Molecular cloning and characterization of human GIPC3, a novel gene homologous to human GIPC1 and GIPC2

Kermit is a Xenopus orthologue of human GIPC1/GIPC, which interacts with Frizzled-3 (FZD3) class of WNT receptor to modulate WNT signaling. GIPC1 interacts with TGFβ type III receptor to enhance TGFβ signaling. We have recently cloned and characterized a novel GIPC1-related gene, GIPC2. During isolation of GIPC2, we identified another novel GIPC1-related gene, GIPC3, by using bioinformatics. In this study, we isolated GIPC3 cDNAs from poly(A)+ RNA of human fetal lung. GIPC3 encoded a 312-amino-acid protein with a central PDZ domain, which showed 59.9% total-amino-acid identity with GIPC1, 55.3% total-amino-acid identity with GIPC2, and 57.2% total-amino-acid identity with Xenopus Kermit. GIPC3 gene on human chromosome 19p13.3 was found to consist of 6 exons, just like GIPC1 gene and GIPC2 gene. The 4.5-kb GIPC3 mRNA was almost ubiquitously expressed in normal adult tissues as well as in normal fetal tissues. Expression level of GIPC3 mRNA was relatively higher in jejunum, followed by lymph node, parietal lobe in brain, fetal spleen, and fetal thymus. GIPC3 mRNA was expressed in cervical cancer cell line HeLa S3, chronic myelogenous leukemia cell line K-562, and melanoma cell line G-361. GIPC3 mRNA was also expressed in gastric cancer cell lines TMK1 and MKN7; however, expression level of GIPC3 mRNA in TMK1 and MKN7 cells were significantly lower than that in normal stomach. This is the first report on molecular cloning of GIPC3, the third member of the GIPC gene family.