Essential for cardiac morphogenesis. Binds DNA on E-box consensus sequence 5'-CANNTG-3' (By similarity). Plays an important role in limb development, particularly in the establishment of anterior-posterior polarization of the limb bud. Efficient DNA binding requires dimerization with another bHLH protein. At stages 8 to 9, expressed in the whole lateral plate mesoderm and precardiogenic mesoderm. At stage 10, expressed throughout the cardiac tube and the sinus venosus. By stage 15, expressed homogeneously in the various region of the heart, including the atria, future left ventricle, bulbus cordis and truncus arteriosus, and in the forming branchial arches. Expression persists through stage 20, but decreases thereafter. In the developing limbs, from the initiation of the buds (stages 16 to 17), expression is down-regulated at the anterior of the limb buds so that a gradient expression along the anterior-posterior axis of the bud is established with higher expression at the posterior border. At later stages, expression is restricted to the posterior border of the zeugopod and to the posterior autopod. In the autopod, dynamic expression of HAND2 affects the interdigital regions, the lateral borders of the digits and eventually the developing ventral tendons.