Heparin-binding EGF-like growth factor (HB-EGF) is a 12-16 kDa member of the epidermal growth factor (EGF) family. It possesses an EGF-like domain, and a heparin-binding motif. Mature HB-EGF is a soluble peptide that arises from proteolytic processing of the transmembrane form. Human HB-EGF shows 76% and 73% aa sequence identity with rat and mouse HB-EGF, respectively. It is required for normal cardiac valve formation and normal heart function, promotes smooth muscle cell proliferation. It may be involved in macrophage-mediated cellular proliferation; it is mitogenic for fibroblasts, but not endothelial cells. HB-EGF classified as a group 2 ErbB ligand based on its ability to activate both the EGF/ErbB1 and ErbB4 receptors. Activity associated with ErbB4 binding appears to be limited to non-mitogenic actions, while EGFR binding induces both mitogenic and non-mitogenic activity.