Naked cuticle (Nkd) is a conserved family of intracellular proteins encoded in most animal genomes.
[citation needed] In Drosophila, nkd is a segment–polarity class gene that limits the spatial extent of Wnt signaling pathway activity, similar to how the Patched (Ptc) gene regulates the Hedgehog signaling pathway; i.e., Nkd and Ptc shape tissue gradients of Wnt and Hedgehog signaling.
[3] Nkd proteins consist of at least four well-conserved blocks of amino acid sequence interspersed by variable regions.
[4][5] The conserved sequence blocks, from N-terminal to C-terminal, are as follows: 1) a N-terminal membrane anchoring motif, which in mammals is subject to myristoylation;[6][7] 2) a single, extended EF hand motif (called "EFX" or "NH2") that binds Dsh/Dvl proteins;[4][8] 3) a thirty amino acid amphipathic alpha helix motif that in the fly Nkd protein mediates nuclear translocation[9] and that in the human Nkd1 protein interferes with the interaction between the EF-hand motif and Dvl proteins;[10] and 4) a C-terminal Histidine-rich sequence of unknown function.
For example, Nkd2 but not Nkd1 associates with the secreted EGF-family ligand TGF alpha via a sequence between the third and fourth block that is only in Nkd2,[6] and a sequence between the third and fourth block that is highly conserved in Drosophila species but is neither present in the more distantly related mosquito Anopheles gambiae Nkd nor in any known vertebrate Nkds mediates nuclear import via binding to the nuclear import factor importin-alpha3.