Caspase recruitment domain-containing protein 14, also known as CARD-containing MAGUK protein 2 (Carma 2), is a protein in the CARD-CC protein family that in humans is encoded by the CARD14gene.[5][6][7]
Function
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 cell apoptosis and 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]
Link to Psoriasis
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]
^Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES (April 2001). "CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B". J. Biol. Chem. 276 (15): 11877–82. doi:10.1074/jbc.M010512200. PMID11278692.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^Gaide O, Martinon F, Micheau O, Bonnet D, Thome M, Tschopp J (May 2001). "Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation". FEBS Lett. 496 (2–3): 121–7. doi:10.1016/S0014-5793(01)02414-0. PMID11356195.