SMART
Taken from the SMART web site (link):
"Accurate multiple alignments of 86 domains that occur in signalling proteins have been constructed and used to provide a WEB-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signalling domain sequences.
The majority of signalling proteins are multidomain in character with a considerable variety of domain combinations known.
Comparison with established collections of domain patterns and alignments showed that 25% of our domain set could not be deduced from sequence database entries and 41% could not be annotated by Pfam.
SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signalling domains, approximately 350 greater than previously annotated.
The process of constructing the search tool predicted:
  1. additional homologues of previously-described domains in unexpected locations such as a band 4.1-homologous domain in focal adhesion kinase;
  2. previously-unknown domain families including a "CNH" or citron-homology domain and a domain preceding rasGEF-like guanine nucleotide exchange factor regions;
  3. candidate functions of domain families following identification of additional family members, for example, a ubiquitin-binding role for the UBA domain;
  4. cellular roles for proteins, such as the detection of a DEATH domain in netrin receptors further implicating these molecules in axonal guidance;
  5. signalling domains in known disease genes such as a SPRY domain in marenostrin/pyrin that is mutated in patients with Mediterranean fever;
  6. domains in unexpected phylogenetic contexts such as DAG kinase homologues in yeast and bacteria;
  7. likely misclassifications of proteins exemplified by the presence of a pleckstrin homology signalling domain in a C. albicans protein, previously described as an integrin."
SMART Glossary
References

Schultz J, Milpetz F, Bork P, Ponting CP (1998) SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci U S A 95(11):5857-64 (abstract - full paper)

Ponting,C.P., Schultz,J.,Milpetz,F. & Bork,P. (1999). SMART: identification and annotation of domains from signalling and extracellular protein sequences. NAR, 27, 229-232 (abstract)