Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (346K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (135)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Iakoucheva, L. M.
Right arrow Articles by Dunker, A. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iakoucheva, L. M.
Right arrow Articles by Dunker, A. K.
Related Collections
Right arrow Computational methods
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 11 February 2004

Nucleic Acids Research, 2004, Vol. 32, No. 3 1037-1049
© 2004 Oxford University Press

The importance of intrinsic disorder for protein phosphorylation

Lilia M. Iakoucheva, Predrag Radivojac1, Celeste J. Brown, Timothy R. O’Connor, Jason G. Sikes, Zoran Obradovic1 and A. Keith Dunker*

School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA and 1 Center for Information Science and Technology, Temple University, Philadelphia, PA 19122, USA

*To whom correspondence should be addressed at: Biochemistry and Molecular Biology, 635 Barnhill Drive, MS 4023, Indianapolis, IN 46202-5122, USA. Tel: +1 317 278 9650; Fax: +1 317 274 4686; Email: kedunker{at}iupui.edu
Present addresses:
Lilia M. Iakoucheva, The Rockefeller University, Laboratory of Statistical Genetics, New York, NY 10021, USA
Celeste J. Brown, IBEST, University of Idaho, Moscow, ID 83844-1010, USA
A. Keith Dunker, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors

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, http://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 non-phosphorylation 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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
C. M. Lightcap, S. Sun, J. D. Lear, U. Rodeck, T. Polenova, and J. C. Williams
Biochemical and Structural Characterization of the Pak1-LC8 Interaction
J. Biol. Chem., October 3, 2008; 283(40): 27314 - 27324.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
Y. Xue, J. Ren, X. Gao, C. Jin, L. Wen, and X. Yao
GPS 2.0, a Tool to Predict Kinase-specific Phosphorylation Sites in Hierarchy
Mol. Cell. Proteomics, September 1, 2008; 7(9): 1598 - 1608.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
P. Radivojac, P. H. Baenziger, M. G. Kann, M. E. Mort, M. W. Hahn, and S. D. Mooney
Gain and loss of phosphorylation sites in human cancer
Bioinformatics, August 15, 2008; 24(16): i241 - i247.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Rotem, C. Katz, H. Benyamini, M. Lebendiker, D. Veprintsev, S. Rudiger, T. Danieli, and A. Friedler
The Structure and Interactions of the Proline-rich Domain of ASPP2
J. Biol. Chem., July 4, 2008; 283(27): 18990 - 18999.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
M. O. Collins, L. Yu, I. Campuzano, S. G. N. Grant, and J. S. Choudhary
Phosphoproteomic Analysis of the Mouse Brain Cytosol Reveals a Predominance of Protein Phosphorylation in Regions of Intrinsic Sequence Disorder
Mol. Cell. Proteomics, July 1, 2008; 7(7): 1331 - 1348.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
A. Hafren and K. Makinen
Purification of viral genome-linked protein VPg from potato virus A-infected plants reveals several post-translationally modified forms of the protein
J. Gen. Virol., June 1, 2008; 89(6): 1509 - 1518.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Wang, M. K. Choi, T. Ban, H. Yanai, H. Negishi, Y. Lu, T. Tamura, A. Takaoka, K. Nishikura, and T. Taniguchi
Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules
PNAS, April 8, 2008; 105(14): 5477 - 5482.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Wan, S. Kang, C. Tang, J. Yan, Y. Ren, J. Liu, X. Gao, A. Banerjee, L. B. M. Ellis, and T. Li
Meta-prediction of phosphorylation sites with weighted voting and restricted grid search parameter selection
Nucleic Acids Res., March 27, 2008; 36(4): e22 - e22.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
K. S. Kocherlakota, J.-m. Wu, J. McDermott, and S. M. Abmayr
Analysis of the Cell Adhesion Molecule Sticks-and-Stones Reveals Multiple Redundant Functional Domains, Protein-Interaction Motifs and Phosphorylated Tyrosines That Direct Myoblast Fusion in Drosophila melanogaster
Genetics, March 1, 2008; 178(3): 1371 - 1383.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
W. Gong, D. Zhou, Y. Ren, Y. Wang, Z. Zuo, Y. Shen, F. Xiao, Q. Zhu, A. Hong, X. Zhou, et al.
PepCyber:P~PEP: a database of human protein protein interactions mediated by phosphoprotein-binding domains
Nucleic Acids Res., January 11, 2008; 36(suppl_1): D679 - D683.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
L. M. Espinoza-Fonseca, D. Kast, and D. D. Thomas
Molecular Dynamics Simulations Reveal a Disorder-to-Order Transition on Phosphorylation of Smooth Muscle Myosin
Biophys. J., September 15, 2007; 93(6): 2083 - 2090.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
Y.-R. Tang, Y.-Z. Chen, C. A. Canchaya, and Z. Zhang
GANNPhos: a new phosphorylation site predictor based on a genetic algorithm integrated neural network
Protein Eng. Des. Sel., August 1, 2007; 20(8): 405 - 412.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y.-H. Wong, T.-Y. Lee, H.-K. Liang, C.-M. Huang, T.-Y. Wang, Y.-H. Yang, C.-H. Chu, H.-D. Huang, M.-T. Ko, and J.-K. Hwang
KinasePhos 2.0: a web server for identifying protein kinase-specific phosphorylation sites based on sequences and coupling patterns
Nucleic Acids Res., July 13, 2007; 35(suppl_2): W588 - W594.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Ishida and K. Kinoshita
PrDOS: prediction of disordered protein regions from amino acid sequence
Nucleic Acids Res., July 13, 2007; 35(suppl_2): W460 - W464.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Borg, T. Mittag, T. Pawson, M. Tyers, J. D. Forman-Kay, and H. S. Chan
Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity
PNAS, June 5, 2007; 104(23): 9650 - 9655.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
M. Fuxreiter, P. Tompa, and I. Simon
Local structural disorder imparts plasticity on linear motifs
Bioinformatics, April 15, 2007; 23(8): 950 - 956.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
C. R. Ingrell, M. L. Miller, O. N. Jensen, and N. Blom
NetPhosYeast: prediction of protein phosphorylation sites in yeast
Bioinformatics, April 1, 2007; 23(7): 895 - 897.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
P. Radivojac, L. M. Iakoucheva, C. J. Oldfield, Z. Obradovic, V. N. Uversky, and A. K. Dunker
Intrinsic Disorder and Functional Proteomics
Biophys. J., March 1, 2007; 92(5): 1439 - 1456.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
E. Youn, B. Peters, P. Radivojac, and S. D. Mooney
Evaluation of features for catalytic residue prediction in novel folds
Protein Sci., February 1, 2007; 16(2): 216 - 226.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Zanzoni, G. Ausiello, A. Via, P. F. Gherardini, and M. Helmer-Citterich
Phospho3D: a database of three-dimensional structures of protein phosphorylation sites
Nucleic Acids Res., January 12, 2007; 35(suppl_1): D229 - D231.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
N. Salamat-Miller, J. Fang, C. W. Seidel, A. M. Smalter, Y. Assenov, M. Albrecht, and C. R. Middaugh
A Network-based Analysis of Polyanion-binding Proteins Utilizing Yeast Protein Arrays
Mol. Cell. Proteomics, December 1, 2006; 5(12): 2263 - 2278.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Honnappa, W. Jahnke, J. Seelig, and M. O. Steinmetz
Control of Intrinsically Disordered Stathmin by Multisite Phosphorylation
J. Biol. Chem., June 9, 2006; 281(23): 16078 - 16083.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C. Haynes and L. M. Iakoucheva
Serine/arginine-rich splicing factors belong to a class of intrinsically disordered proteins
Nucleic Acids Res., January 10, 2006; 34(1): 305 - 312.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T.-Y. Lee, H.-D. Huang, J.-H. Hung, H.-Y. Huang, Y.-S. Yang, and T.-H. Wang
dbPTM: an information repository of protein post-translational modification
Nucleic Acids Res., January 1, 2006; 34(suppl_1): D622 - D627.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S.-W. Chi, S.-H. Lee, D.-H. Kim, M.-J. Ahn, J.-S. Kim, J.-Y. Woo, T. Torizawa, M. Kainosho, and K.-H. Han
Structural Details on mdm2-p53 Interaction
J. Biol. Chem., November 18, 2005; 280(46): 38795 - 38802.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. N. Khan and P. N. Lewis
Unstructured Conformations Are a Substrate Requirement for the Sir2 Family of NAD-dependent Protein Deacetylases
J. Biol. Chem., October 28, 2005; 280(43): 36073 - 36078.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Roque, I. Iloro, I. Ponte, J. L. R. Arrondo, and P. Suau
DNA-induced Secondary Structure of the Carboxyl-terminal Domain of Histone H1
J. Biol. Chem., September 16, 2005; 280(37): 32141 - 32147.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y. Xue, F. Zhou, M. Zhu, K. Ahmed, G. Chen, and X. Yao
GPS: a comprehensive www server for phosphorylation sites prediction
Nucleic Acids Res., July 1, 2005; 33(suppl_2): W184 - W187.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
H.-D. Huang, T.-Y. Lee, S.-W. Tzeng, and J.-T. Horng
KinasePhos: a web tool for identifying protein kinase-specific phosphorylation sites
Nucleic Acids Res., July 1, 2005; 33(suppl_2): W226 - W229.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
L. S. Jones, B. Yazzie, and C. R. Middaugh
Polyanions and the Proteome
Mol. Cell. Proteomics, August 1, 2004; 3(8): 746 - 769.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Li, R. M. Wynn, M. Machius, J. L. Chuang, S. Karthikeyan, D. R. Tomchick, and D. T. Chuang
Cross-talk between Thiamin Diphosphate Binding and Phosphorylation Loop Conformation in Human Branched-chain {alpha}-Keto Acid Decarboxylase/Dehydrogenase
J. Biol. Chem., July 30, 2004; 279(31): 32968 - 32978.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.