Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protein function prediction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1994

Tumor suppressor and overgrowth suppressor genes of Drosophila melanogaster: developmental aspects.

In Drosophila about 27 developmental genes have been identified which suppress tumorous growth and about as many genes are known to suppress overgrowth. Recessive lethal mutations in tumor suppressor genes block in one step the differentiation of specific target cells, leaving unaffected their capacity to divide in an autonomous, malignant and lethal fashion. The structural analysis of eight tumor suppressor genes predicts putative functions in differentiation events, such as cell-cell communication, protein transport and protein synthesis, signal transduction, sex determination splicing and cytokinesis. Their predicted products function as effectors of the differentiated state being vital components of cell junctions, the cytoskeleton, the protein synthetic apparatus, the splicing machinery and signal transduction. In contrast to the tumor suppressor genes, which are instrumental in the establishment and maintenance of the differentiated state, overgrowth suppressor genes seem to control cell-specific division rates while leaving unaffected the capacity of the cells to differentiate. The Drosophila tumor suppressor and overgrowth suppressor genes show clearly the mutual exclusion of the genetic programs controlling cell division and cell differentiation. Some of the genes exhibit homologies to mammalian genes. Their functional homology, however, is still an open question.

Animals↗
PubMed1989

The completed sequence of lymphocytic choriomeningitis virus reveals a unique RNA structure and a gene for a zinc finger protein.

The arenavirus, lymphocytic choriomeningitis virus (LCMV) has a single-stranded RNA genome composed of a large (L) and a small (S) RNA segment. The completed sequence of LCMV, presented here, reveals a formerly unknown gene (Z) on the L genomic segment. This gene is encoded in the positive or message-sense of the viral genomic RNA, whereas the adjacent gene (L) is in the genome-complementary, or negative sense. The ambisense polarity of the genes on the L RNA reiterates the polarity of genes on the small (S) genomic segment. The Z gene encodes a 10-kDa protein containing a single zinc-finger sequence (Cys2His2). A small RNA representing the message sense of the Z gene is found in infected cells and within virions. In contrast to the known LCMV proteins having structural or enzymatic functions, the predicted Z gene product is most likely to be an RNA-binding protein with a regulatory role. The encapsidation of a message sense Z RNA suggests a role for this gene immediately following virus penetration. The L/Z intergenic region is rich in cytidylic acid (C) and presents an unusual RNA structure. All cDNA clones of the intergenic region differ from each other within a certain poly(C) stretch and lack a 30-base region present in the direct RNA sequence. Finally, the completed sequence establishes that the L RNA 5' end is complementary to its 3' end. The L RNA termini, similar to the S RNA termini, have a small but potentially important asymmetry of sequence. LCMV is the first arenavirus to be completely sequenced.

Amino Acid Sequence↗
PubMed1991

Deletion and duplication of specific sequences in the K88ab fimbrial subunit protein from porcine enterotoxigenic Escherichia coli.

Small, defined in-frame deletions and in-frame duplications of specific sequences were made within the faeG gene encoding the K88ab fimbrial subunit protein from porcine enterotoxigenic Escherichia coli. The cellular localization and proteolytic stability of the different mutated fimbrial subunit proteins were determined, and compared with those of the wild-type protein. Based upon these results, we predict a functional role of specific structures in the K88ab fimbrial subunit protein in subunit-subunit interactions as well as in interactions between FaeG and the other proteins encoded by the K88ab operon. The results obtained were further compared with results obtained from operon deletions, linker insertion mutagenesis and the current model for biogenesis of K88 fimbriae. One of the mutated fimbrial subunit genes was used to construct a secreted in-frame fusion between FaeG and a characterized epitope (lacking cysteine) from the Hepatitis B pre-S2 protein. Such fusion proteins might be useful in the design of recombinant vaccines.

Amino Acid Sequence↗
PubMed1989

Determinants of site-specific recombination in the lambdoid coliphage HK022. An evolutionary change in specificity.

The temperate bacteriophage HK022, like its relative lambda, inserts its chromosome into a specific site in the bacterial chromosome during lysogenization and excises it after induction. However, we find that the recombinational specificities of the two phages differ: they use different bacterial sites, and neither promotes efficient insertion or excision of the other phage chromosome. In order to determine the basis for this difference in specificity, we sequenced the HK022 elements that are involved in insertion and excision, and compared them to the corresponding lambda elements. The location, orientation, size and overall arrangement of the int and xis genes and the phage attachment sites are nearly identical in the two genomes, as is common for other functionally related elements in lambdoid phages. The Xis proteins of the two phages are functionally interchangeable, and their predicted amino acid sequences differ by but one residue. In contrast, the two Int proteins are not functionally interchangeable, and their sequences, although similar, differ at many positions. These sequence differences are not uniformly distributed: the amino-terminal 55 residues are completely conserved, but the remaining 302 show a pattern of differences interspersed with identities and conservative changes. These findings imply that the specificity difference between HK022 and lambda site-specific recombination is a consequence of the inability of the respective Int proteins to recognize pairs of heterologous attachment sites. The two phage attachment sites are remarkably similar, especially the two "arm" segments, which in lambda contain binding sites for Int, Xis and integration host factor. They are less similar in the segment between the two arms, which in lambda contains the points of recombinational strand exchange and a second class of binding site for Int protein (the "core-type" sites). The two bacterial attachment sites are quite different, although both have a short stretch of perfect homology with their respective phage partners at the points of strand exchange. We propose that the two Int proteins recognize similar or identical sites in the arms of their cognate attachment sites, and that differences in binding or action at the core-type sites is responsible for the divergent specificities. Genetic experiments and sequence comparisons suggest that both proteins recognize different but overlapping families of core-type sites, and that divergence in specificity has been achieved by an alternating succession of small, mutually compatible changes in protein and site.

Amino Acid Sequence↗
PubMed1994

Predicting the conformation of proteins from sequences. Progress and future progress.

A new paradigm for predicting the secondary and tertiary structure of functional proteins from sequence data has emerged from detailed models of how natural selection, conservation, and neutral drift, the three fundamental factors in molecular evolution, leave their mark upon protein sequences. Structural information is extracted from a set of aligned homologous sequences via an analysis of patterns of conservation and variation between proteins with quantitatively defined evolutionary relationships. Tertiary structural information is obtained prior to the assignment of secondary structure, where it plays an important role. Throughout, structural predictions are made with the active involvement of a biochemist whose expertise and insight is critical both for making the prediction and in analyzing its successful and unsuccessful parts. Secondary structure predictions are evaluated based on their ability to sustain an effort to model tertiary structure. Several predictions made using the new paradigm can now be compared with those made under the classical paradigm, including a neural network. The results obtained from the new paradigm are clearly superior to those obtained with the classical paradigm, at least within the protein families that were examined.

Amino Acid Sequence↗
PubMed1993

The N-terminal protein of the polyprotein encoded by the potyvirus tobacco vein mottling virus is an RNA-binding protein.

The first predicted polypeptide encoded by the potyvirus tobacco vein mottling virus (TVMV) is a highly positively charged protein of predicted M(r) 29K that functions as a protease to perform the first predicted cleavage in the potyvirus polyprotein. We expressed this protein (P1pro) fused with glutathione S-transferase (GST) and purified the fusion protein from engineered Escherichia coli. We found that the intact fusion protein, as well as samples in which the P1pro portion was liberated from GST by pretreatment with thrombin, was able to bind RNA. Binding activity was optimal at relatively high KCl concentrations, suggesting an interaction dependent on a specific protein structure and not just on the binding of the negatively charged phosphate backbone by the positively charged P1pro polypeptide. The TVMV P1pro preferred ssRNA over DNA or dsRNA, and showed a possible preference for sequences containing oligo(G) tracts. Like other potyvirus-encoded proteins, the TVMV P1pro therefore possesses more than one demonstrable biochemical activity and probably plays multiple roles in the TVMV life cycle.

Amino Acid Sequence↗
PubMed1995

Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y).

In this paper, we investigate DNA bending induced by proteins required for virus induction of the human interferon-beta (IFN beta) gene. We show that NF-kappa B-DNA complexes that are functionally distinct in the context of the IFN beta enhancer are also conformationally distinct and that two sites in the enhancer contain in-phase bends that are counteracted or reversed by the binding of NF-kappa B, ATF-2/c-Jun, and HMG I(Y). Strikingly, this modulation of intrinsic enhancer architecture results in an orientation that favors predicted protein-protein interactions in a functional nucleoprotein complex, the enhanceosome. Furthermore, the subtle modulation of DNA structure by HMG I(Y) in this process distinguishes it from other architectural factors.

Activating Transcription Factor 2↗
PubMed1984

Modification of plant proteins by immobilized proteases.

A potential application of plant proteins could be a replacement of animal proteins now in use in the food industry on the basis of certain specific functional properties plant proteins have. Modification of the chemical structure of selected plant proteins is needed to replace more expensive animal proteins as food ingredients that have specific functional characteristics. Structure modification may be achieved by physical, chemical, or microbiological methods, or by a combination of these. Immobilized enzyme techniques offer significant advantages for protein modification. Knowledge of the molecular properties of plant proteins is essential to understand the basis of protein functionality, to modify proteins so that they acquire desirable functional properties, and to predict potential applications of modified plant proteins. This paper reviews all the above mentioned aspects of plant protein chemistry and potential utilization.

Amino Acids↗
PubMed1988

Cloning and sequencing of the yeast gene for dolichol phosphate mannose synthase, an essential protein.

Dolichol phosphate mannose (Dol-P-Man) synthase (EC 2.4.1.83) catalyzes the formation of Dol-P-Man from Dol-P and GDP-Man. The structural gene for yeast Dol-P-Man synthase (DPM1) was isolated by screening a yeast genomic DNA library for colonies that overexpressed Dol-P-Man synthase activity. This approach relied on a method to screen for Dol-P-Man synthase activity in lysed yeast colonies and used a yeast mutant with very low Dol-P-Man synthase activity in colony lysates. Transformants isolated using this technique expressed Dol-P-Man synthase activity 9-14-fold higher than that of a wild type strain, and all seven plasmids conferring this overproduction had a common region in their yeast genomic DNA insert. DPM1 is the structural gene for yeast Dol-P-Man synthase since Escherichia coli transformants harboring this gene express Dol-P-Man synthase activity in vitro. DNA sequencing of the DPM1 gene revealed an open reading frame of 801 bases. The 30-kDa size of the predicted protein is in excellent agreement with the size of the purified yeast enzyme (Haselbeck, A., and Tanner, W. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 1520-1524). Analysis of the predicted amino acid sequence reveals the protein has a potential membrane spanning domain of 25 amino acids at its COOH terminus. The protein's NH2 terminus, though not hydrophobic, meets existing criteria for yeast signal sequences, but there is no site for cleavage by signal peptidase. If the NH2 terminus is a functional signal sequence, the protein is predicted to be oriented toward the lumen of the endoplasmic reticulum with both NH2 and COOH termini serving as membrane anchors. If there is no signal sequence, the enzyme is predicted to face the cytoplasm and be anchored only by its COOH terminus. The DPM1 gene is essential for viability in yeast since disruption of the gene is lethal. We suspect Dol-P-Man synthase is not an essential protein due to its role in N-glycosylation since mutations in other genes that affect the late steps in lipid-linked oligosaccharide synthesis do not affect cell growth. Instead, DPM1 may be an essential gene because its product is required for O-glycosylation in yeast or because Dol-P-Man synthase is needed in some unidentified pathway.

Alleles↗
PubMed1993

MRP-8 and MRP-14, two abundant Ca(2+)-binding proteins of neutrophils and monocytes.

Two calcium-binding proteins, named migration inhibitory factor-related proteins-8 (MRP-8) and MRP-14, are primarily expressed by circulating human neutrophils and monocytes. Evidence accumulating from the investigations of several independent groups is now leading to an improved understanding of the biology of these proteins. Both MRP-8 and MRP-14 display features characteristic of members of the S100 family of calcium-binding proteins. Some of these features predict functions for MRP-8 and MRP-14 but to date an exact and well-defined function remains elusive. Here we review the available information and highlight evidence that suggests the function of MRP-8 and MRP-14 may be associated with both monocyte and neutrophil activation and the accumulation of these cells in inflammatory sites.

Amino Acid Sequence↗
PubMed1994

Translational control mediates the developmental regulation of the Trypanosoma brucei Nrk protein kinase.

The expression and function of eukaryotic protein kinases is highly regulated, primarily through transcriptional and post-translational processes. In this report we demonstrate an unusual mechanism for controlling protein kinase function, translational control. The Trypanosoma brucei Nrk loci encode predicted protein kinases. Here we show that Nrk has protein serine-threonine kinase activity and examine the expression and activity of Nrk during parasite development. While Nrk transcripts were previously found to be constitutively expressed throughout the life cycle, we now find that expression of Nrk protein is highly stage-regulated. Immunoblot analysis revealed that Nrk expression dramatically increased as the parasites differentiated from proliferative slender bloodforms to the non-proliferative stumpy bloodforms. Procyclic form organisms expressed moderate levels of Nrk. Analysis of Nrk activity demonstrated that it too was highest in stumpy bloodforms. Metabolic labeling and pulse-chase analysis demonstrated that Nrk accumulation was highest in stumpy bloodforms and indicated that Nrk abundance is primarily controlled at the level of biosynthesis rather than turnover. All Nrk mRNA was contained in the poly(A)+ fraction, and the 5' ends of the transcript were the same in each developmental stage. Thus, Nrk is under translational control. The strict developmental regulation of the Nrk enzymes within the trypanosome life cycle suggests that the Nrk protein kinase may play a role in parasite differentiation.

Animals↗
PubMed1989

Structural and functional features of Drosophila chorion proteins s36 and s38 from analysis of primary structure and infrared spectroscopy.

Amino acid composition, Fourier transform analysis and secondary structure prediction methods strongly support a tripartite structure for Drosophila chorion proteins s36 and s38. Each protein consists of a central domain and two flanking 'arms'. The central domain contains tandemly repetitive peptides, which apparently generate a secondary structure of beta-sheet strands alternating with beta-turns, most probably, forming a twisted beta-pleated sheet or beta-barrel. The central domains of s36 and s38 share similarities, but they are recognizably different. The flanking 'arms', with different primary and secondary structure features, presumably serve protein-specific functions. The possible roles of the protein domains for the establishment of higher order structure in Drosophila chorion and the possible function of the molecules are discussed. The predicted secondary structure of Drosophila chorion proteins s36 and s38 is supported by experimental information obtained from Fourier transform infrared spectroscopic studies of Drosophila chorions.

Amino Acid Sequence↗
PubMed2025

Identification of IDH3G, encoding the gamma subunit of mitochondrial isocitrate dehydrogenase, as a novel candidate gene for X-linked retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerative disorders characterized by the loss of rod and cone photoreceptors, leading to visual impairment and blindness. To date, to our knowledge, X-linked RP has been associated with variants in 3 genes (RPGR, RP2, and OFD1), whereas genetic defects at 3 loci (RP6, RP24, and RP34) are yet unidentified. The aim of this study was to identify a novel candidate gene underlying X-linked RP. METHODS: Participants were identified from cohorts of genetically unsolved male individuals affected by RP, who underwent genome sequencing, exome sequencing, or candidate gene screening via direct Sanger sequencing at 3 referral centers. Specifically, 2 probands were identified at the National Reference Centre for Rare Retinal Diseases (Paris, France), 2 at the Massachusetts Eye and Ear Hospital (Boston, MA), and 1 at the National Reference Centre for Inherited Sensory Diseases (Montpellier, France). The pathogenicity of the identified variants was assessed using bioinformatic predictions, protein expression analyses, and mitochondrial function assays. RESULTS: We identified 4 rare single-nucleotide variants in IDH3G (HGNC:5386), located at the RP34 locus on the X chromosome, and a complete gene deletion, in 5 unrelated male individuals affected with nonsyndromic RP. The variants segregated with the phenotype in all available family members. In all cases, the disease severity was intermediate. None had high myopia. IDH3G encodes the γ subunit of mitochondrial isocitrate dehydrogenase (IDH3), an enzyme involved in the citric acid cycle, which is expressed in the inner segments of photoreceptors. Variants in IDH3A and IDH3B, encoding the other subunits of IDH3, have already been associated with nonsyndromic autosomal recessive RP. Bioinformatic predictions and functional assays support a pathogenic role for the variants identified in this study, possibly through partial loss of enzymatic activity and mitochondrial function. CONCLUSION: Our findings suggest that variants in IDH3G are a novel cause of X-linked RP.

Humans↗
PubMed1991

Protein phosphorylation and neuronal function.

Following the initial demonstration of phosphorylation of endogenous brain proteins (Johnson et al., 1971), two decades of work have shown that this biochemical mechanism represents one of the most important means by which extracellular signals are transduced into changes in neuronal functions. Evidence discussed in this review shows that neural cells contain a plethora of protein kinases, protein phosphatases, and phosphorylated proteins and that many of these systems appear essential for the regulation of cell functions as diverse as membrane excitability, neuronal secretory processes, cytoskeletal organization, neuronal morphology, and cellular metabolism. Moreover, there exists intricate functional relationships between many of the neuronal protein phosphorylation systems, which allow "cross-talk" between distinct signals to take place in various brain cells. The properties of protein phosphorylation systems allow these regulatory systems to influence events taking place on a microsecond scale (e.g., neurotransmitter release) and events lasting for hours and days (e.g., LTP). Our present knowledge concerning neuronal protein phosphorylation has also allowed studies to be initiated regarding the possible involvement of protein phosphorylation in various clinical disorders affecting signal transduction and brain function. It seems safe to predict that continued studies of neuronal protein phosphorylation systems will continue to improve our understanding of the anatomical, physiological, and pharmacological basis for nervous system function in both health and disease.

Animals↗
PubMed1993

p34cdc2 homologue is located in nucleoli of the nervous and endocrine systems.

p34cdc2 protein kinase is a component of M phase-promoting factor (MPF), which plays an important role in controlling the mitotic and meiotic cell cycle. p34cdc2 contains a unique 16 amino acid sequence (PSTAIR) that is conserved from fission yeast to human. Using polyclonal anti-PSTAIR antibody, we detected the p34cdc2 homologue in the central nervous system of adult mice by western blotting. By immunohistochemical technique, we found that the p34cdc2 homologue was located in the nucleoli of neurons and glia in the central and peripheral nervous systems. In the central nervous system, positive cells were widely distributed from the cerebral cortex to the spinal cord. Immunoreactive cells were also detected in retina and pituitary. The evidence that the p34cdc2 is present in neurons which have lost the ability of cell division predicts another function of p34cdc2 family proteins besides the one that has generally recognized.

Amino Acid Sequence↗
PubMed1994

Identification of functional domains in the plasma apolipoproteins by analysis of inter-species sequence variability.

Molecular evolution theory posits that sequence motifs essential for protein function are constrained by selective pressure from changing over long stretches of evolutionary time. Thus, analysis of inter-species amino acid sequence variability, by identifying highly conserved intervals, should predict the location of domains critical for protein function. We have analyzed the amino acid sequences of the mammalian apolipoproteins A-I, A-IV, C-I, C-II, C-III, D, and E with a computer algorithm that calculates numerical residue variability scores. The application of a median sieve filter to the data facilitated identification of the exact boundaries of highly conserved domains, which coincided with the location of known structural features and functional domains in this family of proteins. The analysis also identified highly conserved intervals in every apolipoprotein whose function is unknown at present, but which are candidates for regions with specific functional roles.

Amino Acid Sequence↗
PubMed1993

Regulation of the mitochondrial ATP synthase/ATPase complex: cDNA cloning, sequence, overexpression, and secondary structural characterization of a functional protein inhibitor.

The ATPase inhibitor protein of the rat liver mitochondrial ATP synthase/ATPase complex has been cloned from a rat liver cDNA library, and its nucleotide sequence determined. The sequence is highly homologous to both the bovine heart (approximately 70%) and the yeast inhibitor proteins (approximately 40%). The deduced protein sequence is 107 amino acids in length, and based on homology to the bovine heart protein, the first 25 N-terminal amino acids encode a putative mitochondrial targeting sequence. The "mature" protein (without the targeting sequence) fused to the maltose binding protein has been overexpressed in Escherichia coli. The maltose binding protein was used as a handle for the development of a rapid one-step purification of the fusion protein by affinity chromatography on an amylose resin. The purified fusion protein was cleaved with Factor Xa protease at the fusion junction, and the resulting ATPase inhibitor protein was purified to > 90% purity. The purified, overexpressed inhibitor protein displays normal inhibitor activity. The protein inhibits ATP hydrolysis catalyzed by the ATP synthase/ATPase complex in submitochondrial particles in a manner kinetically indistinguishable from the same protein purified from rat liver mitochondria, and exhibits a specific activity of approximately 10,000 units/mg. The secondary structure of the inhibitor protein was determined by circular dichroism spectropolarimetry. The experimentally determined structure shows a high content of alpha-helix and is in good agreement with sequence-based structural predictions. As the function of the inhibitor protein is known to exhibit a high dependence on pH, a study of the pH dependence of inhibitor secondary structure was performed. It is shown that as pH is lowered, conditions which activate inhibitory capacity, the protein loses significant alpha-helical structure. This is the first report of the overexpression in E. coli of a functional ATPase inhibitor protein. Secondary structural analysis of this protein indicates that conversion from its active to its inactive form involves a significant conformational change.

Adenosine Triphosphatases↗
PubMed1992

Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors.

The pathogenic Neisseria species are capable of utilizing transferrin as their sole source of iron. A neisserial transferrin receptor has been identified and its characteristics defined; however, the biochemical identities of proteins which are required for transferrin receptor function have not yet been determined. We identified two iron-repressible transferrin-binding proteins in Neisseria gonorrhoeae, TBP1 and TBP2. Two approaches were taken to clone genes required for gonococcal transferrin receptor function. First, polyclonal antiserum raised against TBP1 was used to identify clones expressing TBP1 epitopes. Second, a wild-type gene copy was cloned that repaired the defect in a transferrin receptor function (trf) mutant. The clones obtained by these two approaches were shown to overlap by DNA sequencing. Transposon mutagenesis of both clones and recombination of mutagenized fragments into the gonococcal chromosome generated mutants that showed reduced binding of transferrin to whole cells and that were incapable of growth on transferrin. No TBP1 was produced in these mutants, but TBP2 expression was normal. The DNA sequence of the gene encoding gonococcal TBP1 (tbpA) predicted a protein sequence homologous to the Escherichia coli and Pseudomonas putida TonB-dependent outer membrane receptors. Thus, both the function and the predicted protein sequence of TBP1 were consistent with this protein serving as a transferrin receptor.

Amino Acid Sequence↗