8bs9

Structure of USP36 in complex with Ubiquitin-PAStructure of USP36 in complex with Ubiquitin-PA

Structural highlights

8bs9 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP36_HUMAN Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:29273634, PubMed:19208757, PubMed:22902402). Required for cell and organism viability (PubMed:29273634, PubMed:19208757, PubMed:22902402). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:29273634, PubMed:19208757, PubMed:22902402). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

References

↑ Endo A, Matsumoto M, Inada T, Yamamoto A, Nakayama KI, Kitamura N, Komada M. Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36. J Cell Sci. 2009 Mar 1;122(Pt 5):678-86. PMID:19208757 doi:10.1242/jcs.044461
↑ Kim MS, Ramakrishna S, Lim KH, Kim JH, Baek KH. Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36. J Cell Biochem. 2011 Feb;112(2):498-508. PMID:21268071 doi:10.1002/jcb.22940
↑ Taillebourg E, Gregoire I, Viargues P, Jacomin AC, Thevenon D, Faure M, Fauvarque MO. The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins. Autophagy. 2012 May 1;8(5):767-79. PMID:22622177 doi:10.4161/auto.19381
↑ Richardson LA, Reed BJ, Charette JM, Freed EF, Fredrickson EK, Locke MN, Baserga SJ, Gardner RG. A conserved deubiquitinating enzyme controls cell growth by regulating RNA polymerase I stability. Cell Rep. 2012 Aug 30;2(2):372-85. doi: 10.1016/j.celrep.2012.07.009. Epub 2012, Aug 16. PMID:22902402 doi:http://dx.doi.org/10.1016/j.celrep.2012.07.009
↑ Sun XX, He X, Yin L, Komada M, Sears RC, Dai MS. The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3734-9. PMID:25775507 doi:10.1073/pnas.1411713112
↑ Anta B, Martín-Rodríguez C, Gomis-Perez C, Calvo L, López-Benito S, Calderón-García AA, Vicente-García C, Villarroel Á, Arévalo JC. Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3). J Biol Chem. 2016 Sep 2;291(36):19132-45. PMID:27445338 doi:10.1074/jbc.M116.722637
↑ Fraile JM, Campos-Iglesias D, Rodríguez F, Astudillo A, Vilarrasa-Blasi R, Verdaguer-Dot N, Prado MA, Paulo JA, Gygi SP, Martín-Subero JI, Freije JMP, López-Otín C. Loss of the deubiquitinase USP36 destabilizes the RNA helicase DHX33 and causes preimplantation lethality in mice. J Biol Chem. 2018 Feb 9;293(6):2183-2194. PMID:29273634 doi:10.1074/jbc.M117.788430
↑ DeVine T, Sears RC, Dai MS. The ubiquitin-specific protease USP36 is a conserved histone H2B deubiquitinase. Biochem Biophys Res Commun. 2018 Jan 15;495(3):2363-2368. PMID:29274341 doi:10.1016/j.bbrc.2017.12.107
↑ Ling H, Cao CH, Han K, Lv YR, Ma XD, Cao JH, Chen JW, Li S, Lin JL, Fang YJ, Pan ZZ, Xie D, Wang FW. CEP63 upregulates YAP1 to promote colorectal cancer progression through stabilizing RNA binding protein FXR1. Oncogene. 2022 Sep;41(39):4433-4445. PMID:35989368 doi:10.1038/s41388-022-02439-y

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OCA

[1] Endo A, Matsumoto M, Inada T, Yamamoto A, Nakayama KI, Kitamura N, Komada M. Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36. J Cell Sci. 2009 Mar 1;122(Pt 5):678-86. PMID:19208757 doi:10.1242/jcs.044461

[2] Kim MS, Ramakrishna S, Lim KH, Kim JH, Baek KH. Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36. J Cell Biochem. 2011 Feb;112(2):498-508. PMID:21268071 doi:10.1002/jcb.22940

[3] Taillebourg E, Gregoire I, Viargues P, Jacomin AC, Thevenon D, Faure M, Fauvarque MO. The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins. Autophagy. 2012 May 1;8(5):767-79. PMID:22622177 doi:10.4161/auto.19381

[4] Richardson LA, Reed BJ, Charette JM, Freed EF, Fredrickson EK, Locke MN, Baserga SJ, Gardner RG. A conserved deubiquitinating enzyme controls cell growth by regulating RNA polymerase I stability. Cell Rep. 2012 Aug 30;2(2):372-85. doi: 10.1016/j.celrep.2012.07.009. Epub 2012, Aug 16. PMID:22902402 doi:http://dx.doi.org/10.1016/j.celrep.2012.07.009

[5] Sun XX, He X, Yin L, Komada M, Sears RC, Dai MS. The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3734-9. PMID:25775507 doi:10.1073/pnas.1411713112

[6] Anta B, Martín-Rodríguez C, Gomis-Perez C, Calvo L, López-Benito S, Calderón-García AA, Vicente-García C, Villarroel Á, Arévalo JC. Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3). J Biol Chem. 2016 Sep 2;291(36):19132-45. PMID:27445338 doi:10.1074/jbc.M116.722637

[7] Fraile JM, Campos-Iglesias D, Rodríguez F, Astudillo A, Vilarrasa-Blasi R, Verdaguer-Dot N, Prado MA, Paulo JA, Gygi SP, Martín-Subero JI, Freije JMP, López-Otín C. Loss of the deubiquitinase USP36 destabilizes the RNA helicase DHX33 and causes preimplantation lethality in mice. J Biol Chem. 2018 Feb 9;293(6):2183-2194. PMID:29273634 doi:10.1074/jbc.M117.788430

[8] DeVine T, Sears RC, Dai MS. The ubiquitin-specific protease USP36 is a conserved histone H2B deubiquitinase. Biochem Biophys Res Commun. 2018 Jan 15;495(3):2363-2368. PMID:29274341 doi:10.1016/j.bbrc.2017.12.107

[9] Ling H, Cao CH, Han K, Lv YR, Ma XD, Cao JH, Chen JW, Li S, Lin JL, Fang YJ, Pan ZZ, Xie D, Wang FW. CEP63 upregulates YAP1 to promote colorectal cancer progression through stabilizing RNA binding protein FXR1. Oncogene. 2022 Sep;41(39):4433-4445. PMID:35989368 doi:10.1038/s41388-022-02439-y

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