{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 bythis pattern. -Other sequence(s) detected in SWISS-PROT: 35. -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]-x-[HY]-x-D-[LIVMFY]-[RSTAC]-x(2)-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: 15. -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]. -Note: this documentation entry is linked to both signature patterns and a profile. As the profile is much more sensitive than the patterns, you should use it if you have access to the necessary software tools to do so. -Expert(s) to contact by email: Hunter T.; hunter@salk-sc2.sdsc.edu Quinn A.M.; quinn@biomed.med.yale.edu -Last update: November 1995 / Patterns and text revised; profile added. [ 1] Hanks S.K., Hunter T. FASEB J. 9:576-596(1995). [ 2] Hunter T. Meth. Enzymol. 200:3-37(1991). [ 3] Hanks S.K., Quinn A.M. Meth. Enzymol. 200:38-62(1991). [ 4] Hanks S.K. Curr. Opin. Struct. Biol. 1:369-383(1991). [ 5] Hanks S.K., Quinn A.M., Hunter T. Science 241:42-52(1988). [ 6] Knighton D.R., Zheng J., Ten Eyck L.F., Ashford V.A., Xuong N.-H., Taylor S.S., Sowadski J.M. Science 253:407-414(1991). [ 7] Bairoch A., Claverie J.-M. Nature 331:22(1988). [ 8] Benner S. Nature 329:21-21(1987). [ 9] Kirby R. J. Mol. Evol. 30:489-492(1992). [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). +----------------------------------------------------------------------------+ | This PROSITE entry is copyright by the Swiss Institute of Bioinformatics | | (SIB). There are no restrictions on its use by non-profit institutions as | | long as its content is in no way modified and this statement is not | | removed. 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