Phylogenetic analysis of the cadherin superfamily allows identification ofsix major subfamilies besides several solitary members

Cadherins play an important role in specific cell-cell adhesion events. The ir expression appears to be tightly regulated during development and each t issue or cell type shows a characteristic pattern of cadherin molecules. In appropriate regulation of their expression levels or functionality has been observed in human malignancies, in many cases leading to aggravated cancer cell invasion and metastasis. The cadherins form a superfamily with at lea st six subfamilies, which can be distinguished on the basis of protein doma in composition, genomic structure, and phylogenetic analysis of the protein sequences. These subfamilies comprise classical or type-I cadherins, atypi cal or type-II cadherins, desmocollins, desmogleins, protocadherins and Fla mingo cadherins. In addition, several cadherins clearly occupy isolated pos itions in the cadherin superfamily (cadherin-13, -15, -16, -17, Dachsous, R ET, FAT, MEGF1 and most invertebrate cadherins). We suggest a different evo lutionary origin of the protocadherin and Flamingo cadherin genes versus th e genes encoding desmogleins, desmocollins, classical cadherins, and atypic al cadherins, The present phylogenetic analysis may accelerate the function al investigation of the whole cadherin superfamily by allowing focused rese arch of prototype cadherins within each subfamily. (C) 2000 Academic Press.