Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods

Park, Jong; Karplus, Kevin; Barrett, Christian; Hughey, Richard; Haussler, David; Hubbard, Tim; Chothia, Cyrus

doi:10.1006/jmbi.1998.2221

Cited by 486 publications

(400 citation statements)

References 26 publications

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“…We also identified this domain in a cytoplasmic protein of unknown function, NDP52 (34). All EXPECT scores are well below the significance threshold of 1 ϫ 10 Ϫ6 as described by Park et al (35). A sequence alignment of all domains revealed that this novel domain is characterized by the highly conserved motif DWXGX 3 VGX 6 YX 4 W and a second motif, GX 3 PF (Fig.…”

Section: Skip Translocates To the Plasma Membrane Of Egf-orsupporting

confidence: 64%

Identification of a Novel Domain in Two Mammalian Inositol-polyphosphate 5-Phosphatases That Mediates Membrane Ruffle Localization

Gurung

Tan

Ooms

et al. 2003

Journal of Biological Chemistry

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SKIP (skeletal muscle and kidney enriched inositol phosphatase) is a recently identified phosphatidylinositol 3,4,5-trisphosphate-and phosphatidylinositol 4,5-bisphosphate-specific 5-phosphatase. In this study, we investigated the intracellular localization of SKIP. Indirect immunofluorescence and subcellular fractionation showed that, in serum-starved cells, both endogenous and recombinant SKIP colocalized with markers of the endoplasmic reticulum (ER). Following epidermal growth factor (EGF) stimulation, SKIP transiently translocated to plasma membrane ruffles and colocalized with submembranous actin. Data base searching demonstrated a novel 128-amino acid domain in the C terminus of SKIP, designated SKICH for SKIP carboxyl homology, which is also found in the 107-kDa 5-phosphatase PIPP and in members of the TRAF6-binding protein family. Recombinant SKIP lacking the SKICH domain localized to the ER, but did not translocate to membrane ruffles following EGF stimulation. The SKIP SKICH domain showed perinuclear localization and mediated EGF-stimulated plasma membrane ruffle localization. The SKICH domain of the 5-phosphatase PIPP also mediated plasma membrane ruffle localization. Mutational analysis identified the core sequence within the SKICH domain that mediated constitutive membrane association and C-terminal sequences unique to SKIP that contributed to ER localization. Collectively, these studies demonstrate a novel membrane-targeting domain that serves to recruit SKIP and PIPP to membrane ruffles.Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) 1 serves as a precursor to two major signaling pathways. This central phosphoinositide is phosphorylated by phosphoinositide 3-kinase, forming PtdIns(3,4,5)P 3 , which transiently accumulates at the plasma membrane of growth factor-activated cells and is subsequently rapidly metabolized by PtdIns(3,4,5)P 3 5-or 3-phosphate-specific lipid phosphatases. PtdIns(3,4,5)P 3 recruits various effector proteins that contain PH domains, such as the serine/threonine kinases Akt and PDK1 (1), and Rho, Rac, and ADP-ribosylation factor guanine nucleotide exchange factors, including P-Rex1 (2) and SWAP-70 (3), which in turn regulate many signaling pathways, including inhibition of cell death, cell cycle progression, actin polymerization, membrane ruffling, cell migration, and secretion (4 -7). In addition, PtdIns(4,5)P 2 is hydrolyzed by phospholipase C to produce inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) and diacylglycerol, which mobilize intracellular calcium and activate protein kinase C, respectively. PtdIns(4,5)P 2 itself regulates the activity of actin-binding proteins by suppressing the function of vinculin, cofilin, gelsolin, and profilin and by activating the actin-gelatinizing activity of ␣-actinin (8).The inositol-polyphosphate 5-phosphatases (referred to as 5-phosphatases) are a large family of signal-modifying enzymes that hydrolyze the 5-phosphate from the inositol ring of both inositol phosphates, such as Ins(1,4,5)P 3 and Ins(1,3,4,5)P 4 , and/or PtdIns-...

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Section: Skip Translocates To the Plasma Membrane Of Egf-orsupporting

confidence: 64%

Identification of a Novel Domain in Two Mammalian Inositol-polyphosphate 5-Phosphatases That Mediates Membrane Ruffle Localization

Gurung

Tan

Ooms

et al. 2003

Journal of Biological Chemistry

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“…For example, the relative performance of SVM-Fisher and SAM agrees with the results given in Jaakkola et al, 10 as does the relative performance of SAM and PSI-BLAST with the results given in Park et al 28 and the relative performance of SVM-I-sites and SVM-pairwise given in Hou et al 16 One surprise is the magnitude of the difference between SVM-pairwise and the 2 methods, SVM-Fisher and SAM, that directly or indirectly utilize SAM-T99 model. It is reported in Liao and Noble 11 that SVM-pairwise significantly outperforms these 2 methods, which is not the case in this work.…”

Section: Resultssupporting

confidence: 88%

Remote homolog detection using local sequence–structure correlations

et al. 2004

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Remote homology detection refers to the detection of structural homology in proteins when there is little or no sequence similarity. In this article, we present a remote homolog detection method called SVM-HMMSTR that overcomes the reliance on detectable sequence similarity by transforming the sequences into strings of hidden Markov states that represent local folding motif patterns. These state strings are transformed into fixeddimension feature vectors for input to a support vector machine. Two sets of features are defined: an order-independent feature set that captures the amino acid and local structure composition; and an order-dependent feature set that captures the sequential ordering of the local structures. Tests using the Structural Classification of Proteins (SCOP) 1.53 data set show that the SVM-HMMSTR gives a significant improvement over several current methods. Proteins 2004;57:518 -530.

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“…Profile/HMM/PSSM methods are more sensitive than single-sequence comparison methods because they summarize the evolutionary history of a family, identifying more and less conserved positions within the protein [39]. Recently, profile/HMM/PSSM-based methods have been extended to provide profile-profile based comparisons [19•,40-43].…”

Section: Progress In Sequence Similarity Searchingmentioning

confidence: 99%

The limits of protein sequence comparison?

Pearson

Sierk

2005

Current Opinion in Structural Biology

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Modern sequence alignment algorithms are used routinely to identify homologous proteins, proteins that share a common ancestor. Homologous proteins always share similar structures and often have similar functions. Over the past 20 years, sequence comparison has become both more sensitive, largely because of profile-based methods, and more reliable, because of more accurate statistical estimates. As sequence and structure databases become larger, and comparison methods become more powerful, reliable statistical estimates will become even more important for distinguishing similarities that are due to homology from those that are due to analogy (convergence). The newest sequence alignment methods are more sensitive than older methods, but more accurate statistical estimates are needed for their full power to be realized.

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Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods

Cited by 486 publications

References 26 publications

Identification of a Novel Domain in Two Mammalian Inositol-polyphosphate 5-Phosphatases That Mediates Membrane Ruffle Localization

Identification of a Novel Domain in Two Mammalian Inositol-polyphosphate 5-Phosphatases That Mediates Membrane Ruffle Localization

Remote homolog detection using local sequence–structure correlations

The limits of protein sequence comparison?

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