{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 *
******************************************

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}
