Trends in Biochemical Sciences
Protein Sequence MotifThe KIND module: a putative signalling domain evolved from the C lobe of the protein kinase fold
Section snippets
Sequence analysis of the Spir protein N-terminal region
To elucidate the features of the Spir N-terminal sequence, a search of the non-redundant protein database with PSI–BLAST [6] using the first 350 residues of Dm p150-Spir was performed. The putative orthologues in Anopheles gambiae (EAA12347, E = 10−23), Homo sapiens (Spir-1, BAA86449, E = 10−13; Spir-2, CAD19439, E = 10−7), Rattus norvegicus (Spir-1, XP_225864, E = 10−13; Spir-2, XP_226553, E = 10−6) and Mus musculus (Spir-1, XP_140409, E = 10−11; Spir-2, CAD30509, E = 10−7) genomes were first
Evolutionary relationship between the new domain and the catalytic region of the kinase fold
The protein kinases, which all transfer the γ-phosphate from ATP to a receiving hydroxyl group of the target protein but differ in the activation and/or inactivation processes, represent one of the most abundant families in the eukaryotic genomes [8]. Multiple sequence alignments of some representatives of the different protein kinase subfamilies identified 11 major conserved motifs 9, 10. The first 3D structure solved, that of the Ser/Thr protein kinase A (PKA) [11], showed those motifs as
Functional implications
The precise functional role of the KIND domain remains to be elucidated, although interesting hypotheses can be formulated from the analysis of the protein families bearing it. The C-lobe domain mediates the interaction of kinases with activators, substrates and regulatory subunits 20, 21, suggesting an interaction role for the KIND domain. It is known that the C-terminal region of p150-Spir protein interacts with the MAP kinase JNK [1]. The N-terminal KIND domain of the Spir proteins could
Acknowledgements
E.K. was supported by funds from the Deutsche Forschungsgemeinschaft (DFG KE 447/3-2) and the Wilhelm Sander-Stiftung (2002.012.1).
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