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 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
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]