| CARD14 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | CARD14 , BIMP2, CARMA2, PRP, PSORS2, PSS1, caspase recruitment domain family member 14 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607211 MGI: 2386258 HomoloGene: 11469 GeneCards: CARD14 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Caspase recruitment domain-containing protein 14, also known as D-containing MAGUK protein 2 (Carma 2), is a protein in the CARD-CC protein family that in humans is encoded by the CARD14 gene. [5] [6] [7]
The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD-CC protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD) and a coiled-coil (CC) domain. This protein thus shares a similar domain structure with the CARD10 and CARD11 proteins. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of NF-κB activation. The homotypic interaction with BCL10 is believed to be prevented by the linker region of CARD14, when in an inactive state. [8] CARD14 overexpression leads to an activation of the transcription factor NF-κB and phosphorylation of BCL10. CARD14 has been shown to form a CBM signalosome, similar to the signalling of CARD11, with BCL10 and MALT1. [5] [8]
The CARD14 gene was recently identified as the first gene directly linked to the most common form of Psoriasis. It has been suggested that a mutation in the gene plus an environmental trigger were enough to elicit plaque psoriasis. [9] [10] These rare, but highly penetrant, mutations were found to disrupt an auto-inhibited state of CARD14, which leads to the binding of BCL10 and the activation of NF-κB. [8]
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. CARD domains are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors.
NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28. Multiple transcript variants encoding different isoforms have been found for this gene.
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 present in birds.
TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.
IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the IKBKB gene.
The IκB kinase is an enzyme complex that is involved in propagating the cellular response to inflammation.
Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK-α has many additional cellular targets, and is thought to function independently of the NF-κB pathway to regulate epidermal differentiation.
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.
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK.
PYCARD, often referred to as ASC, is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome.
Receptor-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the RIPK2 gene.
Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.
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.
Caspase recruitment domain-containing protein 8 is a protein that in humans is encoded by the CARD8 gene.
Caspase recruitment domain-containing protein 10 is a protein in the CARD-CC protein family that in humans is encoded by the CARD10 gene.
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.
The nucleotide-binding oligomerization domain-like receptors, or NOD-like receptors (NLRs), are intracellular sensors of pathogen-associated molecular patterns (PAMPs) that enter the cell via phagocytosis or pores, and damage-associated molecular patterns (DAMPs) that are associated with cell stress. They are types of pattern recognition receptors (PRRs), and play key roles in the regulation of innate immune response. NLRs can cooperate with toll-like receptors (TLRs) and regulate inflammatory and apoptotic response. They are found in lymphocytes, macrophages, dendritic cells and also in non-immune cells, for example in epithelium. NLRs are highly conserved through evolution. Their homologs have been discovered in many different animal species (APAF1) and also in the plant kingdom.
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.
The CARD-CC protein family is defined by an evolutionary conserved CARD and a coiled-coil (CC) domain. 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. 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. In humans and other jawed vertebrates, the family consists of CARD9 and the three "CARD-containing MAGUK protein" (CARMA) proteins CARD11 (CARMA1), CARD14 (CARMA2) and CARD10 (CARMA3). 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. The four CARD-CC 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-hemapoetic cells. Interestingly is this gene expression differentiation between the four CARD-CC family members conserved at least as far back as frogs and fish, indicating that the four CARD-CC family members have had distinct functions since early jawed vertebrate evolution.
Autoinflammatory diseases (AIDs) are a group of rare disorders caused by dysfunction of the innate immune system. They are characterized by periodic or chronic systemic inflammation usually without the involvement of adaptive immunity.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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