IQGAP1 - Domains

Domains

IQGAP1 is a 190 kDa protein with 5 domains. A protein domain is a subsection of a protein that shows up multiple times in biology and can exist independently of the surrounding protein. It is very similar to subsections of other proteins, and could be cut out of the current protein, exist and function by itself, or be pasted in to a new protein strand and still function properly. Since this area of the protein is conserved in amino acid sequence and structure, it can be characterized by function or binding partner. IQGAP1 has 5 well-known domains separated by other amino acids.

Starting at the N-terminus (or front of the protein), IQGAP1 contains a calponin homology domain (CHD), which mediates actin-binding and binds calponin.

The WW, or poly-proline protein-protein domain, so named because of two functionally conserved tryptophans, W, is a protein-protein interaction domain that associates with proline-rich regions of other proteins.

The WW domain is followed by 4 IQ motifs which form an IQ domain. This domain binds calmodulin, a protein known as a calcium sensor that can bind and regulate many target proteins.

A GRD (rasGAP-related domain) follows the IQ domain. This domain is highly similar to the functional subunit of Ras GTPase-activating proteins (GAPs) and was thus thought to have GAP function. IQGAP1 does bind Rho GTPases CDC42 and RAC1, however, IQGAP1 is unusual in that it actually has no GAP function, and instead stabilizes the GTP-bound proteins in their active state.

Finally, IQGAP1 has a RasGAP_c carboxy terminal sequence important for binding Beta-catenin and E-cadherin.