CARD-CC family

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The CARD-CC protein family is defined by an evolutionary conserved "caspase activation and recruitment domain" (CARD) and a coiled-coil (CC) domain. [1] [2] Coiled-coils (CC) act as oligomerization domains for many proteins such as structural and motor proteins, and transcription factors. This means that monomers are converted to macromolecular complexes by polymerization. [3] In humans and other jawed vertebrates, the family consists of CARD9 and the three "CARD-containing MAGUK protein" (CARMA) [4] proteins CARD11 (CARMA1), CARD14 (CARMA2) and CARD10 (CARMA3). Although the MAGUK protein DLG5 contains both a CARD domain and a CC domain, it does not belong to the same family as the CARD-CC proteins since the evolutionary origin of its CARD domain is very likely to be different. [5]

Contents

CARD-CC protein family structure CARD-CC family structure.svg
CARD-CC protein family structure

Evolution and species distribution

The protein family is ancient and can be found as far back as Cnidaria, but has almost exclusively been studied in humans and mice. Notably, the protein family is absent in insects and nematodes, which makes it impossible to study its function in the most popular invertebrate model organisms (Drosophila and C. elegans). Invertebrates only have a CARD9-like ancestral CARD-CC member, and the earliest occurrence of a CARD-CC member with the CARMA domain composition is in the jawless vertebrate hagfish. Already in sharks are all four CARD-CC family members present, indicating that the 3 distinct CARMA CARD-CC family members were formed by two duplication events just before or very early in the jawed vertebrate evolution, almost half a billion years ago. The four CARD-CC ohnologous members in mice and humans differ in expression domains, where CARD9 is mostly expressed in myelocytes, CARD11 in lymphocytes, while CARD10 and CARD14 are mostly expressed in non-haematopoetic cells. This gene expression differentiation between the four CARD-CC family members conserved at least as far back as frogs (Xenopus tropicalis) and fish (Danio rerio), [6] indicating that the four CARD-CC family members have had distinct functions since early jawed vertebrate evolution.

Functions

A common theme for all four CARD-CC family proteins in mice and humans is that they are activated by different protein kinase C isoforms, [7] and recruit BCL10 and the paracaspase MALT1 upon activation, forming a so-called CBM complex. There are four different CBM complexes, defined by which CARD-CC family member that is responsible for its assembly: CBM-9 (CARD9), CBM-1 (CARD11/CARMA1), CBM-2 (CARD14/CARMA2) and CBM-3 (CARD10/CARMA3). [8] CBM complex assembly results in recruitment of TRAF6 to MALT1 and downstream activation of NF-κB transcriptional activity and expression of pro-inflammatory cytokines. The different CARD-CC family members show different expression pattern and gain- or loss of function mutation in the different CARD-CC family proteins cause different phenotypes.

Graphical overview of signaling pathways dependent on a CARD-CC family member CARD-CC signaling.svg
Graphical overview of signaling pathways dependent on a CARD-CC family member

Related Research Articles

<span class="mw-page-title-main">CARD (domain)</span> Interaction motifs found in a wide array of proteins

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.

<span class="mw-page-title-main">NLRP3</span> Human protein and coding gene

NLR family pyrin domain containing 3 (NLRP3), is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1.

<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.

<span class="mw-page-title-main">Tyrosine-protein kinase SYK</span>

Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene.

Paracaspases are members of the C14 family of cysteine proteases. Paracaspases are proteins related to caspases present in animals and slime mold, in contrast to metacaspases, which are present in plants, fungi, and "protists". The phylogenetic distribution is a bit confusing, since slime mold diverged earlier than the animal/fungal split.

<span class="mw-page-title-main">BCL10</span> Protein-coding gene in the species Homo sapiens

B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the BCL10 gene. Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma.

<span class="mw-page-title-main">CD244</span> Protein found in humans

CD244 also known as 2B4 or SLAMF4 is a protein that in humans is encoded by the CD244 gene.

<span class="mw-page-title-main">CLEC7A</span> Protein-coding gene in humans

C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

<span class="mw-page-title-main">CARD11</span> Protein-coding gene in the species Homo sapiens

Caspase recruitment domain-containing protein 11 also known as CARD-containing MAGUK protein 1 is a protein in the CARD-CC protein family that in humans is encoded by the CARD11 gene. CARD 11 is a membrane associated protein that is found in various human tissues, including the thymus, spleen, liver, and peripheral blood leukocytes. Similarly, CARD 11 is also found in abundance in various lines of cancer cells.

<span class="mw-page-title-main">MDA5</span> Mammalian protein found in Homo sapiens

MDA5 is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses. It is generally believed that MDA5 recognizes double stranded RNA (dsRNA) over 2000nts in length, however it has been shown that whilst MDA5 can detect and bind to cytoplasmic dsRNA, it is also activated by a high molecular weight RNA complex composed of ssRNA and dsRNA. For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2. The signaling cascades in MDA5 is initiated via CARD domain. Some observations made in cancer cells show that MDA5 also interacts with cellular RNA is able to induce an autoinflammatory response.

<span class="mw-page-title-main">CARD10</span> Protein-coding gene in the species Homo sapiens

Caspase recruitment domain-containing protein 10 is a protein in the CARD-CC protein family that in humans is encoded by the CARD10 gene.

<span class="mw-page-title-main">MALT1</span> Protein-coding gene in the species Homo sapiens

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 is a protein that in humans is encoded by the MALT1 gene. It's the human paracaspase.

<span class="mw-page-title-main">CARD9</span> Protein-coding gene in the species Homo sapiens

Caspase recruitment domain-containing protein 9 is an adaptor protein of the CARD-CC protein family, which in humans is encoded by the CARD9 gene. It mediates signals from pattern recognition receptors to activate pro-inflammatory and anti-inflammatory cytokines, regulating inflammation. Homozygous mutations in CARD9 are associated with defective innate immunity against yeasts, like Candida and dermatophytes.

<span class="mw-page-title-main">Pyrin domain</span>

A pyrin domain is a protein domain and a subclass of protein motif known as the death fold, the 4th and most recently discovered member of the death domain superfamily (DDF). It was originally discovered in the pyrin protein, or marenostrin, encoded by MEFV. The mutation of the MEFV gene is the cause of the disease known as Familial Mediterranean Fever. The domain is encoded in 23 human proteins and at least 31 mouse genes.

<span class="mw-page-title-main">CARD14</span> Protein-coding gene in the species Homo sapiens

Caspase recruitment domain-containing protein 14, also known as D-containing MAGUK protein 2, is a protein in the CARD-CC protein family that in humans is encoded by the CARD14 gene.

Immunogenic cell death is any type of cell death eliciting an immune response. Both accidental cell death and regulated cell death can result in immune response. Immunogenic cell death contrasts to forms of cell death that do not elicit any response or even mediate immune tolerance.

<span class="mw-page-title-main">BENTA disease</span> Medical condition

BENTA disease is a rare genetic disorder of the immune system. BENTA stands for "B cell expansion with NF-κB and T cell anergy" and is caused by germline heterozygous gain-of-function mutations in the gene CARD11. This disorder is characterized by polyclonal B cell lymphocytosis with onset in infancy, splenomegaly, lymphadenopathy, mild immunodeficiency, and increased risk of lymphoma. Investigators Andrew L. Snow and Michael J. Lenardo at the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health first characterized BENTA disease in 2012. Dr. Snow's current laboratory at the Uniformed Services University of the Health Sciences is now actively studying this disorder.

<span class="mw-page-title-main">BinCARD</span> Protein-coding gene in the species Homo sapiens

Bcl10-interacting CARD protein, also known as BinCARD, is a protein that in humans is encoded by the C9orf89 gene on chromosome 9. BinCARD is a member of the death-domain superfamily and contains a caspase recruitment domain (CARD). This protein regulates apoptosis and the immune response by inhibiting Bcl10, thus implicating it in diseases stemming from Bcl10 dysfunction.

<span class="mw-page-title-main">CLEC6A</span> Protein-coding gene in humans

Dectin-2 or C-type lectin domain containing 6A is a protein that in humans is encoded by the CLEC6A gene. Dectin-2 is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded protein is a type II transmembrane protein with an extracellular carbohydrate recognition domain. It functions as a pattern recognition receptor recognizing α-mannans and as such plays an important role in innate immune response to fungi. Expression is found on macrophages and dendritic cells. It can also be found at low levels in Langerhans cells and peripheral blood monocytes, where expression levels could be increased upon induction of inflammation.

Not to be confused with Autoimmune disease.

References

  1. ↑ Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (2018). "Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi: 10.3389/fimmu.2018.01136 . PMC   5978004 . PMID   29881386.
  2. ↑ Bouchier-Hayes, Lisa; Martin, Seamus J (July 2002). "CARD games in apoptosis and immunity". EMBO Reports. 3 (7): 616–621. doi:10.1093/embo-reports/kvf139. ISSN   1469-221X. PMC   1084193 . PMID   12101092 . Retrieved 2023-09-11.
  3. ↑ "CC Protein Domain | Coiled Coil | Cell Signaling Technology". www.cellsignal.com. Retrieved 2020-02-01.
  4. ↑ Scudiero I, Vito P, Stilo R (August 2014). "The three CARMA sisters: so different, so similar: a portrait of the three CARMA proteins and their involvement in human disorders". Journal of Cellular Physiology. 229 (8): 990–7. doi:10.1002/jcp.24543. PMID   24375035. S2CID   45905503.
  5. ↑ Friedrichs, Frauke; Henckaerts, Liesbet; Vermeire, Severine; Kucharzik, Torsten; Seehafer, Tanja; Möller-Krull, Maren; Bornberg-Bauer, Erich; Stoll, Monika; Weiner, January (2008-04-01). "The Crohn's disease susceptibility gene DLG5 as a member of the CARD interaction network". Journal of Molecular Medicine. 86 (4): 423–432. doi:10.1007/s00109-008-0307-5. ISSN   1432-1440. PMID   18335190. S2CID   24982374 . Retrieved 2023-09-11.
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  8. ↑ Gehring, Torben; Seeholzer, Thomas; Krappmann, Daniel (2018). "BCL10 – Bridging CARDs to Immune Activation". Frontiers in Immunology. 9: 1539. doi: 10.3389/fimmu.2018.01539 . ISSN   1664-3224. PMC   6039553 . PMID   30022982.
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  17. ↑ Online Mendelian Inheritance in Man (OMIM): 607211
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  19. ↑ McAuley JR, Freeman TJ, Ekambaram P, Lucas PC, McAllister-Lucas LM (2018). "CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis". Frontiers in Immunology. 9: 1887. doi: 10.3389/fimmu.2018.01887 . PMC   6104486 . PMID   30158935.
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