Molecular cloning and characterization of human GIPC2, a novel gene homologous to human GIPC1 and Xenopus Kermit

PDZ-domain protein GIPC1/GIPC interacts with GTPase-activating protein RGS-GAIP, TGFbeta type III receptor, and integrin alpha6A subunit. Kermit, a Xenopus orthologue of human GIPC1, interacts with some class of WNT receptor. In this study, we identified a novel GIPC1-related gene in human genome by using bioinformatics, and isolated GIPC2 cDNAs by using cDNA-PCR. GIPC2 encoded a 315-amino-acid protein with a central PDZ domain, which showed 62.0% total-amino-acid identity with GIPC1. Both GIPC2 gene on human chromosome 1 and GIPC1 gene on human chromosome 19p13.1 were found to consist of 6 exons. Exon-intron structures of GIPC2 gene and GIPC1 gene were well conserved. GIPC2 mRNA was relatively highly expressed in ascending colon, followed by kidney and pancreas. Among 3.7-, 2.6-, and 1.7-kb GIPC2 mRNAs generated due to alternative polyadenylation, 2.6-kb GIPC2 mRNA was the major GIPC2 transcript in adult kidney. Expression of GIPC2 mRNA was significantly down-regulated in 6 out of 14 cases of primary kidney tumors, in 5 out of 11 cases of primary colon tumors, and in 1 out of 7 cases of primary rectal tumors. Because GIPC2 might bind to TGFbeta type III receptor or some class of WNT receptor, just like GIPC1 or Kermit, down-regulation of GIPC2 mRNA in human primary tumors might lead to interference of TGFbeta signaling or some class of WNT signaling. This is the first report on molecular cloning of GIPC2, the second member of the GIPC gene family, which is down-regulated in human primary kidney and colorectal tumors.