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Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases.

Ryu GM, Song P, Kim KW, Oh KS, Park KJ, Kim JH - Nucleic Acids Res. (2009)

Bottom Line: Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions.Therefore, a comparison of phosphovariants between individuals or between species can give clues about phenotypic differences.We categorized phosphovariants into three subtypes and developed a system that predicts them.

View Article: PubMed Central - PubMed

Affiliation: Center for Genome Science, 5 Nokbun-Dong, Eunpyung-Ku, Seoul, 122-701, Korea.

ABSTRACT
We define phosphovariants as genetic variations that change phosphorylation sites or their interacting kinases. Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions. Therefore, a comparison of phosphovariants between individuals or between species can give clues about phenotypic differences. We categorized phosphovariants into three subtypes and developed a system that predicts them. Our method can be used to screen important polymorphisms and help to identify the mechanisms of genetic diseases.

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Related in: MedlinePlus

Sequence logos of amino acid sequences near phosphorylation sites recognized by the CMGC kinase group. The horizontal axis represents sequential positions relative to the phosphorylation site. The vertical axis represents decreases in uncertainty. Each letter refers to an amino acid. As the frequency of an amino acid at a given position increases, its height increases.
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Figure 2: Sequence logos of amino acid sequences near phosphorylation sites recognized by the CMGC kinase group. The horizontal axis represents sequential positions relative to the phosphorylation site. The vertical axis represents decreases in uncertainty. Each letter refers to an amino acid. As the frequency of an amino acid at a given position increases, its height increases.

Mentions: It is more difficult to find examples of type II phosphovariants than to find type I phosphovariants, because we cannot definitely say that a phosphorylation site is changed by a substitution near a phosphorylation site. However, when some kinases (although not all kinases) recognize phosphorylation sites, the specific amino acids near the phosphoreceptor are important. In Figure 2, we present sequence logos of phosphorylation site sequences for the CMGC kinase group. The proline residues at position +1 relative to the phosphorylation sites are important in the phosphorylation site sequences of the CMGC kinase group, especially the CDK kinase family and the MAPK kinase family. Most (84%) of the phosphorylation sites of the CMGC group registered in the Swiss-Prot database and the Human Protein Resource Database (91% of the CDK and 87% of the MAPK kinase families) have +1 proline residues. If the proline is substituted with another amino acid, it is highly probable that the adjacent phosphorylation site will be abolished. The phosphorylation site at Ser112 of peroxisome proliferator-activated receptor gamma protein (Swiss-Prot ID, P37231) is eliminated by the Pro113Gln substitution (12). We found three other polymorphisms that abolish phosphorylation sites of the CMGC kinase group, but the removal of these phosphorylation sites has not yet been confirmed (Table 2). The presence of specific amino acids does not directly affect phosphorylation by kinases other than those of the CMGC kinase group, but sequences near the phosphorylation site must be considered. Kinases recognize the residues surrounding the target phosphorylation site, and the amino acids bordering phosphorylation sites are, in turn, affected by other nearby residues (13). Hence, when the relevant kinases are not members of the CMGC kinase group, it is difficult to predict type II phosphovariants simply by database matching, without specific programs that predict phosphorylation sites.Figure 2.


Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases.

Ryu GM, Song P, Kim KW, Oh KS, Park KJ, Kim JH - Nucleic Acids Res. (2009)

Sequence logos of amino acid sequences near phosphorylation sites recognized by the CMGC kinase group. The horizontal axis represents sequential positions relative to the phosphorylation site. The vertical axis represents decreases in uncertainty. Each letter refers to an amino acid. As the frequency of an amino acid at a given position increases, its height increases.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651802&req=5

Figure 2: Sequence logos of amino acid sequences near phosphorylation sites recognized by the CMGC kinase group. The horizontal axis represents sequential positions relative to the phosphorylation site. The vertical axis represents decreases in uncertainty. Each letter refers to an amino acid. As the frequency of an amino acid at a given position increases, its height increases.
Mentions: It is more difficult to find examples of type II phosphovariants than to find type I phosphovariants, because we cannot definitely say that a phosphorylation site is changed by a substitution near a phosphorylation site. However, when some kinases (although not all kinases) recognize phosphorylation sites, the specific amino acids near the phosphoreceptor are important. In Figure 2, we present sequence logos of phosphorylation site sequences for the CMGC kinase group. The proline residues at position +1 relative to the phosphorylation sites are important in the phosphorylation site sequences of the CMGC kinase group, especially the CDK kinase family and the MAPK kinase family. Most (84%) of the phosphorylation sites of the CMGC group registered in the Swiss-Prot database and the Human Protein Resource Database (91% of the CDK and 87% of the MAPK kinase families) have +1 proline residues. If the proline is substituted with another amino acid, it is highly probable that the adjacent phosphorylation site will be abolished. The phosphorylation site at Ser112 of peroxisome proliferator-activated receptor gamma protein (Swiss-Prot ID, P37231) is eliminated by the Pro113Gln substitution (12). We found three other polymorphisms that abolish phosphorylation sites of the CMGC kinase group, but the removal of these phosphorylation sites has not yet been confirmed (Table 2). The presence of specific amino acids does not directly affect phosphorylation by kinases other than those of the CMGC kinase group, but sequences near the phosphorylation site must be considered. Kinases recognize the residues surrounding the target phosphorylation site, and the amino acids bordering phosphorylation sites are, in turn, affected by other nearby residues (13). Hence, when the relevant kinases are not members of the CMGC kinase group, it is difficult to predict type II phosphovariants simply by database matching, without specific programs that predict phosphorylation sites.Figure 2.

Bottom Line: Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions.Therefore, a comparison of phosphovariants between individuals or between species can give clues about phenotypic differences.We categorized phosphovariants into three subtypes and developed a system that predicts them.

View Article: PubMed Central - PubMed

Affiliation: Center for Genome Science, 5 Nokbun-Dong, Eunpyung-Ku, Seoul, 122-701, Korea.

ABSTRACT
We define phosphovariants as genetic variations that change phosphorylation sites or their interacting kinases. Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions. Therefore, a comparison of phosphovariants between individuals or between species can give clues about phenotypic differences. We categorized phosphovariants into three subtypes and developed a system that predicts them. Our method can be used to screen important polymorphisms and help to identify the mechanisms of genetic diseases.

Show MeSH
Related in: MedlinePlus