Sequence difference among different types of the ADAM family. ADAM members have four types. In Type I ADAMs the metalloprotease M-domain has the characteristic catalytic Zn2+ binding signature (HExGHxxGxxHD), and the disintegrin D-domain is based on xCD sequence. In Type II ADAMs the M-domain does not have the characteristic catalytic-Zn2+ binding signature and is more variable compared to Type I. In Type III ADAMs the M-domain contains the characteristic catalytic-Zn2+ binding signature, but similar to SVM, the D-domain is based on RGD sequence rather than the xCD sequence in most ADAMs. In Type IV ADAMs the D-domain is based on xCD sequence, but they lack the EGF-like region found in Type I, II, and III.