Kinase Family DDR
Kinase Classification: Group TK: Family DDR
These receptor tyrosine kinases uniquely recognize and signal downstream of extracellular collagen.
Evolution
DDRs are found in all animals, but not elsewhere. Two forms (DDR1 and DDR2) are found in mammals, and nematodes also have a duplication.
Domain Structure
DDRs have a typical RTK structure: a signal peptide, followed by an extracellular region, a transmembrane domain and an intracellular kinase domain. The extracellular domain has a single defined domain, the discoidin domain (F5_F8_type_C in Pfam parlance), which mediates collagen-binding. Conserved residues within the transmembrane domain appear to mediate dimerization.
The only exception to this structure is in sponge (Amphimedon) where 8 putative DDRs are found. These either have Ig domains in their extracellular regions, or are fragments; however, their kinase domains are most similar to eumetazoan DDRs, and so likely have similar downstream signaling pathways (sponges have some but not all types of collagen seen in eumetazoans [1]).
Function
DDRs serve as receptors for various forms of collagen.
References
- Exposito JY, Larroux C, Cluzel C, Valcourt U, Lethias C, and Degnan BM. Demosponge and sea anemone fibrillar collagen diversity reveals the early emergence of A/C clades and the maintenance of the modular structure of type V/XI collagens from sponge to human. J Biol Chem. 2008 Oct 17;283(42):28226-35. DOI:10.1074/jbc.M804573200 |
