ID USP9X_HUMAN Reviewed; 2554 AA. AC Q93008; O75550; Q8WWT3; Q8WX12; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 07-OCT-2020, sequence version 4. DT 10-JUN-2026, entry version 233. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 9X; DE EC=3.4.19.12 {ECO:0000269|PubMed:18254724, ECO:0000269|PubMed:19135894, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:29626158, ECO:0000269|PubMed:30914461, ECO:0000269|PubMed:37454738}; DE AltName: Full=Deubiquitinating enzyme FAF-X; DE AltName: Full=Fat facets in mammals; DE Short=hFAM; DE AltName: Full=Fat facets protein-related, X-linked; DE AltName: Full=Ubiquitin thioesterase FAF-X; DE AltName: Full=Ubiquitin-specific protease 9, X chromosome; DE AltName: Full=Ubiquitin-specific-processing protease FAF-X; GN Name=USP9X {ECO:0000303|PubMed:18254724, ECO:0000312|HGNC:HGNC:12632}; GN Synonyms=DFFRX, FAM, USP9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain, Retina, and Testis; RX PubMed=8922996; DOI=10.1093/hmg/5.11.1695; RA Jones M.H., Furlong R.A., Burkin H., Chalmers I.J., Brown G.M., Khwaja O., RA Affara N.A.; RT "The Drosophila developmental gene fat facets has a human homologue in RT Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2."; RL Hum. Mol. Genet. 5:1695-1701(1996). RN [2] RP ERRATUM OF PUBMED:8922996. RA Jones M.H., Furlong R.A., Burkin H., Chalmers I.J., Brown G.M., Khwaja O., RA Affara N.A.; RL Hum. Mol. Genet. 6:334-335(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2226-2554 (ISOFORM 2). RC TISSUE=Brain; RA Yu W., Gibbs R.A.; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-2540, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [6] RP FUNCTION, AND INTERACTION WITH BIRC5. RX PubMed=16322459; DOI=10.1126/science.1120160; RA Vong Q.P., Cao K., Li H.Y., Iglesias P.A., Zheng Y.; RT "Chromosome alignment and segregation regulated by ubiquitination of RT survivin."; RL Science 310:1499-1504(2005). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1600, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2547, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2443, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17693683; DOI=10.1074/mcp.m700120-mcp200; RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., RA Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.; RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling RT network: indicating the involvement of ribonucleoside-diphosphate reductase RT M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal RT transduction."; RL Mol. Cell. Proteomics 6:1952-1967(2007). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH MARK4 AND NUAK1. RX PubMed=18254724; DOI=10.1042/bj20080067; RA Al-Hakim A.K., Zagorska A., Chapman L., Deak M., Peggie M., Alessi D.R.; RT "Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)- RT linked polyubiquitin chains."; RL Biochem. J. 411:249-260(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1600, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1600; SER-2443 AND SER-2547, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SMAD4, AND SUBCELLULAR RP LOCATION. RX PubMed=19135894; DOI=10.1016/j.cell.2008.10.051; RA Dupont S., Mamidi A., Cordenonsi M., Montagner M., Zacchigna L., Adorno M., RA Martello G., Stinchfield M.J., Soligo S., Morsut L., Inui M., Moro S., RA Modena N., Argenton F., Newfeld S.J., Piccolo S.; RT "FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, RT controls Smad4 monoubiquitination."; RL Cell 136:123-135(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1600, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2547 AND THR-2551, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1600 AND SER-2443, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588; THR-590; SER-1600; RP SER-2443 AND SER-2547, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP INTERACTION WITH OTUD4; ALKBH3 AND USP7, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25944111; DOI=10.15252/embj.201490497; RA Zhao Y., Majid M.C., Soll J.M., Brickner J.R., Dango S., Mosammaparast N.; RT "Noncanonical regulation of alkylation damage resistance by the OTUD4 RT deubiquitinase."; RL EMBO J. 34:1687-1703(2015). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=22371489; DOI=10.1074/jbc.m112.340158; RA Grou C.P., Francisco T., Rodrigues T.A., Freitas M.O., Pinto M.P., RA Carvalho A.F., Domingues P., Wood S.A., Rodriguez-Borges J.E., RA Sa-Miranda C., Fransen M., Azevedo J.E.; RT "Identification of ubiquitin-specific protease 9X (USP9X) as a RT deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate."; RL J. Biol. Chem. 287:12815-12827(2012). RN [23] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=26598551; DOI=10.15252/embr.201540809; RA Kim M., Kim M., Park S.J., Lee C., Lim D.S.; RT "Role of Angiomotin-like 2 mono-ubiquitination on YAP inhibition."; RL EMBO Rep. 17:64-78(2016). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=29626158; DOI=10.1042/bcj20180005; RA Zhang Y., Duan C., Yang J., Chen S., Liu Q., Zhou L., Huang Z., Xu Y., RA Xu G.; RT "Deubiquitinating enzyme USP9X regulates cellular clock function by RT modulating the ubiquitination and degradation of a core circadian protein RT BMAL1."; RL Biochem. J. 475:1507-1522(2018). RN [25] RP FUNCTION, INDUCTION, AND MUTAGENESIS OF CYS-1566. RX PubMed=33378666; DOI=10.1016/j.celrep.2020.108564; RA Wrobel L., Siddiqi F.H., Hill S.M., Son S.M., Karabiyik C., Kim H., RA Rubinsztein D.C.; RT "mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of RT RICTOR."; RL Cell Rep. 33:108564-108564(2020). RN [26] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=34404733; DOI=10.26508/lsa.202000953; RA Hwang D., Kim M., Kim S., Kwon M.R., Kang Y.S., Kim D., Kang H.C., RA Lim D.S.; RT "AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by RT facilitating LATS activation."; RL Life. Sci Alliance 4:0-0(2021). RN [27] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=37454738; DOI=10.1016/j.jbc.2023.105055; RA Wang P., Wang J., Yao S., Cui M., Cheng Y., Liu W., Gao Z., Hu J., RA Zhang J., Zhang H.; RT "Deubiquitinase USP9X stabilizes RNA m6A demethylase ALKBH5 and promotes RT acute myeloid leukemia cell survival."; RL J. Biol. Chem. 299:105055-105055(2023). RN [28] RP INVOLVEMENT IN XLID99, VARIANTS XLID99 HIS-2093 AND ILE-2157, RP CHARACTERIZATION OF VARIANTS XLID99 HIS-2093 AND ILE-2157, FUNCTION, RP INTERACTION WITH DCX, AND SUBCELLULAR LOCATION. RX PubMed=24607389; DOI=10.1016/j.ajhg.2014.02.004; RA Homan C.C., Kumar R., Nguyen L.S., Haan E., Raymond F.L., Abidi F., RA Raynaud M., Schwartz C.E., Wood S.A., Gecz J., Jolly L.A.; RT "Mutations in USP9X are associated with X-linked intellectual disability RT and disrupt neuronal cell migration and growth."; RL Am. J. Hum. Genet. 94:470-478(2014). RN [29] RP INVOLVEMENT IN MRXS99F, SUBCELLULAR LOCATION, VARIANTS MRXS99F RP 371-ARG--GLN-2554 DEL; 852-ARG--GLN-2554 DEL; 1255-GLN--GLN-2554 DEL; RP 1268-TYR--GLN-2554 DEL; 2483-ASP--GLU-2487 DEL AND TRP-1693, AND RP CHARACTERIZATION OF VARIANT MRXS99F 852-ARG--GLN-2554 DEL. RX PubMed=26833328; DOI=10.1016/j.ajhg.2015.12.015; RA Reijnders M.R., Zachariadis V., Latour B., Jolly L., Mancini G.M., RA Pfundt R., Wu K.M., van Ravenswaaij-Arts C.M., Veenstra-Knol H.E., RA Anderlid B.M., Wood S.A., Cheung S.W., Barnicoat A., Probst F., RA Magoulas P., Brooks A.S., Malmgren H., Harila-Saari A., Marcelis C.M., RA Vreeburg M., Hobson E., Sutton V.R., Stark Z., Vogt J., Cooper N., RA Lim J.Y., Price S., Lai A.H., Domingo D., Reversade B., Gecz J., RA Gilissen C., Brunner H.G., Kini U., Roepman R., Nordgren A., Kleefstra T.; RT "De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific RT Recognizable Syndrome with Developmental Delay and Congenital RT Malformations."; RL Am. J. Hum. Genet. 98:373-381(2016). RN [30] {ECO:0007744|PDB:5WCH} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1551-1970 IN COMPLEX WITH ZINC, RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-1566; RP CYS-1727 AND HIS-1729. RX PubMed=30914461; DOI=10.1073/pnas.1815027116; RA Paudel P., Zhang Q., Leung C., Greenberg H.C., Guo Y., Chern Y.H., Dong A., RA Li Y., Vedadi M., Zhuang Z., Tong Y.; RT "Crystal structure and activity-based labeling reveal the mechanisms for RT linkage-specific substrate recognition by deubiquitinase USP9X."; RL Proc. Natl. Acad. Sci. U.S.A. 116:7288-7297(2019). CC -!- FUNCTION: Deubiquitinase involved both in the processing of ubiquitin CC precursors and of ubiquitinated proteins (PubMed:18254724, CC PubMed:19135894, PubMed:22371489, PubMed:25944111, PubMed:29626158, CC PubMed:30914461, PubMed:37454738). May therefore play an important CC regulatory role at the level of protein turnover by preventing CC degradation of proteins through the removal of conjugated ubiquitin CC (PubMed:18254724, PubMed:19135894, PubMed:22371489, PubMed:25944111, CC PubMed:29626158, PubMed:30914461, PubMed:37454738). Specifically CC hydrolyzes 'Lys-11'-, followed by 'Lys-63'-, 'Lys-48'- and 'Lys-6'- CC linked polyubiquitins chains (PubMed:30914461). Essential component of CC TGF-beta/BMP signaling cascade (PubMed:19135894). Specifically CC deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 CC ubiquitin-protein ligase TRIM33 (PubMed:19135894). Deubiquitinates CC alkylation repair enzyme ALKBH3 (PubMed:25944111). OTUD4 recruits USP7 CC and USP9X to stabilize ALKBH3, thereby promoting the repair of CC alkylated DNA lesions (PubMed:25944111). Deubiquitinates RNA CC demethylase enzyme ALKBH5, promoting its stability (PubMed:37454738). CC Deubiquitinates mTORC2 complex component RICTOR at 'Lys-294' by CC removing 'Lys-63'-linked polyubiquitin chains, stabilizing RICTOR and CC enhancing its binding to MTOR, thus promoting mTORC2 complex assembly CC (PubMed:33378666). Regulates chromosome alignment and segregation in CC mitosis by regulating the localization of BIRC5/survivin to mitotic CC centromeres (PubMed:16322459). Involved in axonal growth and neuronal CC cell migration (PubMed:24607389). Regulates cellular clock function by CC enhancing the protein stability and transcriptional activity of the CC core circadian protein BMAL1 via its deubiquitinating activity CC (PubMed:29626158). Acts as a regulator of peroxisome import by CC mediating deubiquitination of PEX5: specifically deubiquitinates PEX5 CC monoubiquitinated at 'Cys-11' following its retrotranslocation into the CC cytosol, resetting PEX5 for a subsequent import cycle CC (PubMed:22371489). Deubiquitinates PEG10 (By similarity). Inhibits the CC activation of the Hippo signaling pathway via deubiquitination of CC AMOTL2 at 'Lys-347' and 'Lys-408' which prohibits its interaction with CC and activation of LATS2. Loss of LATS2 activation and subsequent loss CC of YAP1 phosphorylation results in an increase in YAP1-driven CC transcription of target genes (PubMed:26598551, PubMed:34404733). CC {ECO:0000250|UniProtKB:P70398, ECO:0000269|PubMed:16322459, CC ECO:0000269|PubMed:18254724, ECO:0000269|PubMed:19135894, CC ECO:0000269|PubMed:22371489, ECO:0000269|PubMed:24607389, CC ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26598551, CC ECO:0000269|PubMed:29626158, ECO:0000269|PubMed:30914461, CC ECO:0000269|PubMed:33378666, ECO:0000269|PubMed:34404733, CC ECO:0000269|PubMed:37454738}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:18254724, CC ECO:0000269|PubMed:19135894, ECO:0000269|PubMed:22371489, CC ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26598551, CC ECO:0000269|PubMed:29626158, ECO:0000269|PubMed:30914461, CC ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:37454738}; CC -!- SUBUNIT: Interacts with SMAD4, MARK4, NUAK1 and BIRC5/survivin CC (PubMed:16322459, PubMed:18254724, PubMed:19135894). Interacts with DCX CC (PubMed:24607389). Interacts with OTUD4 and USP7; the interaction is CC direct (PubMed:25944111). {ECO:0000269|PubMed:16322459, CC ECO:0000269|PubMed:18254724, ECO:0000269|PubMed:19135894, CC ECO:0000269|PubMed:24607389, ECO:0000269|PubMed:25944111}. CC -!- INTERACTION: CC Q93008; P42858: HTT; NbExp=8; IntAct=EBI-302524, EBI-466029; CC Q93008; Q07820: MCL1; NbExp=10; IntAct=EBI-302524, EBI-1003422; CC Q93008; O60285: NUAK1; NbExp=2; IntAct=EBI-302524, EBI-1046789; CC Q93008; Q13485: SMAD4; NbExp=2; IntAct=EBI-302524, EBI-347263; CC Q93008; P40337: VHL; NbExp=5; IntAct=EBI-302524, EBI-301246; CC Q93008; P08393: ICP0; Xeno; NbExp=3; IntAct=EBI-302524, EBI-6148881; CC Q93008; P0DTC9: N; Xeno; NbExp=3; IntAct=EBI-302524, EBI-25475856; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19135894, CC ECO:0000269|PubMed:26833328}. Cell projection, growth cone CC {ECO:0000269|PubMed:24607389}. Cytoplasm, cytoskeleton, cilium axoneme CC {ECO:0000269|PubMed:26833328}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Short; CC IsoId=Q93008-1; Sequence=Displayed; CC Name=2; Synonyms=Long; CC IsoId=Q93008-3; Sequence=VSP_060711; CC -!- TISSUE SPECIFICITY: Widely expressed in embryonic and adult tissues. CC {ECO:0000269|PubMed:8922996}. CC -!- INDUCTION: By growth factors. {ECO:0000269|PubMed:33378666}. CC -!- DISEASE: Intellectual developmental disorder, X-linked 99 (XLID99) CC [MIM:300919]: A disorder characterized by significantly below average CC general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. CC Intellectual deficiency is the only primary symptom of non-syndromic X- CC linked forms, while syndromic forms present with associated physical, CC neurological and/or psychiatric manifestations. CC {ECO:0000269|PubMed:24607389}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Intellectual developmental disorder, X-linked 99, syndromic, CC female-restricted (MRXS99F) [MIM:300968]: A form of intellectual CC disability, a disorder characterized by significantly below average CC general intellectual functioning, associated with impairments in CC adaptive behavior and manifested during the developmental period. CC MRXS99F affected females manifest intellectual disability, CC developmental delay, facial dysmorphism, short stature, and distinct CC congenital malformations comprising choanal atresia, anal CC abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft CC palate/bifid uvula, progressive scoliosis, and structural brain CC abnormalities. Inheritance is X-linked dominant. CC {ECO:0000269|PubMed:26833328}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Escapes X-inactivation. {ECO:0000269|PubMed:8922996}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X98296; CAA66942.1; -; mRNA. DR EMBL; AL109797; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391259; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF070645; AAC25395.1; -; mRNA. DR CCDS; CCDS43930.1; -. [Q93008-3] DR CCDS; CCDS55403.1; -. [Q93008-1] DR RefSeq; NP_001034679.2; NM_001039590.3. [Q93008-3] DR RefSeq; NP_001034680.2; NM_001039591.3. [Q93008-1] DR RefSeq; XP_047298504.1; XM_047442548.1. [Q93008-3] DR RefSeq; XP_047298506.1; XM_047442550.1. [Q93008-1] DR RefSeq; XP_054183907.1; XM_054327932.1. [Q93008-3] DR RefSeq; XP_054183909.1; XM_054327934.1. [Q93008-1] DR PDB; 5VBD; X-ray; 1.50 A; A=880-970. DR PDB; 5WCH; X-ray; 2.50 A; A/B/C/D=1551-1970. DR PDB; 7YXX; EM; 3.30 A; A/B/C=1-2554. DR PDB; 7YXY; EM; 3.10 A; A=1-2554. DR PDBsum; 5VBD; -. DR PDBsum; 5WCH; -. DR PDBsum; 7YXX; -. DR PDBsum; 7YXY; -. DR AlphaFoldDB; Q93008; -. DR EMDB; EMD-14368; -. DR EMDB; EMD-14369; -. DR SMR; Q93008; -. DR BioGRID; 113867; 473. DR CORUM; Q93008; -. DR DIP; DIP-27562N; -. DR FunCoup; Q93008; 4328. DR IntAct; Q93008; 169. DR MINT; Q93008; -. DR NDEx; IQUERY-CP-USP9X; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000316357; -. DR BindingDB; Q93008; -. DR ChEMBL; CHEMBL2406899; -. DR MEROPS; C19.017; -. DR GlyGen; Q93008; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q93008; -. DR MetOSite; Q93008; -. DR PhosphoSitePlus; Q93008; -. DR SwissPalm; Q93008; -. DR BioMuta; USP9X; -. DR DMDM; 317373496; -. DR jPOST; Q93008; -. DR MassIVE; Q93008; -. DR PaxDb; 9606-ENSP00000316357; -. DR PeptideAtlas; Q93008; -. DR ProteomicsDB; 75667; -. [Q93008-3] DR ProteomicsDB; 75668; -. [Q93008-1] DR Pumba; Q93008; -. DR Antibodypedia; 25013; 383 antibodies from 34 providers. DR DNASU; 8239; -. DR Ensembl; ENST00000324545.9; ENSP00000316357.6; ENSG00000124486.16. [Q93008-3] DR Ensembl; ENST00000378308.7; ENSP00000367558.2; ENSG00000124486.16. [Q93008-1] DR Ensembl; ENST00000704650.1; ENSP00000515975.1; ENSG00000124486.16. [Q93008-1] DR Ensembl; ENST00000929529.1; ENSP00000599588.1; ENSG00000124486.16. [Q93008-1] DR Ensembl; ENST00000971820.1; ENSP00000641879.1; ENSG00000124486.16. [Q93008-1] DR GeneID; 8239; -. DR KEGG; hsa:8239; -. DR MANE-Select; ENST00000378308.7; ENSP00000367558.2; NM_001039591.3; NP_001034680.2. DR UCSC; uc004dfb.3; human. [Q93008-1] DR AGR; HGNC:12632; -. DR ClinPGx; PA37257; -. DR CTD; 8239; -. DR DisGeNET; 8239; -. DR GeneCards; USP9X; -. DR HGNC; HGNC:12632; USP9X. DR HPA; ENSG00000124486; Low tissue specificity. DR MalaCards; USP9X; -. DR MIM; 300072; gene. DR MIM; 300919; phenotype. DR MIM; 300968; phenotype. DR OpenTargets; ENSG00000124486; -. DR Orphanet; 480880; X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability. DR Orphanet; 777; X-linked non-syndromic intellectual disability. DR VEuPathDB; HostDB:ENSG00000124486; -. DR eggNOG; KOG1866; Eukaryota. DR GeneTree; ENSGT00940000155375; -. DR HOGENOM; CLU_000331_1_0_1; -. DR InParanoid; Q93008; -. DR OMA; YDYEREC; -. DR OrthoDB; 289038at2759; -. DR PAN-GO; Q93008; 5 GO annotations based on evolutionary models. DR PhylomeDB; Q93008; -. DR PathwayCommons; Q93008; -. DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes. DR Reactome; R-HSA-9013420; RHOU GTPase cycle. DR Reactome; R-HSA-9013424; RHOV GTPase cycle. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR SignaLink; Q93008; -. DR SIGNOR; Q93008; -. DR Agora; ENSG00000124486; -. DR BioGRID-ORCS; 8239; 86 hits in 804 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; USP9X; human. DR GeneWiki; USP9X; -. DR GenomeRNAi; 8239; -. DR Pharos; Q93008; Tbio. DR PRO; PR:Q93008; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q93008; protein. DR Bgee; ENSG00000124486; Expressed in endometrium epithelium and 212 other cell types or tissues. DR ExpressionAtlas; Q93008; baseline and differential. DR GO; GO:0005930; C:axoneme; IEA:UniProtKB-SubCell. DR GO; GO:0005813; C:centrosome; IDA:UniProt. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0070410; F:co-SMAD binding; IPI:BHF-UCL. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB. DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:Reactome. DR GO; GO:0101005; F:deubiquitinase activity; IDA:UniProt. DR GO; GO:0180017; F:K11-linked deubiquitinase activity; IDA:UniProtKB. DR GO; GO:1990380; F:K48-linked deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0061578; F:K63-linked deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0140313; F:molecular sequestering activity; IDA:UniProt. DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome. DR GO; GO:0048675; P:axon extension; IMP:UniProtKB. DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW. DR GO; GO:0060271; P:cilium assembly; IDA:UniProt. DR GO; GO:0061824; P:cytosolic ciliogenesis; IDA:UniProt. DR GO; GO:0006307; P:DNA alkylation repair; IDA:UniProtKB. DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc. DR GO; GO:0008104; P:intracellular protein localization; TAS:Reactome. DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; IDA:UniProtKB. DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:Reactome. DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB. DR GO; GO:0032092; P:positive regulation of protein binding; IMP:UniProtKB. DR GO; GO:1904515; P:positive regulation of TORC2 signaling; IDA:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0071947; P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0016562; P:protein import into peroxisome matrix, receptor recycling; IDA:UniProtKB. DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IBA:GO_Central. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB. DR CDD; cd02659; peptidase_C19C; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR056850; ARM_UBP34_24_USP9X_Y. DR InterPro; IPR021905; DUF3517. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR050164; Peptidase_C19. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR055176; UBP24/USP9X/USP9Y_UBL. DR InterPro; IPR028889; USP. DR InterPro; IPR018200; USP_CS. DR PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR24006:SF925; UBIQUITINYL HYDROLASE 1; 1. DR Pfam; PF25010; ARM_UBP24_USP9X-Y; 1. DR Pfam; PF12030; DUF3517; 1. DR Pfam; PF00443; UCH; 1. DR Pfam; PF22900; UCH_UBL1; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Biological rhythms; Cell cycle; KW Cell division; Cell projection; Chromosome partition; Cytoplasm; KW Cytoskeleton; Disease variant; Hydrolase; Intellectual disability; Mitosis; KW Phosphoprotein; Protease; Proteomics identification; Reference proteome; KW Thiol protease; Ubl conjugation pathway; Zinc. FT CHAIN 1..2554 FT /note="Ubiquitin carboxyl-terminal hydrolase 9X" FT /id="PRO_0000080689" FT DOMAIN 1557..1956 FT /note="USP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035" FT REGION 1..65 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 967..999 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1592..1621 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2475..2554 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..44 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 969..989 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1601..1617 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2475..2484 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2503..2513 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2527..2537 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1566 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093, FT ECO:0000305|PubMed:30914461" FT ACT_SITE 1879 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT BINDING 1727 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:30914461, FT ECO:0007744|PDB:5WCH" FT BINDING 1729 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:30914461, FT ECO:0007744|PDB:5WCH" FT BINDING 1771 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:30914461, FT ECO:0007744|PDB:5WCH" FT BINDING 1774 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:30914461, FT ECO:0007744|PDB:5WCH" FT MOD_RES 588 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 590 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1600 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2443 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17693683, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2540 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 2547 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2551 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT VAR_SEQ 2477 FT /note="E -> EVKKATSVQQIEMEESK (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_060711" FT VARIANT 371..2554 FT /note="Missing (in MRXS99F; dbSNP:rs869025592)" FT /evidence="ECO:0000269|PubMed:26833328" FT /id="VAR_086077" FT VARIANT 852..2554 FT /note="Missing (in MRXS99F; decreased expression levels; FT dbSNP:rs869025588)" FT /evidence="ECO:0000269|PubMed:26833328" FT /id="VAR_086078" FT VARIANT 1255..2554 FT /note="Missing (in MRXS99F; dbSNP:rs869025591)" FT /evidence="ECO:0000269|PubMed:26833328" FT /id="VAR_086079" FT VARIANT 1268..2554 FT /note="Missing (in MRXS99F)" FT /evidence="ECO:0000269|PubMed:26833328" FT /id="VAR_086080" FT VARIANT 1693 FT /note="L -> W (in MRXS99F)" FT /evidence="ECO:0000269|PubMed:26833328" FT /id="VAR_086081" FT VARIANT 2093 FT /note="L -> H (in XLID99; uncertain significance; does not FT affect interaction with DCX; reduced subcellular FT localization in the axonal growth cones; FT dbSNP:rs587777317)" FT /evidence="ECO:0000269|PubMed:24607389" FT /id="VAR_071131" FT VARIANT 2157 FT /note="L -> I (in XLID99; uncertain significance; does not FT affect interaction with DCX; reduced subcellular FT localization in the axonal growth cones; FT dbSNP:rs587777319)" FT /evidence="ECO:0000269|PubMed:24607389" FT /id="VAR_071132" FT VARIANT 2483..2487 FT /note="Missing (in MRXS99F)" FT /evidence="ECO:0000269|PubMed:26833328" FT /id="VAR_086082" FT MUTAGEN 1566 FT /note="C->A: Does not restore RICTOR expression levels when FT introduced into cells where endogenous USP9X has been FT silenced." FT /evidence="ECO:0000269|PubMed:33378666" FT MUTAGEN 1566 FT /note="C->S: Abolished deubiquitinase activity." FT /evidence="ECO:0000269|PubMed:30914461" FT MUTAGEN 1727 FT /note="C->A: Strongly decreased deubiquitinase activity." FT /evidence="ECO:0000269|PubMed:30914461" FT MUTAGEN 1729 FT /note="H->A: Strongly decreased deubiquitinase activity." FT /evidence="ECO:0000269|PubMed:30914461" FT CONFLICT 25 FT /note="Q -> L (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 148..154 FT /note="Missing (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 468 FT /note="L -> P (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 476 FT /note="W -> R (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 506 FT /note="K -> R (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 621 FT /note="A -> V (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 1400 FT /note="L -> F (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 1951 FT /note="L -> P (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT CONFLICT 2330 FT /note="T -> P (in Ref. 1; CAA66942)" FT /evidence="ECO:0000305" FT HELIX 326..344 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 348..364 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 383..393 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 395..402 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 403..405 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 407..422 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 428..436 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 443..456 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 457..459 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 462..478 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 481..496 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 503..515 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 522..538 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 539..541 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 542..544 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 545..547 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 548..559 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 566..579 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 599..608 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 612..631 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 651..664 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 666..668 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 674..681 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 682..686 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 691..704 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 705..707 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 713..719 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 720..724 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 734..751 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 753..755 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 758..760 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 762..764 FT /evidence="ECO:0007829|PDB:7YXX" FT HELIX 771..779 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 783..797 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 802..806 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 808..830 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 843..865 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 889..891 FT /evidence="ECO:0007829|PDB:5VBD" FT HELIX 912..928 FT /evidence="ECO:0007829|PDB:5VBD" FT STRAND 930..936 FT /evidence="ECO:0007829|PDB:5VBD" FT HELIX 943..945 FT /evidence="ECO:0007829|PDB:5VBD" FT HELIX 950..952 FT /evidence="ECO:0007829|PDB:5VBD" FT STRAND 960..967 FT /evidence="ECO:0007829|PDB:5VBD" FT HELIX 1015..1030 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1034..1045 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1048..1050 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1051..1065 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1077..1080 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1085..1099 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1113..1120 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1122..1131 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1133..1135 FT /evidence="ECO:0007829|PDB:7YXX" FT STRAND 1136..1138 FT /evidence="ECO:0007829|PDB:7YXX" FT HELIX 1143..1163 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1236..1250 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1254..1256 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1262..1268 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1276..1278 FT /evidence="ECO:0007829|PDB:7YXX" FT HELIX 1281..1298 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1301..1306 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 1307..1310 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 1311..1313 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1314..1317 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1318..1322 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1326..1338 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1339..1343 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1348..1358 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 1361..1364 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1365..1368 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 1372..1374 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1375..1388 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1397..1416 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1424..1437 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 1445..1447 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 1448..1451 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 1453..1455 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1458..1461 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1462..1467 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1469..1478 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1495..1509 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1513..1527 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 1528..1531 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 1532..1534 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 1542..1544 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 1553..1555 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 1566..1576 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1579..1586 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1634..1656 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1659..1662 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1665..1670 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1686..1703 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1709..1714 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1716..1728 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1730..1742 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1744..1746 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1750..1759 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1761..1763 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1765..1767 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1769..1771 FT /evidence="ECO:0007829|PDB:5WCH" FT TURN 1772..1775 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1776..1778 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1780..1788 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1791..1797 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1800..1803 FT /evidence="ECO:0007829|PDB:5WCH" FT TURN 1804..1807 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1808..1811 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1820..1823 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1825..1827 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1829..1836 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1862..1873 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1875..1877 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1879..1885 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1897..1901 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1904..1907 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1913..1920 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1924..1931 FT /evidence="ECO:0007829|PDB:5WCH" FT TURN 1932..1935 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1936..1943 FT /evidence="ECO:0007829|PDB:5WCH" FT STRAND 1946..1955 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1963..1965 FT /evidence="ECO:0007829|PDB:5WCH" FT HELIX 1989..2004 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2007..2018 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2021..2023 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2035..2051 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2052..2056 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2061..2064 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2068..2078 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2082..2088 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2089..2093 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 2094..2097 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2099..2104 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2110..2126 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 2128..2130 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2133..2135 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2152..2166 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2168..2170 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2176..2187 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2190..2198 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2201..2207 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 2213..2215 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2216..2218 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2226..2237 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2242..2244 FT /evidence="ECO:0007829|PDB:7YXX" FT HELIX 2252..2257 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 2268..2270 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2273..2276 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2277..2281 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2284..2291 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2297..2307 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2311..2326 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2330..2332 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2334..2344 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2351..2359 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 2363..2366 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2369..2376 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2381..2397 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2400..2403 FT /evidence="ECO:0007829|PDB:7YXY" FT TURN 2404..2407 FT /evidence="ECO:0007829|PDB:7YXY" FT HELIX 2409..2427 FT /evidence="ECO:0007829|PDB:7YXY" FT STRAND 2454..2456 FT /evidence="ECO:0007829|PDB:7YXX" FT HELIX 2463..2470 FT /evidence="ECO:0007829|PDB:7YXY" SQ SEQUENCE 2554 AA; 290463 MW; 16B87B7FCC1428AF CRC64; MTATTRGSPV GGNDNQGQAP DGQSQPPLQQ NQTSSPDSSN ENSPATPPDE QGQGDAPPQL EDEEPAFPHT DLAKLDDMIN RPRWVVPVLP KGELEVLLEA AIDLSKKGLD VKSEACQRFF RDGLTISFTK ILTDEAVSGW KFEIHRCIIN NTHRLVELCV AKLSQDWFPL LELLAMALNP HCKFHIYNGT RPCESVSSSV QLPEDELFAR SPDPRSPKGW LVDLLNKFGT LNGFQILHDR FINGSALNVQ IIAALIKPFG QCYEFLTLHT VKKYFLPIIE MVPQFLENLT DEELKKEAKN EAKNDALSMI IKSLKNLASR VPGQEETVKN LEIFRLKMIL RLLQISSFNG KMNALNEVNK VISSVSYYTH RHGNPEEEEW LTAERMAEWI QQNNILSIVL RDSLHQPQYV EKLEKILRFV IKEKALTLQD LDNIWAAQAG KHEAIVKNVH DLLAKLAWDF SPEQLDHLFD CFKASWTNAS KKQREKLLEL IRRLAEDDKD GVMAHKVLNL LWNLAHSDDV PVDIMDLALS AHIKILDYSC SQDRDTQKIQ WIDRFIEELR TNDKWVIPAL KQIREICSLF GEAPQNLSQT QRSPHVFYRH DLINQLQHNH ALVTLVAENL ATYMESMRLY ARDHEDYDPQ TVRLGSRYSH VQEVQERLNF LRFLLKDGQL WLCAPQAKQI WKCLAENAVY LCDREACFKW YSKLMGDEPD LDPDINKDFF ESNVLQLDPS LLTENGMKCF ERFFKAVNCR EGKLVAKRRA YMMDDLELIG LDYLWRVVIQ SNDDIASRAI DLLKEIYTNL GPRLQVNQVV IHEDFIQSCF DRLKASYDTL CVLDGDKDSV NCARQEAVRM VRVLTVLREY INECDSDYHE ERTILPMSRA FRGKHLSFVV RFPNQGRQVD DLEVWSHTND TIGSVRRCIL NRIKANVAHT KIELFVGGEL IDPADDRKLI GQLNLKDKSL ITAKLTQISS NMPSSPDSSS DSSTGSPGNH GNHYSDGPNP EVESCLPGVI MSLHPRYISF LWQVADLGSS LNMPPLRDGA RVLMKLMPPD STTIEKLRAI CLDHAKLGES SLSPSLDSLF FGPSASQVLY LTEVVYALLM PAGAPLADDS SDFQFHFLKS GGLPLVLSML TRNNFLPNAD METRRGAYLN ALKIAKLLLT AIGYGHVRAV AEACQPGVEG VNPMTQINQV THDQAVVLQS ALQSIPNPSS ECMLRNVSVR LAQQISDEAS RYMPDICVIR AIQKIIWASG CGSLQLVFSP NEEITKIYEK TNAGNEPDLE DEQVCCEALE VMTLCFALIP TALDALSKEK AWQTFIIDLL LHCHSKTVRQ VAQEQFFLMC TRCCMGHRPL LFFITLLFTV LGSTARERAK HSGDYFTLLR HLLNYAYNSN INVPNAEVLL NNEIDWLKRI RDDVKRTGET GIEETILEGH LGVTKELLAF QTSEKKFHIG CEKGGANLIK ELIDDFIFPA SNVYLQYMRN GELPAEQAIP VCGSPPTINA GFELLVALAV GCVRNLKQIV DSLTEMYYIG TAITTCEALT EWEYLPPVGP RPPKGFVGLK NAGATCYMNS VIQQLYMIPS IRNGILAIEG TGSDVDDDMS GDEKQDNESN VDPRDDVFGY PQQFEDKPAL SKTEDRKEYN IGVLRHLQVI FGHLAASRLQ YYVPRGFWKQ FRLWGEPVNL REQHDALEFF NSLVDSLDEA LKALGHPAML SKVLGGSFAD QKICQGCPHR YECEESFTTL NVDIRNHQNL LDSLEQYVKG DLLEGANAYH CEKCNKKVDT VKRLLIKKLP PVLAIQLKRF DYDWERECAI KFNDYFEFPR ELDMEPYTVA GVAKLEGDNV NPESQLIQQS EQSESETAGS TKYRLVGVLV HSGQASGGHY YSYIIQRNGG DGERNRWYKF DDGDVTECKM DDDEEMKNQC FGGEYMGEVF DHMMKRMSYR RQKRWWNAYI LFYERMDTID QDDELIRYIS ELAITTRPHQ IIMPSAIERS VRKQNVQFMH NRMQYSMEYF QFMKKLLTCN GVYLNPPPGQ DHLLPEAEEI TMISIQLAAR FLFTTGFHTK KVVRGSASDW YDALCILLRH SKNVRFWFAH NVLFNVSNRF SEYLLECPSA EVRGAFAKLI VFIAHFSLQD GPCPSPFASP GPSSQAYDNL SLSDHLLRAV LNLLRREVSE HGRHLQQYFN LFVMYANLGV AEKTQLLKLS VPATFMLVSL DEGPGPPIKY QYAELGKLYS VVSQLIRCCN VSSRMQSSIN GNPPLPNPFG DPNLSQPIMP IQQNVADILF VRTSYVKKII EDCSNSEETV KLLRFCCWEN PQFSSTVLSE LLWQVAYSYT YELRPYLDLL LQILLIEDSW QTHRIHNALK GIPDDRDGLF DTIQRSKNHY QKRAYQCIKC MVALFSNCPV AYQILQGNGD LKRKWTWAVE WLGDELERRP YTGNPQYTYN NWSPPVQSNE TSNGYFLERS HSARMTLAKA CELCPEEEPD DQDAPDEHES PPPEDAPLYP HSPGSQYQQN NHVHGQPYTG PAAHHMNNPQ RTGQRAQENY EGSEEVSPPQ TKDQ //