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Description

Rho GTPase-activating protein 36 (UniProt Q6ZRI8) is encoded by the ARHGAP36 gene (Gene ID 158763) in human. ARHGAP36 is a Rho GAP family member that acts as a potent hedgehog (Hh) pathway positive regulator. ARHGAP36 is reported to functionally associate with Hh pathway negative regulator Sufu (suppressor of fused) and ARHGAP36 overexpression results in reduced Gli3R levels, Gli2 ciliary accumulation, and Gli1 expression, in a Smo-independent manner. ARHGAP36 is produced with a signal peptide sequence (a.a. 1-40), which is removed posttranslationally to yield the mature protein with a Rho-GAP domain (a.a. 226-426). Unlike other Rho GAP domain-containing proteins, ARHGAP36 lacks the arginine finger motif that stimulates GTPase hydrolysis and GAP domain mutants can retain Gli-activating activity. ARHGAP36 isoforms are up-regulated in a subset of medulloblastomas, where they mediate noncanonical Gli activation by inhibiting Sufu.