SMO

G protein-coupled receptor, which transduces the smoothened signaling pathway. Activated by cholesterol in response to hedgehog (DHH, IHH or SHH) morphogens. In absence of hedgehog, SMO is inactivated by patched protein (PTCH1 or PTCH2), which prevents SMO access to cholesterol. In response to hedgehog-binding to pathched, inhibition is relieved, promoting SMO translocation to primary cilium and activation by cholesterol: cholesterol causes a conformation change that triggers signaling via G protein G(i), mediating inhibition of adenylate cyclase activity and decreassed production of cAMP. Decreased cAMP levels then inhibit protein kinase A (PKA) and promote release of GLI (GLI1, GLI2 and GLI3) transcription factors, which activate expression of target genes. Active SMO also directly inhibits PKA by sequestering its catalytic subunit, PRKACA, at the cell membrane, preventing PRKACA-mediated phosphorylation and subsequent processing of GLI transcription factors. Active SMO also promotes the removal of GPR161, a key inhibitor of the smoothened signaling pathway, from primary cilia (By similarity)..

Function from UniProtKB (Q99835), read 2026-09-23. CC BY 4.0.