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58-591: [REDACTED] Look up eya in Wiktionary, the free dictionary. EYA may refer to: EYA1 gene and protein EYA2 gene and protein EYA4 gene and protein Eyak language , by ISO 639 code Eya Laure , Filipina volleyball player Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with
116-461: A transcriptional activator . Four transcript variants encoding three distinct isoforms have been identified for this gene. EYA1 has been shown to interact with SIX1 . This article on a gene on human chromosome 8 is a stub . You can help Misplaced Pages by expanding it . Protein-protein interaction Protein–protein interactions ( PPIs ) are physical contacts of high specificity established between two or more protein molecules as
174-454: A computational vector space that mimics protein fold space and includes all simultaneously contacted residue sets, which can be used to analyze protein structure-function relation and evolution. Large scale identification of PPIs generated hundreds of thousands of interactions, which were collected together in specialized biological databases that are continuously updated in order to provide complete interactomes . The first of these databases
232-1130: A general mechanism for homo-oligomer (multimer) formation. Hundreds of protein oligomers were identified that assemble in human cells by such an interaction. The most prevalent form of interaction is between the N-terminal regions of the interacting proteins. Dimer formation appears to be able to occur independently of dedicated assembly machines. The intermolecular forces likely responsible for self-recognition and multimer formation were discussed by Jehle. Diverse techniques to identify PPIs have been emerging along with technology progression. These include co-immunoprecipitation, protein microarrays , analytical ultracentrifugation , light scattering , fluorescence spectroscopy , luminescence-based mammalian interactome mapping (LUMIER), resonance-energy transfer systems, mammalian protein–protein interaction trap, electro-switchable biosurfaces , protein–fragment complementation assay , as well as real-time label-free measurements by surface plasmon resonance , and calorimetry . The experimental detection and characterization of PPIs
290-627: A higher than normal false positive rate. An empirical framework must be implemented to control for these false positives. Limitations in lower coverage of membrane proteins have been overcoming by the emergence of yeast two-hybrid variants, such as the membrane yeast two-hybrid (MYTH) and the split-ubiquitin system, which are not limited to interactions that occur in the nucleus; and, the bacterial two-hybrid system, performed in bacteria; Affinity purification coupled to mass spectrometry mostly detects stable interactions and thus better indicates functional in vivo PPIs. This method starts by purification of
348-504: A manually produced molecular interaction map is the Kurt Kohn's 1999 map of cell cycle control. Drawing on Kohn's map, Schwikowski et al. in 2000 published a paper on PPIs in yeast, linking 1,548 interacting proteins determined by two-hybrid screening. They used a layered graph drawing method to find an initial placement of the nodes and then improved the layout using a force-based algorithm. Bioinformatic tools have been developed to simplify
406-474: A multitude of methods to detect them. Each of the approaches has its own strengths and weaknesses, especially with regard to the sensitivity and specificity of the method. The most conventional and widely used high-throughput methods are yeast two-hybrid screening and affinity purification coupled to mass spectrometry . This system was firstly described in 1989 by Fields and Song using Saccharomyces cerevisiae as biological model. Yeast two hybrid allows
464-461: A positive set (known interacting protein pairs) and a negative set (non-interacting protein pairs) is needed for the development of a computational prediction model. Prediction models using machine learning techniques can be broadly classified into two main groups: supervised and unsupervised, based on the labeling of input variables according to the expected outcome. In 2005, integral membrane proteins of Saccharomyces cerevisiae were analyzed using
522-423: A problem when studying proteins that contain mammalian-specific post-translational modifications. The number of PPIs identified is usually low because of a high false negative rate; and, understates membrane proteins , for example. In initial studies that utilized Y2H, proper controls for false positives (e.g. when DB-X activates the reporter gene without the presence of AD-Y) were frequently not done, leading to
580-553: A result of biochemical events steered by interactions that include electrostatic forces , hydrogen bonding and the hydrophobic effect . Many are physical contacts with molecular associations between chains that occur in a cell or in a living organism in a specific biomolecular context. Proteins rarely act alone as their functions tend to be regulated. Many molecular processes within a cell are carried out by molecular machines that are built from numerous protein components organized by their PPIs. These physiological interactions make up
638-736: A set of proteins that are highly connected to each other in PPI network. It is almost similar problem as community detection in social networks . There are some methods such as Jactive modules and MoBaS. Jactive modules integrate PPI network and gene expression data where as MoBaS integrate PPI network and Genome Wide association Studies . protein–protein relationships are often the result of multiple types of interactions or are deduced from different approaches, including co-localization, direct interaction, suppressive genetic interaction, additive genetic interaction, physical association, and other associations. Protein–protein interactions often result in one of
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#1733092513287696-494: A single protein in another genome. Therefore, we can predict if two proteins may be interacting by determining if they each have non-overlapping sequence similarity to a region of a single protein sequence in another genome. The Conserved Neighborhood method is based on the hypothesis that if genes encoding two proteins are neighbors on a chromosome in many genomes, then they are likely functionally related (and possibly physically interacting). The Phylogenetic Profile method
754-526: A supervised technique, was found to be the most-effective machine learning method for protein interaction prediction. Such methods have been applied for discovering protein interactions on human interactome, specifically the interactome of Membrane proteins and the interactome of Schizophrenia-associated proteins. As of 2020, a model using residue cluster classes (RCCs), constructed from the 3DID and Negatome databases, resulted in 96-99% correctly classified instances of protein–protein interactions. RCCs are
812-482: A tyrosine residue into a phenylalanine, have shown that water mediated interactions can contribute to the energy of interaction. Thus, water molecules may facilitate the interactions and cross-recognitions between proteins. The molecular structures of many protein complexes have been unlocked by the technique of X-ray crystallography . The first structure to be solved by this method was that of sperm whale myoglobin by Sir John Cowdery Kendrew . In this technique
870-415: A variety of organisms including the fungi Neurospora crassa , Saccharomyces cerevisiae and Schizosaccharomyces pombe ; the bacterium Salmonella typhimurium ; the virus bacteriophage T4 , an RNA virus and humans. In such studies, numerous mutations defective in the same gene were often isolated and mapped in a linear order on the basis of recombination frequencies to form a genetic map of
928-515: Is a protein that in humans is encoded by the EYA1 gene . This gene encodes a member of the eyes absent (EYA) subfamily of proteins . The encoded protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations of this gene have been associated with branchiootorenal dysplasia syndrome , branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies. A similar protein in mice can act as
986-418: Is based on the hypothesis that if two or more proteins are concurrently present or absent across several genomes, then they are likely functionally related. Therefore, potentially interacting proteins can be identified by determining the presence or absence of genes across many genomes and selecting those genes which are always present or absent together. Publicly available information from biomedical documents
1044-450: Is based on the study of magnetic properties of atomic nuclei, thus determining physical and chemical properties of the correspondent atoms or the molecules. Nuclear magnetic resonance is advantageous for characterizing weak PPIs. Some proteins have specific structural domains or sequence motifs that provide binding to other proteins. Here are some examples of such domains: The study of the molecular structure can give fine details about
1102-818: Is extracted. There are also studies using phylogenetic profiling , basing their functionalities on the theory that proteins involved in common pathways co-evolve in a correlated fashion across species. Some more complex text mining methodologies use advanced Natural Language Processing (NLP) techniques and build knowledge networks (for example, considering gene names as nodes and verbs as edges). Other developments involve kernel methods to predict protein interactions. Many computational methods have been suggested and reviewed for predicting protein–protein interactions. Prediction approaches can be grouped into categories based on predictive evidence: protein sequence, comparative genomics , protein domains, protein tertiary structure, and interaction network topology. The construction of
1160-516: Is guided by the establishment of non-covalent interactions in the quaternary structure of the protein. Disruption of homo-oligomers in order to return to the initial individual monomers often requires denaturation of the complex. Several enzymes , carrier proteins , scaffolding proteins, and transcriptional regulatory factors carry out their functions as homo-oligomers. Distinct protein subunits interact in hetero-oligomers, which are essential to control several cellular functions. The importance of
1218-535: Is important to note that some of the interactions in the STRING database are only predicted by computational methods such as Genomic Context and not experimentally verified. Information found in PPIs databases supports the construction of interaction networks. Although the PPI network of a given query protein can be represented in textbooks, diagrams of whole cell PPIs are frankly complex and difficult to generate. One example of
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#17330925132871276-463: Is labor-intensive and time-consuming. However, many PPIs can be also predicted computationally, usually using experimental data as a starting point. However, methods have also been developed that allow the prediction of PPI de novo, that is without prior evidence for these interactions. The Rosetta Stone or Domain Fusion method is based on the hypothesis that interacting proteins are sometimes fused into
1334-400: Is one where the interaction results in one of the proteins being activated. Conversely, a negative interaction indicates that one of the proteins being inactivated. Protein–protein interaction networks are often constructed as a result of lab experiments such as yeast two-hybrid screens or 'affinity purification and subsequent mass spectrometry techniques. However these methods do not provide
1392-964: Is readily accessible through the internet and is becoming a powerful resource for collecting known protein–protein interactions (PPIs), PPI prediction and protein docking. Text mining is much less costly and time-consuming compared to other high-throughput techniques. Currently, text mining methods generally detect binary relations between interacting proteins from individual sentences using rule/pattern-based information extraction and machine learning approaches. A wide variety of text mining applications for PPI extraction and/or prediction are available for public use, as well as repositories which often store manually validated and/or computationally predicted PPIs. Text mining can be implemented in two stages: information retrieval , where texts containing names of either or both interacting proteins are retrieved and information extraction, where targeted information (interacting proteins, implicated residues, interaction types, etc.)
1450-465: Is referred to as a multimer. When a multimer is formed from polypeptides produced by two different mutant alleles of a particular gene, the mixed multimer may exhibit greater functional activity than the unmixed multimers formed by each of the mutants alone. In such a case, the phenomenon is referred to as intragenic complementation (also called inter-allelic complementation). Intragenic complementation has been demonstrated in many different genes in
1508-529: The Gal4 DNA-binding domain (DB) and a second protein (Y) is fused to the Gal4 activation domain (AD). In the assay, yeast cells are transformed with these constructs. Transcription of reporter genes does not occur unless bait (DB-X) and prey (AD-Y) interact with each other and form a functional Gal4 transcription factor. Thus, the interaction between proteins can be inferred by the presence of the products resultant of
1566-447: The angles and intensities of a beam of X-rays diffracted by crystalline atoms are detected in a film, thus producing a three-dimensional picture of the density of electrons within the crystal. Later, nuclear magnetic resonance also started to be applied with the aim of unravelling the molecular structure of protein complexes. One of the first examples was the structure of calmodulin-binding domains bound to calmodulin . This technique
1624-476: The binding efficiency of DNA. Biotinylated plasmid DNA was bound by avidin. New protein was synthesized by using cell-free expression system i.e. rabbit reticulocyte lysate (RRL), and then the new protein was captured through anti-GST antibody bounded on the slide. To test protein–protein interaction, the targeted protein cDNA and query protein cDNA were immobilized in a same coated slide. By using in vitro transcription and translation system, targeted and query protein
1682-400: The binding of the electron transfer protein adrenodoxin to its reductase were identified as two basic Arg residues on the surface of the reductase and two acidic Asp residues on the adrenodoxin. More recent work on the phylogeny of the reductase has shown that these residues involved in protein–protein interactions have been conserved throughout the evolution of this enzyme. The activity of
1740-611: The case of the nuclear pore importins). In many biosynthetic processes enzymes interact with each other to produce small compounds or other macromolecules. Physiology of muscle contraction involves several interactions. Myosin filaments act as molecular motors and by binding to actin enables filament sliding. Furthermore, members of the skeletal muscle lipid droplet-associated proteins family associate with other proteins, as activator of adipose triglyceride lipase and its coactivator comparative gene identification-58, to regulate lipolysis in skeletal muscle To describe
1798-476: The cell is regulated by extracellular signals. Signal propagation inside and/or along the interior of cells depends on PPIs between the various signaling molecules. The recruitment of signaling pathways through PPIs is called signal transduction and plays a fundamental role in many biological processes and in many diseases including Parkinson's disease and cancer. A protein may be carrying another protein (for example, from cytoplasm to nucleus or vice versa in
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1856-419: The combination of weaker bonds, such as hydrogen bonds , ionic interactions, Van der Waals forces , or hydrophobic bonds. Water molecules play a significant role in the interactions between proteins. The crystal structures of complexes, obtained at high resolution from different but homologous proteins, have shown that some interface water molecules are conserved between homologous complexes. The majority of
1914-471: The communication between heterologous proteins is even more evident during cell signaling events and such interactions are only possible due to structural domains within the proteins (as described below). Stable interactions involve proteins that interact for a long time, taking part of permanent complexes as subunits, in order to carry out functional roles. These are usually the case of homo-oligomers (e.g. cytochrome c ), and some hetero-oligomeric proteins, as
1972-472: The composition of protein surfaces, rather than the protein cores, in spite of being frequently enriched in hydrophobic residues, particularly in aromatic residues. PPI interfaces are dynamic and frequently planar, although they can be globular and protruding as well. Based on three structures – insulin dimer, trypsin -pancreatic trypsin inhibitor complex, and oxyhaemoglobin – Cyrus Chothia and Joel Janin found that between 1,130 and 1,720 Å of surface area
2030-670: The conventional complexes, as enzyme-inhibitor and antibody-antigen, interactions can also be established between domain-domain and domain-peptide. Another important distinction to identify protein–protein interactions is the way they have been determined, since there are techniques that measure direct physical interactions between protein pairs, named “binary” methods, while there are other techniques that measure physical interactions among groups of proteins, without pairwise determination of protein partners, named “co-complex” methods. Homo-oligomers are macromolecular complexes constituted by only one type of protein subunit . Protein subunits assembly
2088-411: The current knowledge on biochemical cascades and molecular etiology of disease, as well as the discovery of putative protein targets of therapeutic interest. In many metabolic reactions, a protein that acts as an electron carrier binds to an enzyme that acts as its reductase . After it receives an electron, it dissociates and then binds to the next enzyme that acts as its oxidase (i.e. an acceptor of
2146-417: The data is that polypeptide monomers are often aligned in the multimer in such a way that mutant polypeptides defective at nearby sites in the genetic map tend to form a mixed multimer that functions poorly, whereas mutant polypeptides defective at distant sites tend to form a mixed multimer that functions more effectively. Direct interaction of two nascent proteins emerging from nearby ribosomes appears to be
2204-434: The difficult task of visualizing molecular interaction networks and complement them with other types of data. For instance, Cytoscape is an open-source software widely used and many plugins are currently available. Pajek software is advantageous for the visualization and analysis of very large networks. Identification of functional modules in PPI networks is an important challenge in bioinformatics. Functional modules means
2262-412: The electron). These interactions between proteins are dependent on highly specific binding between proteins to ensure efficient electron transfer. Examples: mitochondrial oxidative phosphorylation chain system components cytochrome c-reductase / cytochrome c / cytochrome c oxidase; microsomal and mitochondrial P450 systems. In the case of the mitochondrial P450 systems, the specific residues involved in
2320-417: The fewest total protein interactions recorded as they do not integrate data from multiple other databases, while prediction databases have the most because they include other forms of evidence in addition to experimental. For example, the primary database IntAct has 572,063 interactions, the meta-database APID has 678,000 interactions, and the predictive database STRING has 25,914,693 interactions. However, it
2378-400: The gene. Separately, the mutants were tested in pairwise combinations to measure complementation. An analysis of the results from such studies led to the conclusion that intragenic complementation, in general, arises from the interaction of differently defective polypeptide monomers to form a multimer. Genes that encode multimer-forming polypeptides appear to be common. One interpretation of
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2436-400: The identification of pairwise PPIs (binary method) in vivo , in which the two proteins are tested for biophysically direct interaction. The Y2H is based on the functional reconstitution of the yeast transcription factor Gal4 and subsequent activation of a selective reporter such as His3. To test two proteins for interaction, two protein expression constructs are made: one protein (X) is fused to
2494-771: The integration of primary databases information, but can also collect some original data. Prediction databases include many PPIs that are predicted using several techniques (main article). Examples: Human Protein–Protein Interaction Prediction Database (PIPs), Interlogous Interaction Database (I2D), Known and Predicted Protein–Protein Interactions (STRING-db) , and Unified Human Interactive (UniHI). The aforementioned computational methods all depend on source databases whose data can be extrapolated to predict novel protein–protein interactions . Coverage differs greatly between databases. In general, primary databases have
2552-417: The interacting proteins either being 'activated' or 'repressed'. Such effects can be indicated in a PPI network by "signs" (e.g. "activation" or "inhibition"). Although such attributes have been added to networks for a long time, Vinayagam et al. (2014) coined the term Signed network for them. Signed networks are often expressed by labeling the interaction as either positive or negative. A positive interaction
2610-502: The interface that enables the interaction between proteins. When characterizing PPI interfaces it is important to take into account the type of complex. Parameters evaluated include size (measured in absolute dimensions Å or in solvent-accessible surface area (SASA) ), shape, complementarity between surfaces, residue interface propensities, hydrophobicity, segmentation and secondary structure, and conformational changes on complex formation. The great majority of PPI interfaces reflects
2668-432: The interface water molecules make hydrogen bonds with both partners of each complex. Some interface amino acid residues or atomic groups of one protein partner engage in both direct and water mediated interactions with the other protein partner. Doubly indirect interactions, mediated by two water molecules, are more numerous in the homologous complexes of low affinity. Carefully conducted mutagenesis experiments, e.g. changing
2726-561: The mating-based ubiquitin system (mbSUS). The system detects membrane proteins interactions with extracellular signaling proteins Of the 705 integral membrane proteins 1,985 different interactions were traced that involved 536 proteins. To sort and classify interactions a support vector machine was used to define high medium and low confidence interactions. The split-ubiquitin membrane yeast two-hybrid system uses transcriptional reporters to identify yeast transformants that encode pairs of interacting proteins. In 2006, random forest , an example of
2784-493: The receptor-ligand binding. Interactions between intrinsically disordered protein regions to globular protein domains (i.e. MoRFs ) are transient interactions. Covalent interactions are those with the strongest association and are formed by disulphide bonds or electron sharing . While rare, these interactions are determinant in some posttranslational modifications , as ubiquitination and SUMOylation . Non-covalent bonds are usually established during transient interactions by
2842-461: The reporter gene expression. In cases in which the reporter gene expresses enzymes that allow the yeast to synthesize essential amino acids or nucleotides, yeast growth under selective media conditions indicates that the two proteins tested are interacting. Recently, software to detect and prioritize protein interactions was published. Despite its usefulness, the yeast two-hybrid system has limitations. It uses yeast as main host system, which can be
2900-509: The so-called interactomics of the organism, while aberrant PPIs are the basis of multiple aggregation-related diseases, such as Creutzfeldt–Jakob and Alzheimer's diseases . PPIs have been studied with many methods and from different perspectives: biochemistry , quantum chemistry , molecular dynamics , signal transduction , among others. All this information enables the creation of large protein interaction networks – similar to metabolic or genetic/epigenetic networks – that empower
2958-621: The subunits of ATPase . On the other hand, a protein may interact briefly and in a reversible manner with other proteins in only certain cellular contexts – cell type , cell cycle stage , external factors, presence of other binding proteins, etc. – as it happens with most of the proteins involved in biochemical cascades . These are called transient interactions. For example, some G protein–coupled receptors only transiently bind to G i/o proteins when they are activated by extracellular ligands, while some G q -coupled receptors, such as muscarinic receptor M3, pre-couple with G q proteins prior to
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#17330925132873016-621: The tagged protein, which is expressed in the cell usually at in vivo concentrations, and its interacting proteins (affinity purification). One of the most advantageous and widely used methods to purify proteins with very low contaminating background is the tandem affinity purification , developed by Bertrand Seraphin and Matthias Mann and respective colleagues. PPIs can then be quantitatively and qualitatively analysed by mass spectrometry using different methods: chemical incorporation, biological or metabolic incorporation (SILAC), and label-free methods. Furthermore, network theory has been used to study
3074-767: The title EYA . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=EYA&oldid=1008343271 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages EYA1 14048 ENSG00000104313 ENSMUSG00000025932 Q99502 P97767 NM_172060 NM_001370333 NM_001370334 NM_001370335 NM_001370336 NM_001252192 NM_010164 NM_001310459 NP_001357262 NP_001357263 NP_001357264 NP_001357265 NP_001389590 NP_001389591 Eyes absent homolog 1
3132-452: The types of protein–protein interactions (PPIs) it is important to consider that proteins can interact in a "transient" way (to produce some specific effect in a short time, like signal transduction) or to interact with other proteins in a "stable" way to form complexes that become molecular machines within the living systems. A protein complex assembly can result in the formation of homo-oligomeric or hetero-oligomeric complexes . In addition to
3190-439: The whole set of identified protein–protein interactions in cells. This system was first developed by LaBaer and colleagues in 2004 by using in vitro transcription and translation system. They use DNA template encoding the gene of interest fused with GST protein, and it was immobilized in the solid surface. Anti-GST antibody and biotinylated plasmid DNA were bounded in aminopropyltriethoxysilane (APTES)-coated slide. BSA can improve
3248-453: Was removed from contact with water indicating that hydrophobicity is a major factor of stabilization of PPIs. Later studies refined the buried surface area of the majority of interactions to 1,600±350 Å . However, much larger interaction interfaces were also observed and were associated with significant changes in conformation of one of the interaction partners. PPIs interfaces exhibit both shape and electrostatic complementarity. There are
3306-410: Was synthesized by the same extract. The targeted protein was bound to array by antibody coated in the slide and query protein was used to probe the array. The query protein was tagged with hemagglutinin (HA) epitope. Thus, the interaction between the two proteins was visualized with the antibody against HA. When multiple copies of a polypeptide encoded by a gene form a complex, this protein structure
3364-846: Was the Database of Interacting Proteins (DIP) . Primary databases collect information about published PPIs proven to exist via small-scale or large-scale experimental methods. Examples: DIP , Biomolecular Interaction Network Database (BIND), Biological General Repository for Interaction Datasets ( BioGRID ), Human Protein Reference Database (HPRD), IntAct Molecular Interaction Database, Molecular Interactions Database (MINT), MIPS Protein Interaction Resource on Yeast (MIPS-MPact), and MIPS Mammalian Protein–Protein Interaction Database (MIPS-MPPI).< Meta-databases normally result from
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