CARD-CC family

[5] 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).

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.

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.

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).