The Complement subcomponents C1r/ C1s, sea urchin epidermal growth factor (Uegf), Bone morphogenetic protein 1 (Bmp1) domain (CUB domain) is a structural fold named after the first proteins in which it was identified .
The CUB domain is predominantly found in multicellular eukaryotes excluding fungi. However they are found in some unicellular plants and protozoa. The genomes of single celled alga and plankton as well as multicellular moss and poplar tree contain CUB proteins. There are few known CUB proteins from protozoa, however the parabasalid human parasite Trichomonas vaginalis expresses three proteins that contain a CUB domain and the slime mold Polysphondylium pallidum expresses a CUB protein. CUB domains appear to have been present in some of the earliest unicellular marine eukaryotes such as alga and plankton and have become established in multicellular eukaroytes.
There are examples of CUB domains in bacteria such as Clostridium perfringens  and archaea. The Clostridium perfringens and archaea CUB domain gene was probably obtained by horizontal gene transfer from a eukaryote .
Interestingly CUB domains have structural similarity to a number of viral capsid proteins including the small protein subunit of the bean-pod mottle virus (BPMV) capsid [3,4]. CUB domains and these capsid proteins may have evolved similar structures through convergent evolution .
Bork, P. and G. Beckmann, The CUB Domain : A Widespread Module in Developmentally Regulated Proteins. Journal of Molecular Biology, 1993. 231(2): p. 539-545.
- Briggs, D.C. and A.J. Day, A bug in CUB’s clothing: similarity between clostridial CBMs and complement CUBs. Trends in Microbiology, 2008. 16(9): p. 407-408.
- Varela, P.F., et al., The 2.4 Å resolution crystal structure of boar seminal plasma PSP-I/PSP-II: a zona pellucida-binding glycoprotein heterodimer of the spermadhesin family built by a CUB domain architecture. Journal of Molecular Biology, 1997. 274(4): p. 635-649.
- Romero, A., et al., The crystal structures of two spermadhesins reveal the CUB domain fold. Nat Struct Biol, 1997. 4(10): p. 783-8.