{PDOC00100} {PS00107; PROTEIN_KINASE_ATP} {PS00108; PROTEIN_KINASE_ST} {PS00109; PROTEIN_KINASE_TYR} {PS50011; PROTEIN_KINASE_DOM} {BEGIN} ****************************************** * Protein kinases signatures and profile * ****************************************** Eukaryotic protein kinases [1 to 5] are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common to both serine/threonine and tyrosine protein kinases. There are a number of conserved regions in the catalytic domain of protein kinases. We have selected two of these regions to build signature patterns. The first region, which is located in the N-terminal extremity of the catalytic domain, is a glycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involved in ATP binding. The second region, which is located in the central part of the catalytic domain, contains a conserved aspartic acid residue which is important for the catalytic activity of the enzyme [6]; we have derived two signature patterns for that region: one specific for serine/ threonine kinases and the other for tyrosine kinases. We also developed a profile which is based on the alignment in [1] and covers the entire catalytic domain. -Consensus pattern: [LIV]-G-{P}-G-{P}-[FYWMGSTNH]-[SGA]-{PW}-[LIVCAT]-{PD}-x- [GSTACLIVMFY]-x(5,18)-[LIVMFYWCSTAR]-[AIVP]-[LIVMFAGCKR]-K [K binds ATP] -Sequences known to belong to this class detected by the pattern: the majority of known protein kinases but it fails to find a number of them, especially viral kinases which are quite divergent in this region and are completely missed by this pattern. -Other sequence(s) detected in Swiss-Prot: 42. -Consensus pattern: [LIVMFYC]-x-[HY]-x-D-[LIVMFY]-K-x(2)-N-[LIVMFYCT](3) [D is an active site residue] -Sequences known to belong to this class detected by the pattern: Most serine/ threonine specific protein kinases with 10 exceptions (half of them viral kinases) and also Epstein-Barr virus BGLF4 and Drosophila ninaC which have respectively Ser and Arg instead of the conserved Lys and which are therefore detected by the tyrosine kinase specific pattern described below. -Other sequence(s) detected in Swiss-Prot: 1. -Consensus pattern: [LIVMFYC]-{A}-[HY]-x-D-[LIVMFY]-[RSTAC]-{D}-{PF}-N- [LIVMFYC](3) [D is an active site residue] -Sequences known to belong to this class detected by the pattern: ALL tyrosine specific protein kinases with the exception of human ERBB3 and mouse blk. This pattern will also detect most bacterial aminoglycoside phosphotransferases [8,9] and herpesviruses ganciclovir kinases [10]; which are proteins structurally and evolutionary related to protein kinases. -Other sequence(s) detected in Swiss-Prot: 17. -Sequences known to belong to this class detected by the profile: ALL, except for three viral kinases. This profile also detects receptor guanylate cyclases (see ) and 2-5A-dependent ribonucleases. Sequence similarities between these two families and the eukaryotic protein kinase family have been noticed before. It also detects Arabidopsis thaliana kinase- like protein TMKL1 which seems to have lost its catalytic activity. -Other sequence(s) detected in Swiss-Prot: 4. -Note: If a protein analyzed includes the two protein kinase signatures, the probability of it being a protein kinase is close to 100% -Note: Eukaryotic-type protein kinases have also been found in prokaryotes such as Myxococcus xanthus [11] and Yersinia pseudotuberculosis. -Note: The patterns shown above has been updated since their publication in [7]. -Expert(s) to contact by email: Hunter T.; hunter@salk-sc2.sdsc.edu Quinn A.M.; quinn@biomed.med.yale.edu -Last update: April 2006 / Pattern revised. [ 1] Hanks S.K., Hunter T. "Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification." FASEB J. 9:576-596(1995). PubMed=7768349 [ 2] Hunter T. "Protein kinase classification." Methods Enzymol. 200:3-37(1991). PubMed=1835513 [ 3] Hanks S.K., Quinn A.M. "Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members." Methods Enzymol. 200:38-62(1991). PubMed=1956325 [ 4] Hanks S.K. Curr. Opin. Struct. Biol. 1:369-383(1991). [ 5] Hanks S.K., Quinn A.M., Hunter T. "The protein kinase family: conserved features and deduced phylogeny of the catalytic domains." Science 241:42-52(1988). PubMed=3291115 [ 6] Knighton D.R., Zheng J.H., Ten Eyck L.F., Ashford V.A., Xuong N.-H., Taylor S.S., Sowadski J.M. "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase." Science 253:407-414(1991). PubMed=1862342 [ 7] Bairoch A., Claverie J.-M. "Sequence patterns in protein kinases." Nature 331:22-22(1988). PubMed=3340146; DOI=10.1038/331022a0 [ 8] Benner S. Nature 329:21-21(1987). [ 9] Kirby R. "Evolutionary origin of aminoglycoside phosphotransferase resistance genes." J. Mol. Evol. 30:489-492(1990). PubMed=2165531 [10] Littler E., Stuart A.D., Chee M.S. Nature 358:160-162(1992). [11] Munoz-Dorado J., Inouye S., Inouye M. Cell 67:995-1006(1991). -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}