The importance of intrinsic disorder for protein phosphorylation

被引:1118
作者
Iakoucheva, LM
Radivojac, P
Brown, CJ
O'Connor, TR
Sikes, JG
Obradovic, Z
Dunker, AK
机构
[1] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
[2] Temple Univ, Ctr Informat Sci & Technol, Philadelphia, PA 19122 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1093/nar/gkh253
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reversible protein phosphorylation provides a major regulatory mechanism in eukaryotic cells. Due to the high variability of amino acid residues flanking a relatively limited number of experimentally identified phosphorylation sites, reliable prediction of such sites still remains an important issue. Here we report the development of a new web-based tool for the prediction of protein phosphorylation sites, DISPHOS (DiSorder-enhanced PHOSphorylation predictor, hftp://www.ist.temple.edu/DISPHOS). We observed that amino acid compositions, sequence complexity, hydrophobicity, charge and other sequence attributes of regions adjacent to phosphorylation sites are very similar to those of intrinsically disordered protein regions. Thus, DISPHOS uses position-specific amino acid frequencies and disorder information to improve the discrimination between phosphorylation and nonphosphorylation sites. Based on the estimates of phosphorylation rates in various protein categories, the outputs of DISPHOS are adjusted in order to reduce the total number of misclassified residues. When tested on an equal number of phosphorylated and non-phosphorylated residues, the accuracy of DISPHOS reaches 76% for serine, 81% for threonine and 83% for tyrosine. The significant enrichment in disorder-promoting residues surrounding phosphorylation sites together with the results obtained by applying DISPHOS to various protein functional classes and proteomes, provide strong support for the hypothesis that protein phosphorylation predominantly occurs within intrinsically disordered protein regions.
引用
收藏
页码:1037 / 1049
页数:13
相关论文
共 65 条
  • [1] PROTEIN HISTIDINE KINASES AND SIGNAL-TRANSDUCTION IN PROKARYOTES AND EUKARYOTES
    ALEX, LA
    SIMON, MI
    [J]. TRENDS IN GENETICS, 1994, 10 (04) : 133 - 138
  • [2] Belsley DA, 1980, Regression Diagnostics: Identifying Influential Data and Sources of Collinearity
  • [3] Functional consequences of preorganized helical structure in the intrinsically disordered cell-cycle inhibitor p27Kip1
    Bienkiewicz, EA
    Adkins, JN
    Lumb, KJ
    [J]. BIOCHEMISTRY, 2002, 41 (03) : 752 - 759
  • [4] Bishop C. M., 1996, Neural networks for pattern recognition
  • [5] Sequence and structure-based prediction of eukaryotic protein phosphorylation sites
    Blom, N
    Gammeltoft, S
    Brunak, S
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1999, 294 (05) : 1351 - 1362
  • [6] Bossel H, 2002, CONSERV ECOL, V5
  • [7] Intrinsic disorder and protein function
    Dunker, AK
    Brown, CJ
    Lawson, JD
    Iakoucheva, LM
    Obradovic, Z
    [J]. BIOCHEMISTRY, 2002, 41 (21) : 6573 - 6582
  • [8] Coupling of folding and binding for unstructured proteins
    Dyson, HJ
    Wright, PE
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 2002, 12 (01) : 54 - 60
  • [9] Efron B., 1993, INTRO BOOTSTRAP, DOI 10.1007/978-1-4899-4541-9
  • [10] THE HYDROPHOBIC MOMENT DETECTS PERIODICITY IN PROTEIN HYDROPHOBICITY
    EISENBERG, D
    WEISS, RM
    TERWILLIGER, TC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (01): : 140 - 144