The Eukaryote Linear Motif resource for Functional Sites in Proteins
Functional site class:
Ciliary targeting motifs
Functional site description:
Ciliary transport is a specialised form of vesicular transport from the trans-Golgi network to the plasma membrane. It is responsible for the delivery of specialised membrane proteins like photoreceptors and ion channels to the cilia of vertebrate cells. Dysfunction in the delivery of ciliary cargo causes several human disorders (ciliopathies), such as retinal degeneration and polycystic kidneys.
ELMs with same func. site: TRG_Cilium_Arf4_1  TRG_Cilium_RVxP_2 
ELM Description:
The QVxPA$ ciliary targeting motif was identified in rhodopsin, as a patch of 5 conserved aminoacids in the C-terminal region. It permits the transport of the photoreceptor from the trans-Golgi network, to the outer segment of the rod retinal cells through mediation of the small GTPases of the Arf family.
Pattern: QV.P.$
Pattern Probability: 4.319e-07
Present in taxon: Vertebrata
Interaction Domain:
Arf (PF00025) ADP-ribosylation factor family (Stochiometry: 1 : 1)
o See 1 Instance for TRG_Cilium_Arf4_1
o Abstract
Cilia are hairlike cellular organelles with motile and sensory functions. They are assembled and maintained by intraflagellar transport (IFT), which uses microtubule-dependent motor proteins to mobilize ciliary cargo and to recycle components back to the basal body. Cilia compartmentalize receptors and signaling machinery, including effectors of phototransduction, olfaction, mechanosensation, as well as the crucial elements of signaling pathways (Inglis,2006). The vesicular trafficking required for the organization of the cilium is modulated by small GTPases of the Rab and Arf families (Jenkins,2007).
A ciliary targeting motif has been extensively characterised in rhodopsin. Mutations in the C-terminal region of rhodopsin were first related to severe forms of retinitis pigmentosa in humans (Berson,1996). Shortly afterwards, it was discovered that such mutations disrupted the conserved terminal motif QV[SA]PA and resulted in aberrant sub-cellular localisation of rhodopsin (Deretic,1998). Subsequently it was shown that sorting and delivery of rhodopsin to the rod outer segments is achieved by the interaction of its C-terminal motif with the GTPase activating protein Arf4 (Deretic,2005). The association of the active Arf4-GTP with the trans-Golgi network membrane depends on the VxPx motif. Budding of the rhodopsin transport carrier vesicle is regulated by the Arf GAP ASAP1. It couples proof-reading of cargo incorporation to vesicle budding through the GTP hydrolysis of Arf4-GTP. Additionally, ASAP1 functions as a scaffold that incorporates other proteins (FIP3 and Rab11) necessary for the liberation of the carrier vesicle and its subsequent delivery to the rod outer segment (Mazelova,2009).
A related ciliary targeting motif has been also identified in proteins like the cyclic nucleotide-gated channel subunit CNGB1b in olfactory neurons and polycystin-2 (PC2), a protein affected in polycystic kidney disease. While the involvement of the motif in the delivery of those proteins to the cilia of the respective cells has been experimentally verified (Geng,2006, Jenkins,2006), it is not yet clear if such transport requires Arf GTPases.
o 3 selected references:

o 10 GO-Terms:

o 1 Instance for TRG_Cilium_Arf4_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Protein NameGene NameStartEndSubsequenceLogic#Ev.OrganismNotes
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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