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{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 <PDOC00430>) 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).
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{END}
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