RVxP motif is a protein motif involved in localizing proteins into cilia.

Cilia are sensory organelle of cells, whose malfunction can cause diseases such as polycystic kidney disease, ^[1] nephronophthisis and Bardet-Biedl syndrome. Proteins employed in the cilia are targeted there when they bear specific entry signals, whereas proteins not situated in cilia are removed or prevented from entering the organelles. ^[2] Entry signals have been found in ciliary/flagellar proteins of the protozoans Leishmania and Trypanosoma. ^[3]

The RVxP motif was first described for the PKD2 protein ^[4] and when inserted in the transferrin receptor it can target it to cilia. ^[5] It probably carries out its signal function through protein interactions ^[3] although the exact process ^[6] and where in the cell it takes place are unknown. ^[7] Three candidate proteins involved in "receiving" this signal are pericentrin at the basal body of cilia, intraflagellar transport proteins such as IFT57 ^[3] and ARF4 ^[8] while the BBSome does not appear to interact with the sequence. ^[9] The kinesins KIF17 is implicated in transporting the CNGB1 protein which has a RVxP motif into human cilia, ^[4] as is Rab8a in transporting PKD2. ^[5] Not all ciliary proteins use a RVxP motif for transport, however; ^[10] VxPx and Ax(S/A)xQ have also been described as cilium-targeting motifs. ^[6]

Examples of proteins with RVxP motifs associated with cilia:

• Mouse Ahi1, the homologue of human AHI1, fails to localize to cilia if its RVxP sequence is mutated. ^[11]
• Caenorhabditis elegans Arl13b requires a RVxP motif to localize to cilia, ^[12] a property shared by human ARL13B ^[13] but in the latter case a coiled-coil domain is also needed. ^[14]
• Human ATP1A4 has a motif similar to RVxP that may play a role in localizing the protein to sperm flagella. This sequence is conserved among species. ^[15]
• Human CNGB1 features a C-terminal RVxP motif at amino acids 821-824 which if mutated causes the protein to not reach the cilia; other factors however are also needed. ^[4] This motif is also found in animal CNGB1 homologues. ^[16]
• Human CRMP2 has a RVxP motif but it does not appear to be required for its ciliar trafficking. ^[17]
• Human FAM154A has a ciliary localization sequence. ^[18]
• Tetrahymena GEF1 has a ciliary localization sequence and mutating it causes the protein to no longer localize to cilia. ^[19]
• Human PDGFRA has a RVxP sequence and may localize to cilia thanks to it. ^[20]
• Human PKD2 trafficking into cilia has been found in vitro to rely on a N-terminal RVxP motif ^[21] as PKD2 mutants with alterations in this motif do not appear in cilia. ^[22] This motif is also found in animal PKD2 homologues ^[3] but not in Hydra. ^[23] Mutating this sequence in mice knocked out for PKD1 causes PKD2 to accumulate at the foot of the cilia. ^[19]

Other proteins associated with cilia for which the occurrence of a RVxP motif has been discussed are PKD1 and PSEN2. ^[24]