family: an ancient family of immune/apoptotic proteins". Clin Immunol. 115 (1): 33–7. PMID 15870018.
- Martinon F, Tschopp J (2004). "Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases". Cell. 117 (5): 561–74. S2CID 15140093.
- Hong GS, Junk YK (2002). "Caspase recruitment domain (CARD) as a bi-functional switch of caspase regulation and NF-kappaB signals". J Biochem Mol Biol. 35 (1): 19–23. PMID 16248965.
- Bouchier-Hayes L, Martin SJ (2002). "CARD games in apoptosis and immunity". EMBO Rep. 3 (7): 616–21. PMID 12101092.