A novel RasGAP-related protein, designated IQGAP1 was cloned in 1994 by RNA-PCR from metastatic human osteosarcoma tissue. Subsequent investigation revealed a family of IQGAP proteins. Human IQGAP2 has been identified and recently a putative IQGAP3 was found in the human genome. In addition, IQGAP homologues have been described in Hydra, C. elegans and yeast. The high level of conservation implies that IQGAP proteins participate in fundamental cellular processes.

IQGAP1 contains several protein-interacting domains which mediate binding to diverse target molecules. These targets include actin, calmodulin, S100B, essential light chains (ELC), Cdc42, Rac1, E-cadherin, ß-catenin and CLIP-170. Binding induces functional sequelae and IQGAP1 enhances F-actin polymerization in vitro, activates Cdc42 and Rac, reduces E-cadherin-mediated cell-cell adhesion, enhances ß-catenin transcriptional coactivation and captures growing microtubules. Moreover, binding of one protein alters the ability of IQGAP1 to interact with other proteins. For example, calmodulin reduces IQGAP1 binding to actin, Cdc42, E-cadherin and ß-catenin. The heterogeneity of IQGAP1 targets suggests that IQGAP1 functions as a scaffolding protein that can assemble multiprotein complexes and integrate signaling pathways. This hypothesis is supported by evidence from several groups who have documented that IQGAP1 can bind several proteins simultaneously.