PROSITE documentation PDOC00100

Protein kinases signatures and profile

Description

Eukaryotic protein kinases [1,2,3,4,5] 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.

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.
 Quinn A.M.

Last update:

April 2006 / Pattern revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

PROTEIN_KINASE_DOM, PS50011; Protein kinase domain profile  (MATRIX)
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.
• Domain architecture view of Swiss-Prot proteins matching PS50011
PS50011
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50011
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50011
• Scan Swiss-Prot/TrEMBL entries against PS50011
• view ligand binding statistics
Matching PDB structures: 1A06 1A9U 1AD5 1AGW ... [ALL]
PROTEIN_KINASE_ATP, PS00107; Protein kinases ATP-binding region signature  (PATTERN)
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.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00107
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00107
• Scan Swiss-Prot/TrEMBL entries against PS00107
• view ligand binding statistics
Matching PDB structures: 1A9U 1AD5 1AGW 1APM ... [ALL]
PROTEIN_KINASE_ST, PS00108; Serine/Threonine protein kinases active-site signature  (PATTERN)
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.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00108
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00108
• Scan Swiss-Prot/TrEMBL entries against PS00108
• view ligand binding statistics
Matching PDB structures: 1A06 1APM 1AQ1 1ATP ... [ALL]
PROTEIN_KINASE_TYR, PS00109; Tyrosine protein kinases specific active-site signature  (PATTERN)
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.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00109
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00109
• Scan Swiss-Prot/TrEMBL entries against PS00109
• view ligand binding statistics
Matching PDB structures: 1AD5 1AGW 1BYG 1FGI ... [ALL]

References

1 Authors Hanks S.K., Hunter T.
Title Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
Source FASEB J. 9:576-596(1995).
PubMed ID 7768349
2 Authors Hunter T.
Title Protein kinase classification.
Source Methods Enzymol. 200:3-37(1991).
PubMed ID 1835513
3 Authors Hanks S.K., Quinn A.M.
Title Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members.
Source Methods Enzymol. 200:38-62(1991).
PubMed ID 1956325
4 Authors Hanks S.K.
Source Curr. Opin. Struct. Biol. 1:369-383(1991).
5 Authors Hanks S.K., Quinn A.M., Hunter T.
Title The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
Source Science 241:42-52(1988).
PubMed ID 3291115
6 Authors Knighton D.R., Zheng J.H., Ten Eyck L.F., Ashford V.A., Xuong N.-H., Taylor S.S., Sowadski J.M.
Title Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
Source Science 253:407-414(1991).
PubMed ID 1862342
7 Authors Bairoch A., Claverie J.-M.
Title Sequence patterns in protein kinases.
Source Nature 331:22-22(1988).
PubMed ID 3340146
DOI 10.1038/331022a0
8 Authors Benner S.
Source Nature 329:21-21(1987).
9 Authors Kirby R.
Title Evolutionary origin of aminoglycoside phosphotransferase resistance genes.
Source J. Mol. Evol. 30:489-492(1990).
PubMed ID 2165531
10 Authors Littler E., Stuart A.D., Chee M.S.
Source Nature 358:160-162(1992).
11 Authors Munoz-Dorado J., Inouye S., Inouye M.
Source Cell 67:995-1006(1991).

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