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

Abstract

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.

Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity

“…1C). Accordingly, it has been shown that CHD5 is predominantly expressed within the nuclei of cultured human fibroblasts derived from fetal endocardial tissue (Egeo et al, 1998). We identified a putative Xenopus CHD5 EST and confirmed the clone to be full length ( Fig.…”

“…CHD5 was first identified as a nuclear-localized cardiac-expressed gene contained in a restricted region of chromosome 21 triplicated in individuals with DS (Egeo et al, 1998) and later found to localize to the nuclei of medaka fish cardiomyocytes (Murata et al, 2009). Interestingly, work on the yeast homolog of CHD5, MDM39, has identified synthetic interactions with Spf1p, a P-type ATPase involved in protein transport of charged molecules across the ER membrane (Ando and Suzuki, 2005).…”

“…Among the candidate genes is that encoding congenital heart disease protein 5 (CHD5), also known as tryptophan-rich basic protein (WRB). CHD5, initially identified in a screen for genes within a restricted region of chromosome 21 associated with heart disease in individuals with DS, was found to be expressed in fetal hearts and shown to localize predominately to the nuclei of cells of cardiac origin (Egeo et al, 1998). CHD5 was also identified in a drug-sensitized screen in zebrafish as a regulator of myocardial repolarization (Milan et al, 2009) and depletion of CHD5 in medaka fish has been reported to be associated with general cardiac defects of unknown etiology (Murata et al, 2009).…”

SH3BGRL3 Protein as a Potential Prognostic Biomarker for Urothelial Carcinoma: A Novel Binding Partner of Epidermal Growth Factor Receptor

“…The amino acid sequence of SH3BGRL3 belongs to the thioredoxin superfamily and is highly similar to Escherichia coli GRX1 (10), an enzyme with oxidoreductase activity. Although SH3BGRL3 protein is homologous to Nterminal region of the SH3BGR protein (10,11), it lacks the conserved SH3-binding motif, implying that it has a different function to those of other subfamily members. SH3BGRL3 could inhibit TNFa-induced apoptosis and promote cell survival, although the molecular mechanism underlying these functions remains unclear (12).…”

Down syndrome congenital heart disease: A narrowed region and a candidate gene

“…At present, potential candidates known to be expressed in the fetal heart include SH3BGR, 48 DSCR2 49 (described as CHD 1 in Hubert et al, 50 WRB, 51 and HES1. 52 SH3BGR encodes a glutamic acidrich protein containing an SH3-binding domain whose expression is ubiquitous but highest in heart and skeletal muscle 48 (Lyons and Korenberg, unpublished data); DSCR2 encodes a leucine-rich protein thought to function in cell proliferation, which is expressed in adult heart, skeletal muscle, and other tissues; 49 WRB encodes a tryptophan-rich basic protein with a potential nuclear localization signal, which is expressed in adult heart, brain, skeletal muscle, and other tissues, and fetal brain, lung, liver, and kidney; 51 and HES1 is thought to function in cellular metabolism and is highly expressed in heart and skeletal muscle. 52 Others of the known and predicted genes in the region may be shown to contribute to the DS cardiac phenotype.…”