Rate4Site: an algorithmic tool for the identification of functional regions 
in proteins by surface mapping of evolutionary determinants within their 
homologues

Pupko, Tal; Bell, Rachel E.; Mayrose, Itay; Glaser, Fabian; Ben‐Tal, Nir

doi:10.1093/bioinformatics/18.suppl_1.s71

Cited by 594 publications

(540 citation statements)

References 27 publications

Supporting

Mentioning

535

Contrasting

Unclassified

Order By: Relevance

“…The degree of conservation of the polymorphic residues was analysed using ConSeq (http://conseq.tau.ac.il), the sequence only variant of Rate4Site, an algorithmic tool for the identification of functional regions in proteins. 32 on the Cx26 protein can be tested if cochlear tissue harbouring this mutation is available for study. Our results thus indicate that the Cx26 mutations associated with hearing loss affects gap junction activity by multiple mechanisms but lead to an almost identical clinical phenotype of severe-to-profound hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

et al. 2008

View full text Add to dashboard Cite

In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (À23G4T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1 þ 1G4A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

et al. 2008

View full text Add to dashboard Cite

show abstract

“…(D) P23 interacts with HSP90 at three points: the middle domain (shown in green) and the NTD (light green) of a HSP90 monomer as well as the NTD of the other HSP90 monomer (light pink) (Ali et al, 2006). (E) and (F) Conserved amino acid residues in SGT1 (E) and P23 (F) calculated using the Rate4site algorithm (Pupko et al, 2002). Colors from red to white indicate the most conserved to the most variable positions.…”

Section: Cs and Sgs Domains Are Required For Rx Resistancementioning

confidence: 99%

Structural and Functional Analysis of SGT1 Reveals That Its Interaction with HSP90 Is Required for the Accumulation of Rx, an R Protein Involved in Plant Immunity

et al. 2007

View full text Add to dashboard Cite

SGT1 (for suppressor of G2 allele of skp1) and RAR1 (for required for Mla12 resistance) are highly conserved eukaryotic proteins that interact with the molecular chaperone HSP90 (for heat shock protein90). In plants, SGT1, RAR1, and HSP90 are essential for disease resistance triggered by a number of resistance (R) proteins. Here, we present structural and functional characterization of plant SGT1 proteins. Random mutagenesis of Arabidopsis thaliana SGT1b revealed that its CS (for CHORD-SGT1) and SGS (for SGT1 specific) domains are essential for disease resistance. NMR-based interaction surface mapping and mutational analyses of the CS domain showed that the CHORD II domain of RAR1 and the N-terminal domain of HSP90 interact with opposite sides of the CS domain. Functional analysis of the CS mutations indicated that the interaction between SGT1 and HSP90 is required for the accumulation of Rx, a potato (Solanum tuberosum) R protein.Biochemical reconstitution experiments suggest that RAR1 may function to enhance the SGT1-HSP90 interaction by promoting ternary complex formation.

show abstract

“…The 'Sponge' and 'Density' parameters are calculated using the double cubic lattice method (19) in combination with public library procedures such as those of the BALL's library (Biochemical Algorithms Libraryhttp://voyager.bioinf.uni-sb.de/OK/BALL) and our own code (details to be described elsewhere). In addition, we used the Rate4Site (20) software to calculate the 'Evolutionary Pressure' parameter shown within the J PD Conservation row. Pockets are calculated using the 'pocket' program designed by Patrice Koehl (http://csb.stanford.edu/koehl/ ProShape/) and adapted by us to our needs.…”

Section: Java Protein Dossier Structural/functional Parametersmentioning

confidence: 99%

JavaProtein Dossier: a novel web-based data visualization tool for comprehensive analysis of protein structure

Neshich¹,

Rocchia²,

Mancini³

et al. 2004

Nucleic Acids Research

View full text Add to dashboard Cite

JavaProtein Dossier ( J PD) is a new concept, database and visualization tool providing one of the largest collections of the physicochemical parameters describing proteins' structure, stability, function and interaction with other macromolecules. By collecting as many descriptors/parameters as possible within a single database, we can achieve a better use of the available data and information. Furthermore, data grouping allows us to generate different parameters with the potential to provide new insights into the sequence-structure-function relationship. In J PD, residue selection can be performed according to multiple criteria. J PD can simultaneously display and analyze all the physicochemical parameters of any pair of structures, using precalculated structural alignments, allowing direct parameter comparison at corresponding amino acid positions among homologous structures. In order to focus on the physicochemical (and consequently pharmacological) profile of proteins, visualization tools (showing the structure and structural parameters) also had to be optimized. Our response to this challenge was the use of Java technology with its exceptional level of interactivity. J PD is freely accessible (within the Gold Sting Suite) at

show abstract

Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues

Cited by 594 publications

References 27 publications

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

Structural and Functional Analysis of SGT1 Reveals That Its Interaction with HSP90 Is Required for the Accumulation of Rx, an R Protein Involved in Plant Immunity

JavaProtein Dossier: a novel web-based data visualization tool for comprehensive analysis of protein structure

Contact Info

Product

Resources

About