Source:http://linkedlifedata.com/resource/pubmed/id/12381310
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2002-10-16
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| pubmed:abstractText |
The number of intrinsically disordered proteins known to be involved in cell-signaling and regulation is growing rapidly. To test for a generalized involvement of intrinsic disorder in signaling and cancer, we applied a neural network predictor of natural disordered regions (PONDR VL-XT) to four protein datasets: human cancer-associated proteins (HCAP), signaling proteins (AfCS), eukaryotic proteins from SWISS-PROT (EU_SW) and non-homologous protein segments with well-defined (ordered) 3D structure (O_PDB_S25). PONDR VL-XT predicts >or=30 consecutive disordered residues for 79(+/-5)%, 66(+/-6)%, 47(+/-4)% and 13(+/-4)% of the proteins from HCAP, AfCS, EU_SW, and O_PDB_S25, respectively, indicating significantly more intrinsic disorder in cancer-associated and signaling proteins as compared to the two control sets. The disorder analysis was extended to 11 additional functionally diverse categories of human proteins from SWISS-PROT. The proteins involved in metabolism, biosynthesis, and degradation together with kinases, inhibitors, transport, G-protein coupled receptors, and membrane proteins are predicted to have at least twofold less disorder than regulatory, cancer-associated and cytoskeletal proteins. In contrast to 44.5% of the proteins from representative non-membrane categories, just 17.3% of the cancer-associated proteins had sequence alignments with structures in the Protein Data Bank covering at least 75% of their lengths. This relative lack of structural information correlated with the greater amount of predicted disorder in the HCAP dataset. A comparison of disorder predictions with the experimental structural data for a subset of the HCAP proteins indicated good agreement between prediction and observation. Our data suggest that intrinsically unstructured proteins play key roles in cell-signaling, regulation and cancer, where coupled folding and binding is a common mechanism.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0022-2836
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
25
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| pubmed:volume |
323
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
573-84
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12381310-Amino Acid Sequence,
pubmed-meshheading:12381310-Databases, Protein,
pubmed-meshheading:12381310-Drug Design,
pubmed-meshheading:12381310-Humans,
pubmed-meshheading:12381310-Molecular Sequence Data,
pubmed-meshheading:12381310-Neoplasm Proteins,
pubmed-meshheading:12381310-Neoplasms,
pubmed-meshheading:12381310-Protein Conformation,
pubmed-meshheading:12381310-Protein Structure, Tertiary,
pubmed-meshheading:12381310-Proteins,
pubmed-meshheading:12381310-Sequence Alignment,
pubmed-meshheading:12381310-Signal Transduction
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Intrinsic disorder in cell-signaling and cancer-associated proteins.
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| pubmed:affiliation |
Department of Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|