Kinase Family RIPK
Kinase Classification: Group TKL: Family RIPK
Receptor Interacting Protein Kinases (RIPK) interact with TNF and other death receptors and transduce their signals.
Evolution
RIPK are clearly found in vertebrates and other chordates [1]. Arthropods appear to have a RIPK1 homolog that lacks the kinase domain (e.g. Drosophila imd) and mollusks such as Crassostrea gigas also have a likely RIPK gene.
Domain Structure
All vertebrate RIPK have an N-terminal TKL kinase domain, and a long C-terminal extension that contains one of several interaction domains. RIPK1 has a death domain and an RHIM motif. RIPK3 has the RHIM but no death domain, and RIPK2 has a CARD domain, which is related to the death domain. SgK288 and RIPK4 (ANKRD3) both have an array of ankyrin repeats.
Invertebrate RIPKs have more divergent domain architectures. Arthopods have the imd (immune defective) protein that has a RIPK-like death domain but has no kinase domain, while urchin and lancelet homologs have Leucine Rich Repeats or Ankyrin repeats that are N-terminal of the kinase domain, and a Ciona homolog has C-terminal Sushi domains.
Subfamilies
RIPKs are fast-evolving and difficult to classify, but most fall into one of two types - those with ankyrin repeats (Subfamily RIPK-A) and those with Death (or the related CARD) domain, (Subfamily RIPK-D).
