9yc2

Structural highlights

Function

UBP49_HUMAN Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity. Specifically deubiquitinates histone H2B at 'Lys-120' (H2BK120Ub), a specific tag for epigenetic transcriptional activation and acts as a regulator of mRNA splicing (PubMed:23824326). Antagonizes DNA double-strand break-induced ubiquitination of H2AX thereby participating in the maintenance of genome integrity (PubMed:35598681). Plays a role in the negative regulation of cell proliferation through the AKT pathway by deubiquitinating FKBP51, leading to enhanced AKT1 dephosphorylation by PHLPP1 (PubMed:28363942). Also regulates the mitotic spindle checkpoint and prevents aneuploidy (PubMed:36702832). Negatively regulates cellular antiviral responses via deconjugating 'Lys-63'-linked ubiquitination of STING1 (PubMed:30943264). Significantly enhances the anti-HIV-1 activity of APOBEC3G. Mechanistically, stabilizes APOBEC3G by counteracting HIV-1 Vif-mediated APOBEC3G ubiquitination (PubMed:31397674).^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Zhang Z, Jones A, Joo HY, Zhou D, Cao Y, Chen S, Erdjument-Bromage H, Renfrow M, He H, Tempst P, Townes TM, Giles KE, Ma L, Wang H. USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing. Genes Dev. 2013 Jul 15;27(14):1581-95. PMID:23824326 doi:10.1101/gad.211037.112
2. ↑ Luo K, Li Y, Yin Y, Li L, Wu C, Chen Y, Nowsheen S, Hu Q, Zhang L, Lou Z, Yuan J. USP49 negatively regulates tumorigenesis and chemoresistance through FKBP51-AKT signaling. EMBO J. 2017 May 15;36(10):1434-1446. PMID:28363942 doi:10.15252/embj.201695669
3. ↑ Ye L, Zhang Q, Liuyu T, Xu Z, Zhang MX, Luo MH, Zeng WB, Zhu Q, Lin D, Zhong B. USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA. PLoS Pathog. 2019 Apr 3;15(4):e1007680. PMID:30943264 doi:10.1371/journal.ppat.1007680
4. ↑ Pan T, Song Z, Wu L, Liu G, Ma X, Peng Z, Zhou M, Liang L, Liu B, Liu J, Zhang J, Zhang X, Huang R, Zhao J, Li Y, Ling X, Luo Y, Tang X, Cai W, Deng K, Li L, Zhang H. USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication. Elife. 2019 Aug 9;8:e48318. PMID:31397674 doi:10.7554/eLife.48318
5. ↑ Matsui M, Kajita S, Tsuchiya Y, Torii W, Tamekuni S, Nishi R. USP49 is a novel deubiquitylating enzyme for γ H2AX in DNA double-strand break repair. Gene. 2022 Jul 30;833:146599. PMID:35598681 doi:10.1016/j.gene.2022.146599
6. ↑ Campos-Iglesias D, Fraile JM, Bretones G, Montero AA, Bonzon-Kulichenko E, Vázquez J, López-Otín C, Freije JMP. USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy. Cell Death Dis. 2023 Jan 26;14(1):60. PMID:36702832 doi:10.1038/s41419-023-05600-x