PROSITE: PDOC00100 (documentation)
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{PDOC00100}
{PS00107; PROTEIN_KINASE_ATP}
{PS00108; PROTEIN_KINASE_ST}
{PS00109; PROTEIN_KINASE_TYR}
{PS50011; PROTEIN_KINASE_DOM}
{BEGIN}
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* Protein kinases signatures and profile *
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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 <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].
-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).
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