Identification of LRRC4, a novel member of leucine-rich repeat (LRR) superfamily, and its expression analysis in brain tumor

In order to clone novel gene associated with tumor in human chromosome 7q31-32 harboring one or more tumor suppressor gene, expressed sequence tag (EST) -mediated positional cloning strategy was used and a novel human brain cDNA was identified. The isolated cDNA encodes a polypeptide of 653 amino acids with a theoretical molecular mass of 72.7 ku and a calculated isoelectric point of 6.58. The deduced amino acids contains seven typical leucine-rich repeats (LRRs) flanked by N- and C-terminal cysteine-rich LRR region, one immunoglobulin C2 like domain, one signal peptide at N-terminal and one transmembrane region at C-terminal. Amino acid sequence of this novel gene exhibits high similarity and similar domain organization as many other LRR proteins. Analysis of this novel gene shows no significant homology to any reported genes in database of GenBank. So it is a novel member of leucine-rich repeat superfamily and designated as LRRC4 according to the guide of HUGO Gene Nomenclature Committee (GenBank Accession No. AF196976). Northern Blot and RTPCR analysis revealed that normal expression of LRRC4 was highly specific for brain, whereas absent or significantly down-regulated in primary brain tumors including glioma, meningioma and pituitary adenoma. In addition, mouse homology of LRRC4 has been mapped to mouse chromosome 6 by similarity analysis (GenBank Accession No. AF290542). Taking the structural properties and expression patterns into consideration, LRRC4 may play an important role in nervous system.