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It was originally identified as the major deubiquitinase for histone H2A and has since been found to deubiquitinate a range of other substrates, including proteins from both the cytoplasm and nucleus. USP16 is phosphorylated when cells enter mitosis and dephosphorylated during the metaphase\/anaphase transition. While much of USP16 is localized in the cytoplasm, separating the enzyme from its substrates is considered an important regulatory mechanism. Some of the functions that USP16 has been linked to include DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility. 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Cell Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1186\/s12935-021-02160-y","article-title":"The Role of the Deubiquitinating Enzyme Dub3\/Usp17 in Cancer: A Narrative Review","volume":"21","author":"Yang","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.chembiol.2011.10.017","article-title":"The Differential Modulation of Usp Activity by Internal Regulatory Domains, Interactors and Eight Ubiquitin Chain Types","volume":"18","author":"Faesen","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1038\/ncomms5763","article-title":"Screening of Dub Activity and Specificity by Maldi-Tof Mass Spectrometry","volume":"5","author":"Ritorto","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Takahashi, H., Yamanaka, S., Kuwada, S., Higaki, K., Kido, K., Sato, Y., Fukai, S., Tokunaga, F., and Sawasaki, T. (2020). A Human Dub Protein Array for Clarification of Linkage Specificity of Polyubiquitin Chain and Application to Evaluation of Its Inhibitors. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060152"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1073\/pnas.1815027116","article-title":"Crystal Structure and Activity-Based Labeling Reveal the Mechanisms for Linkage-Specific Substrate Recognition by Deubiquitinase Usp9x","volume":"116","author":"Paudel","year":"2019","journal-title":"Proc. Natl. Acad. Sci. 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USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/nature06256","article-title":"Regulation of Cell Cycle Progression and Gene Expression by H2a Deubiquitination","volume":"449","author":"Joo","year":"2007","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.cell.2012.08.005","article-title":"Rnf168 Ubiquitinates K13-15 on H2a\/H2ax to Drive DNA Damage Signaling","volume":"150","author":"Mattiroli","year":"2012","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32883","DOI":"10.1074\/jbc.M114.599605","article-title":"The Histone H2a Deubiquitinase Usp16 Interacts with Herc2 and Fine-Tunes Cellular Response to DNA Damage","volume":"289","author":"Zhang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.4161\/cc.26278","article-title":"Ubp-M Serine 552 Phosphorylation by Cyclin-Dependent Kinase 1 Regulates Cell Cycle Progression","volume":"12","author":"Xu","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature12530","article-title":"Usp16 Contributes to Somatic Stem-Cell Defects in Down\u2019s Syndrome","volume":"501","author":"Adorno","year":"2013","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1038\/ncomms4818","article-title":"The Histone H2a Deubiquitinase Usp16 Regulates Embryonic Stem Cell Gene Expression and Lineage Commitment","volume":"5","author":"Yang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E51","DOI":"10.1073\/pnas.1517041113","article-title":"The Histone H2a Deubiquitinase Usp16 Regulates Hematopoiesis and Hematopoietic Stem Cell Function","volume":"113","author":"Gu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"jcs239236","DOI":"10.1242\/jcs.239236","article-title":"A Potent Nuclear Export Mechanism Imposes Usp16 Cytoplasmic Localization during Interphase","volume":"133","author":"Daou","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"326","DOI":"10.15252\/embj.201489184","article-title":"Usp45 Deubiquitylase Controls Ercc1-Xpf Endonuclease-Mediated DNA Damage Responses","volume":"34","author":"Lachaud","year":"2015","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/mp\/sst150","article-title":"Prc1 Marks the Difference in Plant Pcg Repression","volume":"7","author":"Calonje","year":"2014","journal-title":"Mol. Plant"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/tpj.12818","article-title":"Prc1 Is Taking the Lead in Pcg Repression","volume":"83","author":"Merini","year":"2015","journal-title":"Plant J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/gbe\/evx020","article-title":"The Evolution and Functional Diversification of the Deubiquitinating Enzyme Superfamily","volume":"9","author":"Vlasschaert","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jmb.2007.04.015","article-title":"Solution Structure of the Ubp-M Buz Domain, a Highly Specific Protein Module That Recognizes the C-Terminal Tail of Free Ubiquitin","volume":"370","author":"Pai","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with Alphafold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Evans, R., O\u2019Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., \u017d\u00eddek, A., Bates, R., Blackwell, S., and Yim, J. (2022). Protein Complex Prediction with Alphafold-Multimer. bioRxiv.","DOI":"10.1101\/2021.10.04.463034"},{"key":"ref_29","unstructured":"Schrodinger, L.L.C. (2015). The Pymol Molecular Graphics System, Version 1.8, PyMOL."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/nsmb.3475","article-title":"Mechanism and Regulation of the Lys6-Selective Deubiquitinase Usp30","volume":"24","author":"Gersch","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e54435","DOI":"10.7554\/eLife.54435","article-title":"Usp16 Counteracts Mono-Ubiquitination of Rps27a and Promotes Maturation of the 40s Ribosomal Subunit","volume":"9","author":"Montellese","year":"2020","journal-title":"Elife"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down Syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature12558","article-title":"Stem Cells: Down\u2019s Syndrome Link to Ageing","volume":"501","author":"Souroullas","year":"2013","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1038\/emboj.2013.220","article-title":"Usp16: Key Controller of Stem Cells in Down Syndrome","volume":"32","author":"Xu","year":"2013","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13041-019-0535-3","article-title":"Transcriptional Activation of Usp16 Gene Expression by Nf\u03bab Signaling","volume":"12","author":"Yang","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"eabc4009","DOI":"10.1126\/sciadv.abc4009","article-title":"Substrate-Specific Recognition of Ikks Mediated by Usp16 Facilitates Autoimmune Inflammation","volume":"7","author":"Yu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ajh.26455","article-title":"Chronic Myelomonocytic Leukemia: 2022 Update on Diagnosis, Risk Stratification, and Management","volume":"97","author":"Patnaik","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gelsi-Boyer, V., Trouplin, V., Ad\u00e9la\u00efde, J., Aceto, N., Remy, V., Pinson, S., Houdayer, C., Arnoulet, C., Sainty, D., and Bentires-Alj, M. (2008). Genome Profiling of Chronic Myelomonocytic Leukemia: Frequent Alterations of Ras and Runx1 Genes. BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-299"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10238","DOI":"10.3748\/wjg.v20.i30.10238","article-title":"Hepatitis B Virus, Hbx Mutants and Their Role in Hepatocellular Carcinoma","volume":"20","author":"Ali","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33039","DOI":"10.1038\/srep33039","article-title":"Usp16 Downregulation by Carboxyl-Terminal Truncated Hbx Promotes the Growth of Hepatocellular Carcinoma Cells","volume":"6","author":"Qian","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5599","DOI":"10.1093\/nar\/gkac468","article-title":"Usp16-Mediated Histone H2a Lysine-119 Deubiquitination during Oocyte Maturation Is a Prerequisite for Zygotic Genome Activation","volume":"50","author":"Rong","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17506","DOI":"10.1038\/s41598-018-34562-w","article-title":"Usp16 Modulates Wnt Signaling in Primary Tissues through Cdkn2a Regulation","volume":"8","author":"Adorno","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e66037","DOI":"10.7554\/eLife.66037","article-title":"Inhibiting Usp16 Rescues Stem Cell Aging and Memory in an Alzheimer\u2019s Model","volume":"11","author":"Reinitz","year":"2022","journal-title":"Elife"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eabn2571","DOI":"10.1126\/sciadv.abn2571","article-title":"Critical Role of Lncepat in Coupling Dysregulated Egfr Pathway and Histone H2a Deubiquitination during Glioblastoma Tumorigenesis","volume":"8","author":"Li","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1083\/jcb.201502044","article-title":"Usp16 Regulates Kinetochore Localization of Plk1 to Promote Proper Chromosome Alignment in Mitosis","volume":"210","author":"Zhuo","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13046-021-01843-8","article-title":"Usp16 Regulates Castration-Resistant Prostate Cancer Cell Proliferation by Deubiquitinating and Stablizing C-Myc","volume":"40","author":"Ge","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1172\/JCI123801","article-title":"Usp16-Mediated Deubiquitination of Calcineurin a Controls Peripheral T Cell Maintenance","volume":"129","author":"Zhang","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"215862","DOI":"10.1016\/j.canlet.2022.215862","article-title":"Lncrna Mnx1-As1 Sustains Inactivation of Hippo Pathway through a Positive Feedback Loop with Usp16\/Igf2bp3 Axis in Gallbladder Cancer","volume":"547","author":"Liu","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.1038\/s41388-021-01964-6","article-title":"The Deubiquitinase Usp16 Functions as an Oncogenic Factor in K-Ras-Driven Lung Tumorigenesis","volume":"40","author":"Xu","year":"2021","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1536\/ihj.20-043","article-title":"Usp16 Regulates the Stability and Function of Ldl Receptor by Deubiquitination","volume":"61","author":"Li","year":"2020","journal-title":"Int. Heart J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eabn0968","DOI":"10.1126\/sciadv.abn0968","article-title":"Loss-of-Function Mutations in Cep78 Cause Male Infertility in Humans and Mice","volume":"8","author":"Zhang","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.molcel.2013.08.022","article-title":"The Aurora B Kinase and the Polycomb Protein Ring1b Combine to Regulate Active Promoters in Quiescent Lymphocytes","volume":"51","author":"Frangini","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gopinathan, G., and Diekwisch, T.G.H. (2022). Epigenetics and Early Development. J. Dev. Biol., 10.","DOI":"10.3390\/jdb10020026"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.dnarep.2017.06.011","article-title":"Histone Ubiquitination in the DNA Damage Response","volume":"56","author":"Uckelmann","year":"2017","journal-title":"DNA Repair"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cell.2009.04.042","article-title":"Defining the Human Deubiquitinating Enzyme Interaction Landscape","volume":"138","author":"Sowa","year":"2009","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.cell.2010.04.038","article-title":"Atm-Dependent Chromatin Changes Silence Transcription in Cis to DNA Double-Strand Breaks","volume":"141","author":"Shanbhag","year":"2010","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1038\/onc.2017.113","article-title":"Playing Polo during Mitosis: Plk1 Takes the Lead","volume":"36","author":"Combes","year":"2017","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1007\/s00018-017-2457-5","article-title":"The Equilibrium of Ubiquitination and Deubiquitination at Plk1 Regulates Sister Chromatid Separation","volume":"74","author":"Liu","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12943-020-01291-6","article-title":"Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit C-Myc","volume":"20","author":"Madden","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3389\/fimmu.2020.00195","article-title":"The Role of Calcium-Calcineurin-Nfat Signaling Pathway in Health and Autoimmune Diseases","volume":"11","author":"Park","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Li, T., Zhou, S., Yang, Y., Xu, Y., Gong, X., Cheng, Y., and Wang, Y. (2022). Lncrna Mnx1-As1: A Novel Oncogenic Propellant in Cancers. Biomed. Pharmacother., 149.","DOI":"10.1016\/j.biopha.2022.112801"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/S0140-6736(20)32233-9","article-title":"Elevated Ldl Cholesterol and Increased Risk of Myocardial Infarction and Atherosclerotic Cardiovascular Disease in Individuals Aged 70\u2013100 Years: A Contemporary Primary Prevention Cohort","volume":"396","author":"Mortensen","year":"2020","journal-title":"Lancet"},{"key":"ref_63","first-page":"19","article-title":"Low-Density Lipoprotein Receptor (Ldlr) Family Orchestrates Cholesterol Homeostasis","volume":"85","author":"Go","year":"2012","journal-title":"Yale J. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev-biochem-013118-110817","article-title":"Eukaryotic Ribosome Assembly","volume":"88","author":"Hurt","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/gb-2008-9-7-229","article-title":"The Tektin Family of Microtubule-Stabilizing Proteins","volume":"9","author":"Amos","year":"2008","journal-title":"Genome Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41467-018-08255-x","article-title":"Bap1 Complex Promotes Transcription by Opposing Prc1-Mediated H2a Ubiquitylation","volume":"10","author":"Campagne","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10292","DOI":"10.1038\/ncomms10292","article-title":"Bap1\/Asxl1 Recruitment and Activation for H2a Deubiquitination","volume":"7","author":"Sahtoe","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"679544","DOI":"10.3389\/fcell.2021.679544","article-title":"Crispr-Cas9 Editing of Human Histone Deubiquitinase Gene Usp16 in Human Monocytic Leukemia Cell Line Thp-1","volume":"9","author":"Lefevre","year":"2021","journal-title":"Front. Cell Dev. 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