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P Arrigo

Publications and source records attributed to P Arrigo.

11 recordsLinked to original sources

A novel human homologue of the SH3BGR gene encodes a small protein similar to Glutaredoxin 1 of Escherichia coli.

Glutaredoxins (GRXs) are ubiquitous GSH-dependent oxidoreductases, which catalyze the reduction of protein-glutathionyl-mixed disulfides and are considered to play an important role in the enzymatic regulation of redox-sensitive proteins. In this paper, we describe the identification and characterization of a new human homologue of the SH3BGR gene, named SH3BGRL3 (SH3 domain binding glutamic acid-rich protein like 3). SH3BGRL3 is widely expressed and codes for a highly conserved small protein, which shows a significant similarity to Glutaredoxin 1 (GRX1) of Escherichia coli and is predicted to belong to the Thioredoxin Superfamily. However, the SH3BGRL3 protein lacks both the conserved cysteine residues, which characterize the enzymatic active site of GRX. This structural feature raises the possibility that SH3BGRL3 could function as an endogenous modulator of GRX biological activity. EGFP-SH3BGRL3 fusion protein expressed in COS-7 cells localizes both to the nucleus and to the cytoplasm. The SH3BGRL3 gene was mapped to chromosome 1p34.3-35.

Amino Acid Sequence↗

Can functional regions of proteins be predicted from their coding sequences? The case study of G-protein coupled receptors.

A filter based on a set of unsupervised neural networks trained with a winner-take-all strategy discloses signals along the coding sequences of G-protein coupled receptors. By comparing with the existing experimental data it appears that these signals correlate with putative functional domains of the proteins. After protein alignment within subfamilies, signals cluster in protein regions which, according to the presently available experimental results, are described as possible functional domains of the folded proteins. The mapping procedure reveals characteristic regions in the coding sequences common and/or characteristic of the receptor subtype. This is particularly noticeable for the third cytoplasmic loop, which is likely to be involved in the molecular coupling of all the subfamilies with G-proteins. The results indicate that our mapping can highlight intrinsic representative features of the coding sequences which, in the case of G-protein coupled receptors, are characteristic of protein functional regions and suggest a possible application of the filter for predicting functional determinants in proteins starting from the coding sequence.

Amino Acid Sequence↗

Identification and characterization of a new human gene encoding a small protein with high homology to the proline-rich region of the SH3BGR gene.

As part of an effort to identify genes potentially involved in the Down Syndrome pathogenesis, in this paper we report the identification and characterization of a new human gene (named SH3BGRL), which shows a high homology to the SH3BGR gene, previously mapped to the Down Syndrome region of chromosome 21. The SH3BGRL gene encodes for a small protein of 114 amino acids, sharing 60% identity and 84% conservation on the amino acid level with the middle, proline-rich region of the SH3BGR gene and containing a similar SH3 (Scr homology 3) binding motif. The SH3BGRL and the proline-rich region of SH3BGR proteins appear to be highly conserved, sharing 95 and 98% identity, respectively, with the mouse homologues. A 1.9 kb transcript of the SH3BGRL gene has been found in all the tissues examined, in contrast with the expression pattern of the SH3BGR gene which is transcribed only in heart and skeletal muscle. The SH3BGR gene and its homologue, SH3BGRL, could be members of a new family of genes containing a highly conserved proline-rich functional domain. The SH3BGRL gene has been mapped by fluorescent in situ hybridization to Chromosome Xq13.3.

Amino Acid Sequence↗

Identification and characterization of a new human cDNA from chromosome 21q22.3 encoding a basic nuclear protein.

Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients. The region proposed to contain the gene(s) for DS CHD has been restricted to 21q22.2-22.3, from D21S55 to MX1. The identification and functional characterization of the genes mapping to this region is a necessary step to understand the pathogenesis of CHD in DS. In an effort to contribute to the construction of a transcriptional map of the DS CHD region we have performed direct cDNA selection using a YAC contig that maps between ETS2 and D21S15 and cDNAs synthesised from fetal heart structures. Here we describe the identification and characterization of a new gene, WRB, that maps to 21q22.3 between ACTL5 and HMG 14 and appears to be widely expressed in adult and fetal tissues. The new gene encodes a basic protein of unknown function containing a tryptophan-rich carboxyl-terminal region and a potential nuclear localization signal. Immunofluorescence analysis shows a predominant localization in the cell nucleus. The understanding of the biological function of the protein product should clarify the potential role of WRB in the pathogenesis of DS CHD.

Adult↗

Cloning a new human gene from chromosome 21q22.3 encoding a glutamic acid-rich protein expressed in heart and skeletal muscle.

The identification and functional characterization of genes on chromosome 21 is a necessary step to understand the pathogenesis of the various phenotypic anomalies that affect Down syndrome patients. Using direct cDNA selection we have identified a new gene, SH3BGR, that maps to 21q22.3, proximal to HMG14, and is differentially expressed in heart and skeletal muscle. SH3BGR encodes a novel protein that is characterized by the presence of a proline-rich region containing the consensus sequence for a SH3-binding domain and by an acidic carboxyl-terminal region containing a glutamic acid-rich domain predicted to assume a coiled coil. The presence of two functional domains involved in protein-protein interactions suggests that SH3BGR could be part of a multimeric complex. Its overexpression might alter specific functions of muscular tissue and therefore take part in the pathophysiology of muscular hypotonia in Down syndrome.

Adult↗

Self-organizing neural maps of the coding sequences of G-protein-coupled receptors reveal local domains associated with potentially functional determinants in the proteins.

Mapping of the coding sequences of the best characterized subfamilies of G-protein-coupled receptors is performed with unsupervised neural networks based on a winner-take-all strategy. High order features therefrom extracted originate signals along the aligned protein sequences of the different subfamilies. These plots reveal characteristic domains common and/or characteristic of the receptor subfamily. By comparison with the existing experimental results, it is obtained that most of the regions signalled by clustering overlap with possible functional regions in the folded proteins. This is particularly noticeable for the third cytoplasmic loop, which is likely to be involved in the molecular coupling with the G-proteins. The results suggest that functional regions in proteins may be characterized by intrinsic representative features in the coding sequences which can be enlighted by high order mapping.

Binding Sites↗

Hamming-Clustering method for signals prediction in 5' and 3' regions of eukaryotic genes.

MOTIVATION: Gene expression is regulated by different kinds of short nucleotide domains. These features can either activate or terminate the transcription process. To predict the signal sites in the 5' and 3' gene regions we applied the Hamming-Clustering network (HC) to the TATA box, to the transcription initiation site and to the poly(A) signal determination in DNA sequences. This approach employs a technique deriving from the synthesis of digital networks in order to generate prototypes, or rules, which can be directly analysed or used for the construction of a final neural network. RESULTS: More than 1000 poly-A signals have been extracted from EMBL database rel. 42 and used to build the training and the test set. A full set of the eukaryotic genes (1252 entry) from the Eukaryotic Promoter Database (EPD rel. 42) have been used for the TATA-box signal and transcription network approach. The results show the applicability of the Hamming-Clustering method to functional signal prediction.

Algorithms↗

Potentially functional regions of nucleic acids recognized by a Kohonen's self-organizing map.

Computer recognition of short functional sites on DNA, such as promoter regions or intron-exon boundaries, has recently attracted much interest. In this paper we have focused our attention on the automatic recognition of relevant features of human nucleic acid sequences by means of an unsupervised artificial neural network model. Sixty messenger RNA and 31 genomic DNA sequences were analysed. The results showed that in mRNA, the minimal similarity 60 base pattern was guanine- and cytosine-rich and located in most sequences in a range of 250 bases from either the middle point of the signal peptide coding region or from the start of the coding region. On DNA sequences a region defined by a cluster of minimal similarity patterns was present in many of the analysed genes. This zone may be related to alternative splicing and DNA methylation.

Algorithms↗

Identification of a new motif on nucleic acid sequence data using Kohonen's self-organizing map.

Here we present a performance test of a Kohonen features map applied to the fast extraction of uncommon sequences from the coding region of the human insulin receptor gene. We used a network with 30 neurons and with a variable input window. The program was aimed at detecting unique or uncommon DNA regions present in crude sequence data and was able to automatically detect the signal peptide coding regions of a set of human insulin receptor gene data. The testing of this program with HSIRPR cDNA release (EMBL data bank) indicated the presence of unique features in the signal peptide coding region. On the basis of our results this program can automatically detect 'singularity' from crude sequencing data and it does not require knowledge of the features to be found.

Algorithms↗

[Computer program recognition of a cDNA sequence specifying signal peptides].

An application of a computational analysis of cDNA sequences is presented in this paper. The goal is the identification of functional domains on sequence data. The results show the capability of this technique to identify a zone of DNA associated with the signal peptide coding region, whose biological function at DNA or RNA level is still unknown.

Base Sequence↗