ARL6

ARL6 (BBS3) is a 186-residue ADP-ribosylation factor-like small GTPase of the Arf family within the Ras superfamily. Like canonical Arf/Sar1 GTPases it cycles between an inactive GDP-bound and an active GTP-bound state; GTP loading exposes an N-terminal amphipathic helix that inserts into membranes, so the GTP-bound form is peripherally associated with the cytoplasmic face of the ciliary membrane. The defining activity of ARL6 is to act as the membrane-targeting switch for the BBSome, an octameric Bardet-Biedl syndrome protein complex that functions as a coat sorting membrane proteins into and out of primary cilia. ARL6 is not itself a structural subunit of the BBSome; rather, GTP-bound ARL6 binds the BBS1 beta-propeller and recruits the BBSome onto the ciliary membrane, where it nucleates polymerization of the BBSome coat. Through this activity ARL6 controls ciliary trafficking of signaling receptors (e.g. SSTR3, MCHR1, Smoothened) and contributes to Hedgehog and Wnt signaling. ARL6 localizes to the primary cilium, concentrating in a ring at the distal basal body near the ciliary gate and in membrane-associated patches flanking the axoneme. The intraflagellar transport protein IFT27/RABL4 binds nucleotide-free ARL6 to promote its activation and BBSome exit from cilia. Loss-of-function mutations that impair GTP binding cause Bardet-Biedl syndrome type 3 and retinitis pigmentosa 55.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

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• bbsome_trafficking via Bardet-Biedl syndrome, BBSome-related retinitis pigmentosa