ADP-ribosylation factor-like protein 3

Definition:

Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). Required for normal cytokinesis and cilia signaling. Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms. Required for targeting proteins to the cilium, including myristoylated NPHP3 and prenylated INPP5E. Targets NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium. Required for PKD1:PKD2 complex targeting from the trans-Golgi network to the cilium (By similarity).

References:

[1]. Chengjing Zhou, et al. Arl2 and Arl3 regulate different microtubule-dependent processes. Mol Biol Cell. 2006 May;17(5):2476-87. [Content Brief]

[2]. Kevin J Wright, et al. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 2011 Nov 15;25(22):2347-60. [Content Brief]

[3]. Stefan Veltel, et al. Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex. FEBS Lett. 2008 Jul 23;582(17):2501-7. [Content Brief]

[4]. Sumaya Alkanderi, et al. ARL3 Mutations Cause Joubert Syndrome by Disrupting Ciliary Protein Composition. Am J Hum Genet. 2018 Oct 4;103(4):612-620. [Content Brief]

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