Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes

doi:10.1016/S0378-1119(02)00828-4

Gene

Volume 297, Issues 1–2, 4 September 2002, Pages 79-83

https://doi.org/10.1016/S0378-1119(02)00828-4 Get rights and content

Abstract

The fibronectin type III (FNIII) repeat is one of three structural motifs originally identified in the fibronectin protein and has been well characterized in recent years. The consensus sequence has since been found in many different proteins including receptors and cell adhesion molecules. We report the cloning and expression analysis of Frcp1 and Frcp2, two members of a new FNIII repeat containing gene family. During embryonic development both genes are primarily expressed in the brain. In adult tissues, Frcp1 is strongly expressed in the liver and Frcp2 in the heart.

Introduction

The extracellular matrix protein fibronectin plays an important role in cell adhesion. The protein contains fibronectin type I, II and III domains. All three domains have been well characterized. The fibronectin type III (FNIII) repeat is generally about 90 amino acids long and 15–17 of these repeats can be found in the fibronectin protein (Ruoslahti, 1988). A characteristic of FNIII repeats is the presence of conserved tryptophan and tyrosine residues in the N- and C-terminal portions of the repeat (Bruemmendorf and Rathjen, 1993). Using NMR techniques, the FNIII repeat structure has been shown to be composed of seven β-strands, forming two antiparallel β-sheets. An Arg-Gly-Asp (RGD) module within the FNIII domain conveys cell adhesive properties to a number of proteins (Main et al., 1992). Since the initial identification of the FNIII repeat in fibronectin, this domain has been found to be present in many animal and bacterial proteins, but has not been seen in plants or fungal proteins. In general, proteins containing FNIII domains can function as receptors or cell adhesion molecules. Proteins functioning as receptors include the insulin receptor family, the human growth hormone receptor, the erythropoietin receptor and several interleukin receptors. Fibronectin, tenascin and some members of the collagen family are cell surface proteins involved in cell adhesion (Bork and Doolittle, 1992, Marino-Buslje et al., 1998). Cell surface proteins containing FNIII repeats can influence neuronal development as shown for different members of the IgG-superfamily. Blocking the FNIII repeats of the neural cell adhesion molecule (NCAM) with a monoclonal antibody disturbed the axonal growth pattern and fasciculation in chicken retina (Pollerberg and Beck-Sickinger, 1993). Furthermore, expression studies and loss of function experiments on punc, a gene with a similar organization of FNIII and IgG domains, suggest a role in early development and in motor coordination (Salbaum, 1998, Yang et al., 2001). We now report the cloning and the analysis of expression and subcellular localization of two new genes that contain FNIII repeats and are members of a new gene family.

Section snippets

Cloning and sequencing

Frcp1 and Frcp2 fragments were subcloned from a BAC clone isolated from an arrayed mouse 129 genomic library (Incyte Genomics). By PCR (primers: 5′-GGATGTCAAGCGGATGCCAAGC-3′ and 5′-CACGAAGCCCAGGTCACAGC-3′), BAC 127H10 was identified to contain the genomic region for Frcp1. Frcp2 is encoded by BAC 217J06 (primers: 5′-AGAAGAAGGATGTGCGGATGCTCC-3′ and 5′-CTTGAAGAGCACAGGCTCACTGG-3′). Sequencing was performed by the Biopolymer Laboratory of the University of Maryland at Baltimore. Sequence analysis

cDNA structure, protein domains and genomic structure

The predicted $f$ ibronectin type III $r$ epeat $c$ ontaining $p$ rotein 1 (Frcp1) contains 219 amino acids with three identifiable domains (Fig. 1). An N-terminal signal peptide is formed by amino acids 1–30, followed by an 84-amino-acid fibronectin type III domain spanning amino acids 31–114. The final domain is a 22-amino-acid transmembrane domain from amino acid 151 to 172. The genomic region of Frcp1 spans 3.2 kb and was cloned in three overlapping fragments. The region was sequenced and the sequence

Conclusions

1.
We cloned, sequenced and analysed the expression of Frcp1 and Frcp2, two new fibronectin type III repeat containing genes.
2.
The two genes show high homologies in the fibronectin type III and transmembrane domains and no homology elsewhere or to other proteins, suggesting that these genes belong to a new subclass of fibronectin type III proteins.
3.
The strong expression of both members of the Frcp subfamily in embryonic brain and adult brain tissue suggests a role of these two genes during embryonic

Acknowledgements

A.T. is supported by the Alexander von Humboldt Foundation, Germany.

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Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes

Abstract

Introduction

Section snippets

Cloning and sequencing

cDNA structure, protein domains and genomic structure

Conclusions

Acknowledgements

Cell

FEBS Lett.

Dev. Biol.

Mech. Dev.

Pre-mRNA secondary structure and the regulation of splicing

Bioessays