Intermediate sequences increase the detection of homology between sequences

Park, Jong; Teichmann, Sarah A.; Hubbard, Tim; Chothia, Cyrus

doi:10.1006/jmbi.1997.1288

Cited by 207 publications

(167 citation statements)

References 17 publications

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“…Ras-related sequences in Swissprot belonging to main subfamilies (Ras, Rho, and Rab) were exhaustively collected using ISS-BLAST (Intermediate Sequence Searches) (Park et al, 1997). Multiple sequences alignment were built with CLUSTALW using BLOSUM62 matrix (Henikoff and Henikoff, 1992) for Rhes and the other Ras sequence subfamilies.…”

Section: Sequence Analysismentioning

confidence: 99%

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors

et al. 2004

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The Ras homolog enriched in striatum, Rhes, is the product of a thyroid hormone-regulated gene during brain development. Rhes and the dexamethasone-induced Dexras1 define a novel distinct subfamily of proteins within the Ras family, characterized by an extended variable domain in the carboxyl terminal region. We have carried this study because there is a complete lack of knowledge on Rhes signaling. We show that in PC12 cells, Rhes is targeted to the plasma membrane by farnesylation. We demonstrate that about 30% of the native Rhes protein is bound to GTP and this proportion is unaltered by typical Ras family nucleotide exchange factors. However, Rhes is not transforming in murine fibroblasts. We have also examined the role of Rhes in cell signaling. Rhes does not stimulate the ERK pathway. By contrast, it binds to and activates PI3K. On the other hand, we demonstrate that Rhes impairs the activation of the cAMP/PKA pathway by thyroid-stimulating hormone, and by an activated b2 adrenergic receptor by a mechanism that suggests uncoupling of the receptor to its cognate heterotrimeric complex. Overall, our results provide the initial insights into the role in signal transduction of this novel Ras family member.

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Section: Sequence Analysismentioning

confidence: 99%

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors

et al. 2004

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“…®rst carry out a database search against the sequence of interest and then carry out database searches with each sequence returned from the ®rst search. Calibration against PDB40D showed that using the same algorithm (FASTA) this approach increases the coverage by~70% when applying the 1% error-rate threshold (Park et al, 1997). Work to evaluate sequence search methods relying on multiple sequence alignments such as Hidden Markov Models (Eddy, 1996;Krogh et al, 1994) and the recently developed iterative version of BLAST2 (Altschul et al, 1997) (referred to as psi-BLAST) have shown signi®cantly better performance by the same criteria (Park et al, unpublished results; Brenner et al, in preparation).…”

Section: Coveragementioning

confidence: 99%

SCOP, Structural Classification of Proteins Database: Applications to Evaluation of the Effectiveness of Sequence Alignment Methods and Statistics of Protein Structural Data

Hubbard

Ailey

Brenner

et al. 1998

Acta Crystallogr D Biol Crystallogr

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The Structural Classi®cation of Proteins (SCOP) database provides a detailed and comprehensive description of the relationships of all known protein structures. The classi®cation is on hierarchical levels: the ®rst two levels, family and superfamily, describe near and far evolutionary relationships; the third, fold, describes geometrical relationships. The distinction between evolutionary relationships and those that arise from the physics and chemistry of proteins is a feature that is unique to this database, so far. The database can be used as a source of data to calibrate sequence search algorithms and for the generation of population statistics on protein structures. The database and its associated ®les are freely accessible from a number of WWW sites mirrored from URL http://scop.mrc-lmb. cam.ac.uk/scop/.

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“…Sequence Analysis of the Conserved N-terminal Region of the SBDS Family-The alignment of the orthologues of human SBDS was used to search for distant protein families via intermediate searches (26) using global hidden Markov model profiles (using hmmsearch of HMMer; hmmer.wustl.edu/) (27). To improve the profile quality we followed two approaches: first, BLAST searches against unfinished genomes (28), and secondly, additional searches against EST databases (29), using NAIL to view and analyze the HMMer results (30).…”

mentioning

confidence: 99%

The Shwachman-Bodian-Diamond Syndrome Protein Family Is Involved in RNA Metabolism

Savchenko¹,

Krogan

Cort

et al. 2005

Journal of Biological Chemistry

102

104

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A combination of structural, biochemical, and genetic studies in model organisms was used to infer a cellular role for the human protein (SBDS) responsible for Shwachman-Bodian-Diamond syndrome. The crystal structure of the SBDS homologue in Archaeoglobus fulgidus, AF0491, revealed a three domain protein. The N-terminal domain, which harbors the majority of diseaselinked mutations, has a novel three-dimensional fold. The central domain has the common winged helix-turn-helix motif, and the C-terminal domain shares structural homology with known RNA-binding domains. Proteomic analysis of the SBDS sequence homologue in Saccharomyces cerevisiae, YLR022C, revealed an association with over 20 proteins involved in ribosome biosynthesis. NMR structural genomics revealed another yeast protein, YHR087W, to be a structural homologue of the AF0491 N-terminal domain. Sequence analysis confirmed them as distant sequence homologues, therefore related by divergent evolution. Synthetic genetic array analysis of YHR087W revealed genetic interactions with proteins involved in RNA and rRNA processing including Mdm20/ Nat3, Nsr1, and Npl3. Our observations, taken together with previous reports, support the conclusion that SBDS and its homologues play a role in RNA metabolism.

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Intermediate sequences increase the detection of homology between sequences

Cited by 207 publications

References 17 publications

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors

SCOP, Structural Classification of Proteins Database: Applications to Evaluation of the Effectiveness of Sequence Alignment Methods and Statistics of Protein Structural Data

The Shwachman-Bodian-Diamond Syndrome Protein Family Is Involved in RNA Metabolism

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