USP9X

USP9X
Identifiers
Aliases	USP9X, DFFRX, FAF, FAM, MRX99, MRXS99F, ubiquitin specific peptidase 9, X-linked, ubiquitin specific peptidase 9 X-linked, XLID99
External IDs	OMIM: 300072; MGI: 894681; HomoloGene: 3418; GeneCards: USP9X; OMA:USP9X - orthologs
Gene location (Human) Chr. X chromosome (human) Band Xp11.4 Start 41,085,445 bp End 41,236,579 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X A1.1|X 7.95 cM Start 12,937,737 bp End 13,039,567 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle frontal gyrus secondary oocyte paraflocculus of cerebellum Skeletal muscle tissue of rectus abdominis jejunum pars reticulata jejunal mucosa trabecular bone frontal pole lateral nuclear group of thalamus Top expressed in secondary oocyte genital tubercle zygote substantia nigra tail of embryo dentate gyrus of hippocampal formation granule cell pineal gland ventricular zone triceps brachii muscle primary visual cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cysteine-type peptidase activity co-SMAD binding peptidase activity protein binding cysteine-type endopeptidase activity hydrolase activity thiol-dependent deubiquitinase deubiquitinase activity Lys48-specific deubiquitinase activity Cellular component cytoplasm cytosol cell projection membrane growth cone Biological process female gamete generation ubiquitin-dependent protein catabolic process chromosome segregation neuron migration negative regulation of transcription by RNA polymerase II BMP signaling pathway proteolysis cell division axon extension cell cycle transforming growth factor beta receptor signaling pathway protein ubiquitination protein deubiquitination protein targeting to peroxisome regulation of circadian rhythm rhythmic process protein stabilization protein K48-linked deubiquitination protein deubiquitination involved in ubiquitin-dependent protein catabolic process positive regulation of DNA demethylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8239 22284 Ensembl ENSG00000124486 ENSMUSG00000031010 UniProt Q93008 P70398 RefSeq (mRNA) NM_001039590 NM_001039591 NM_004652 NM_021906 NM_009481 RefSeq (protein) NP_001034679 NP_001034680 NP_033507 Location (UCSC) Chr X: 41.09 – 41.24 Mb Chr X: 12.94 – 13.04 Mb PubMed search
Wikidata
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Probable ubiquitin carboxyl-terminal hydrolase FAF-X is an enzyme that in humans is encoded by the USP9X gene.

Function

This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation.

Depletion of USP9X from two-cell mouse embryos halts blastocyst development and results in slower blastomere cleavage rate, impaired cell adhesion and a loss of cell polarity. It has also been implicated that USP9X is likely to influence developmental processes through signaling pathways of Notch, Wnt, EGF, and mTOR. USP9X has been recognized in studies of mouse and human stem cells involving embryonic, neural and hematopoietic stem cells. High expression is retained in undifferentiated progenitor and stem cells and decreases as differentiation continues. USP9X is a protein-coding gene that has been implicated either directly through mutations or indirectly in a number of neurodevelopmental and neurodegenerative disorders. Three mutations have been connected with X-linked intellectual disability and disrupt neuronal growth and cell migration. Neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's disease, have also been linked to USP9X. Specifically, USP9X has been implicated in the regulation of the phosphorylation and expression of the microtule-associated protein tau, which forms pathological aggregates in Alzheimer's and other tauopathies. Scientists have generated a knockout model where they isolated hippocampal neurons from an USP9X-knockout male mouse, which showed a 43% reduction in axonal length and arborization compared to wildtype.

Interactions

USP9X has been shown to interact with:

• Beta-catenin,
• MARK4,
• MLLT4, and
• NUAK1.
• ERG.
• CEP131

Further reading

• D'Andrea A, Pellman D (1998). "Deubiquitinating enzymes: a new class of biological regulators". Crit. Rev. Biochem. Mol. Biol. 33 (5): 337–52. doi:10.1080/10409239891204251. PMID 9827704.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
• Noma T, Kanai Y, Kanai-Azuma M, Ishii M, Fujisawa M, Kurohmaru M, Kawakami H, Wood SA, Hayashi Y (2002). "Stage- and sex-dependent expressions of Usp9x, an X-linked mouse ortholog of Drosophila Fat facets, during gonadal development and oogenesis in mice". Gene Expr. Patterns. 2 (1–2): 87–91. doi:10.1016/S0925-4773(02)00290-3. PMID 12617843.
• Murray RZ, Jolly LA, Wood SA (2004). "The FAM deubiquitylating enzyme localizes to multiple points of protein trafficking in epithelia, where it associates with E-cadherin and beta-catenin". Mol. Biol. Cell. 15 (4): 1591–9. doi:10.1091/mbc.E03-08-0630. PMC 379258. PMID 14742711.
• Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
• Fu GK, Wang JT, Yang J, Au-Young J, Stuve LL (2004). "Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes". Genomics. 84 (1): 205–10. doi:10.1016/j.ygeno.2004.01.011. PMID 15203218.
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
• Al-Hakim AK, Göransson O, Deak M, Toth R, Campbell DG, Morrice NA, Prescott AR, Alessi DR (2005). "14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK". J. Cell Sci. 118 (Pt 23): 5661–73. doi:10.1242/jcs.02670. PMID 16306228.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
• Mouchantaf R, Azakir BA, McPherson PS, Millard SM, Wood SA, Angers A (2006). "The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X" (PDF). J. Biol. Chem. 281 (50): 38738–47. doi:10.1074/jbc.M605959200. PMID 17038327.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.