3u12

The pleckstrin homology (PH) domain of USP37The pleckstrin homology (PH) domain of USP37

Structural highlights

3u12 is a 2 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 2.08Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP37_HUMAN Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response (PubMed:26299517, PubMed:27296872, PubMed:31911859, PubMed:34509474). Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872). Plays also an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability (PubMed:34509474). Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM (PubMed:34606619). Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM (PubMed:34606619). Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI (PubMed:31911859). Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination (PubMed:26299517).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Huang X, Summers MK, Pham V, Lill JR, Liu J, Lee G, Kirkpatrick DS, Jackson PK, Fang G, Dixit VM. Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry. Mol Cell. 2011 May 20;42(4):511-23. doi: 10.1016/j.molcel.2011.03.027. PMID:21596315 doi:10.1016/j.molcel.2011.03.027
↑ Yeh C, Coyaud É, Bashkurov M, van der Lelij P, Cheung SW, Peters JM, Raught B, Pelletier L. The Deubiquitinase USP37 Regulates Chromosome Cohesion and Mitotic Progression. Curr Biol. 2015 Aug 31;25(17):2290-9. PMID:26299517 doi:10.1016/j.cub.2015.07.025
↑ Hernández-Pérez S, Cabrera E, Amoedo H, Rodríguez-Acebes S, Koundrioukoff S, Debatisse M, Méndez J, Freire R. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication. Mol Oncol. 2016 Oct;10(8):1196-206. PMID:27296872 doi:10.1016/j.molonc.2016.05.008
↑ Xiao Z, Chang L, Kim J, Zhang P, Hang Q, Yap S, Guo Y, Zhou Z, Zeng L, Hu X, Siverly A, Sun Y, Ma L. USP37 is a SNAI1 deubiquitinase. Am J Cancer Res. 2019 Dec 1;9(12):2749-2759. eCollection 2019 PMID:31911859
↑ Stromberg BR, Singh M, Torres AE, Burrows AC, Pal D, Insinna C, Rhee Y, Dickson AS, Westlake CJ, Summers MK. The deubiquitinating enzyme USP37 enhances CHK1 activity to promote the cellular response to replication stress. J Biol Chem. 2021 Oct;297(4):101184. PMID:34509474 doi:10.1016/j.jbc.2021.101184
↑ Wu C, Chang Y, Chen J, Su Y, Li L, Chen Y, Li Y, Wu J, Huang J, Zhao F, Wang W, Yin H, Wang S, Jin M, Lou Z, Zhu WG, Luo K, Zhang J, Yuan J. USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM. Nucleic Acids Res. 2021 Nov 8;49(19):11224-11240. PMID:34606619 doi:10.1093/nar/gkab842

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OCA

[1] Huang X, Summers MK, Pham V, Lill JR, Liu J, Lee G, Kirkpatrick DS, Jackson PK, Fang G, Dixit VM. Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry. Mol Cell. 2011 May 20;42(4):511-23. doi: 10.1016/j.molcel.2011.03.027. PMID:21596315 doi:10.1016/j.molcel.2011.03.027

[2] Yeh C, Coyaud É, Bashkurov M, van der Lelij P, Cheung SW, Peters JM, Raught B, Pelletier L. The Deubiquitinase USP37 Regulates Chromosome Cohesion and Mitotic Progression. Curr Biol. 2015 Aug 31;25(17):2290-9. PMID:26299517 doi:10.1016/j.cub.2015.07.025

[3] Hernández-Pérez S, Cabrera E, Amoedo H, Rodríguez-Acebes S, Koundrioukoff S, Debatisse M, Méndez J, Freire R. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication. Mol Oncol. 2016 Oct;10(8):1196-206. PMID:27296872 doi:10.1016/j.molonc.2016.05.008

[4] Xiao Z, Chang L, Kim J, Zhang P, Hang Q, Yap S, Guo Y, Zhou Z, Zeng L, Hu X, Siverly A, Sun Y, Ma L. USP37 is a SNAI1 deubiquitinase. Am J Cancer Res. 2019 Dec 1;9(12):2749-2759. eCollection 2019 PMID:31911859

[5] Stromberg BR, Singh M, Torres AE, Burrows AC, Pal D, Insinna C, Rhee Y, Dickson AS, Westlake CJ, Summers MK. The deubiquitinating enzyme USP37 enhances CHK1 activity to promote the cellular response to replication stress. J Biol Chem. 2021 Oct;297(4):101184. PMID:34509474 doi:10.1016/j.jbc.2021.101184

[6] Wu C, Chang Y, Chen J, Su Y, Li L, Chen Y, Li Y, Wu J, Huang J, Zhao F, Wang W, Yin H, Wang S, Jin M, Lou Z, Zhu WG, Luo K, Zhang J, Yuan J. USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM. Nucleic Acids Res. 2021 Nov 8;49(19):11224-11240. PMID:34606619 doi:10.1093/nar/gkab842

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