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Sonic Hedgehog Homolog (SHH) belongs to a three-protein family called Hedgehog. The other two family members are Indian Hedgehog (IHH) and Desert Hedgehog (DHH). Hedgehog proteins are key signaling molecules in embryonic development. SHH is expressed in various embryonic tissues and plays critical roles in regulating the patterning of many systems, such as limbs and brain. SHH also plays an important role in adult, including the division of adult stem cells and the development of certain cancers and other diseases. Human SHH is expressed as a 45kDa precursor, and undergoes a series of processing during secretion. After the removal of the signal peptide, a protease within the C-terminal domain catalyzes the cleavage of SHH into a 20 kDa N-terminal signaling domain (SHH-N) and a 25 kDa C-terminal domain (SHH-C). SHH-N has the “all signaling” capability. SHH-N binds to the 12 pass transmembrane protein Patched (Ptc) on cell surface, which releases the repression of the activity of Smoothened (Smo), a G-protein coupled receptor, by Ptc.