The Pfam Protein Families Database

Bateman, Alex; Birney, Ewan; Cerruti, Lorenzo; Durbin, Richard; Etwiller, Laurence; Eddy, Sean R.; Griffiths-Jones, Sam; Howe, Kevin; Marshall, Mhairi; Sonnhammer, Erik L. L.

doi:10.1093/nar/30.1.276

Cited by 4,075 publications

(1,771 citation statements)

References 18 publications

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“…INTERDOM predicts DD interactions from orthologous and other known PP interactions stored in databases. We used the Pfam database (22) to obtain the domains that each yeast protein contains when mapping DD interactions to PP interactions (see Supporting Text for the details of the estimation of P values for each of the five data sets).…”

Section: Resultsmentioning

confidence: 99%

A data integration methodology for systems biology: Experimental verification

Hwang

Smith²,

Leslie³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

122

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The integration of data from multiple global assays is essential to understanding dynamic spatiotemporal interactions within cells. In a companion paper, we reported a data integration methodology, designated Pointillist, that can handle multiple data types from technologies with different noise characteristics. Here we demonstrate its application to the integration of 18 data sets relating to galactose utilization in yeast. These data include global changes in mRNA and protein abundance, genome-wide protein-DNA interaction data, database information, and computational predictions of protein-DNA and protein-protein interactions. We divided the integration task to determine three network components: key system elements (genes and proteins), protein-protein interactions, and protein-DNA interactions. Results indicate that the reconstructed network efficiently focuses on and recapitulates the known biology of galactose utilization. It also provided new insights, some of which were verified experimentally. The methodology described here, addresses a critical need across all domains of molecular and cell biology, to effectively integrate large and disparate data sets.metabolism ͉ yeast ͉ molecular network model ͉ galactose S ystems biology aims to understand the dynamic behavior of molecular networks in the context of the global cell, organ and organism state by exploiting (i) high-throughput interrogation technologies; (ii) increasingly comprehensive databases of biomolecules and their interactions; and (iii) computational predictions of molecular function and interaction ( Fig. 1). Use of each of these sources of information has its own drawbacks (1). For example, many current global assays of mRNA and protein abundance͞state are systematically biased toward more abundant species and measure only the average content of many thousands of cells. Global assays are also inherently noisy and include significant numbers of false positives and false negatives. Databases tend to combine data from different cell types, different strains of an organism, and different experimental conditions. Moreover, well studied molecules and pathways are systematically overrepresented in databases. As a result, integration of database information with a particular set of experimental data can introduce systematic biases into the modelbuilding process. Likewise, computer predictions tend to be more accurate for members of well characterized molecular families. Therefore, there is a pressing need for data integration methodologies that effectively address both random noise and systematic bias in data.In a companion paper (2), we present a data integration methodology and its software implementation to address these challenges. To present the methodology clearly, we used only simulated data in that paper. Here, we present the application of our methodology (named Pointillist) to 18 types of biological data, which we integrate to arrive at a detailed and comprehensive picture of galactose utilization in yeast. The data we integrate include in...

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Section: Resultsmentioning

confidence: 99%

A data integration methodology for systems biology: Experimental verification

Hwang

Smith²,

Leslie³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

122

View full text Add to dashboard Cite

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“…The classification of DNA glycosylases into superfamilies, can be based on characteristic sequence motifs as defined in the Pfam database (Bateman et al, 2002). The two largest superfamilies are uracil DNA glycosylases (UDG) and helix -hairpin -helix -GPD glycosylases (HhH -GPD).…”

Section: Evolution Of Uracil-dna Glycosylasesmentioning

confidence: 99%

Uracil in DNA – occurrence, consequences and repair

2002

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“…The RCC1 motif derives its name from the RCC1 protein, a guanine nucleotide exchange factor for the Ran GTPase (20). RCC1 domains comprise ϳ50 amino acids that adopt a ␤-sheet conformation (21). In the case of the RCC1 protein, seven of these domains are tandemly arranged to comprise a seven-bladed propeller (41).…”

Section: Rcc1mentioning

confidence: 99%

“…RCC1 has been shown to function as a guanine nucleotide exchange factor (GEF) for the Ran family of GTPases (20). Although more than 90 proteins that contain one or more RCC1 repeats are present in data bases (21), only RCC1 itself has Ran GEF activity. Alsin also contains centrally located diffuse B-cell lymphoma (Dbl) homology (DH) and pleckstrin homology (PH) domains, a hallmark of guanine nucleotide exchange factors for the Rho GTPase family (22).…”

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confidence: 99%

Alsin Is a Rab5 and Rac1 Guanine Nucleotide Exchange Factor

Topp

Gray

Gerard

et al. 2004

Journal of Biological Chemistry

174

157

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ALS2 is the gene mutated in a recessive juvenile form of amyotrophic lateral sclerosis (ALS2). ALS2 encodes a large protein termed alsin, which contains a number of predicted cell signaling and protein trafficking sequence motifs. To gain insight into the overall function of alsin and to begin to evaluate its role in motor neuron maintenance, we examined the subcellular localization of alsin and the biochemical activities associated with its individual subdomains. We found that the Vps9p domain of alsin has Rab5 guanine nucleotide exchange activity. In addition, alsin interacted specifically with and acted as a guanine nucleotide exchange factor for Rac1. Immunofluorescence and fractionation experiments in both fibroblasts and neurons revealed that alsin is a cytosolic protein, with a significant portion associated with small, punctate membrane structures. Many of these membrane structures also contained Rab5 or Rac1. Upon overexpression of full-length alsin, the overexpressed material was largely cytosolic, indicating that the association with membrane structures could be saturated. We also found that alsin was present in membrane ruffles and lamellipodia. These data suggest that alsin is involved in membrane transport events, potentially linking endocytic processes and actin cytoskeleton remodeling.Amyotrophic lateral sclerosis (ALS) 1 is a heterogeneous neurological disorder characterized by progressive degeneration of motor neurons, usually causing death as a result of respiratory paralysis (1, 2). Although mostly sporadic in nature, a genetic link has been established in 5-10% of ALS cases (3). Chromosomal mapping studies have identified six independent loci associated with the familial forms of ALS (Refs. 4 -10; reviewed in Refs. 11 and 12). Molecular genetic analysis identified two genes that, when mutated, lead to ALS. The first discovered was the gene coding for Cu-Zn superoxide dismutase 1 (SOD1) (10). Initially, mutations in SOD1 were thought to result in defective free radical scavenger activity. However, it is now generally accepted that the alterations in SOD1 that lead to ALS are the result of an unknown, but toxic gain-of-function. The second gene identified is mutated in a juvenile form of ALS, ALS2 (13,14). Mutations in this gene lead to a rare recessive form of ALS that presents early in life and progresses much more slowly than the classical form (6, 15). Two small deletions in ALS2 were originally associated with the disease (13,14). Each is expected to severely truncate the predicted protein product of ALS2. In addition, mutations in ALS2 have recently been associated with two other neurodegenerative disorders, juvenile-onset primary lateral sclerosis (14) and infantile-onset hereditary spastic paralegia (16 -18). Like the original mutations identified, these mutations are predicted to generate prematurely truncated forms of the protein product.The protein encoded by ALS2, alsin, is predicted to contain numerous domains implicating roles in cell signaling, membrane localization, and protein...

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The Pfam Protein Families Database

Cited by 4,075 publications

References 18 publications

A data integration methodology for systems biology: Experimental verification

A data integration methodology for systems biology: Experimental verification

Uracil in DNA – occurrence, consequences and repair

Alsin Is a Rab5 and Rac1 Guanine Nucleotide Exchange Factor

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