Hedgehog-interacting protein (HHIP)

Hedgehog-interacting protein (HHIP) is a highly conserved, secreted glycoprotein and the only known vertebrate-specific secreted antagonist of the Hedgehog (HH) signaling pathway. HHIP functions by binding with high affinity to all three mammalian HH ligands—Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Desert Hedgehog (DHH)—thereby sequestering them and preventing their interaction with the signaling receptor Patched 1 (PTCH1)[1][3][4][5][7]. Structurally, HHIP has multiple modules, including an N-terminal cysteine-rich domain (CRD), a glycosaminoglycan (GAG)-binding region, a central β-propeller, and EGF-like repeats. Regulation of HH signaling by HHIP is essential for proper embryonic development and tissue homeostasis; genetic variants of HHIP are associated with increased risk of chronic obstructive pulmonary disease and other disorders[1][3]. Downregulation or loss of HHIP expression contributes to HH pathway–dependent cancer and other pathologies[3][4].

Other names

HIPUNQ5825/PRO19644FLJ20992HHIP protein

Binds and sequesters Hedgehog ligands (Sonic Hedgehog [SHH], Indian Hedgehog [IHH], Desert Hedgehog [DHH]), acting as a **decoy receptor** and secreted inhibitor; prevents ligands from activating the canonical signaling receptor PTCH1[1][2][3][4][5][7].