USP9X

Cilia effects upon perturbation of USP9X

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.49) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-2.58) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Human ciliopathy phenotype:

intellectual disability, X-linked 99, syndromic, female-restricted; intellectual disability, X-linked 99; X-linked non-syndromic intellectual disability

Subcellular localization

basal body, cilia, cytosol

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Reproduction & sperm
• Signaling (Hedgehog, GPCRs, ion channels)
• Transcription regulation

Function

Deubiquiti ting enzyme localised to centrosome, involved in context-dependent ciliogenesis. Regulates level of ubiquiti tion of NPHP5 to control ciliogenesis. In the G0/G1/S phase, USP9X is recruited to the centrosome by NPHP5, and later protects NPHP5 from ubiquiti tion, promoting cilia assembly. In the G2/M phase, USP9X dissociates from the centrosome allowing BBS11 to K63 ubiquiti te NPHP5, triggering loss of cilia. Works with two E3 ubiquitin ligases BBS11/TRIM32 and MARCHF7 (28498859). Binds and stabilises PCM1 to prevent its degradation and regulate centriolar satellite integrity. Regulates centrosome duplication (30584065). During Serum- Starvation-Induced Ciliogenesis, it is recruited by SNX17 to antagonize MIB1- Mediated Ubiquiti tion and Degradation of PCM1 (31671755).