Genomes and Genes
Gene Symbol: SUMO2
Description: small ubiquitin-like modifier 2
Alias: HSMT3, SMT3B, SMT3H2, SUMO3, Smt3A, small ubiquitin-related modifier 2, SMT3 homolog 2, SMT3 suppressor of mif two 3 homolog 2, sentrin 2, ubiquitin-like protein SMT3A, ubiquitin-like protein SMT3B
- Ayaydin F, Dasso M. Distinct in vivo dynamics of vertebrate SUMO paralogues. Mol Biol Cell. 2004;15:5208-18 pubmed
- Huang W, Ko T, Li S, Wang A. Crystal structures of the human SUMO-2 protein at 1.6 A and 1.2 A resolution: implication on the functional differences of SUMO proteins. Eur J Biochem. 2004;271:4114-22 pubmed..This may explain their distinct intracellular locations. In addition, crystal-packing analysis suggests a possible trimeric assembly of the SUMO-2 protein, of which the biological significance remains to be determined. ..
- Rojas Fernandez A, PlechanovovÃ¡ A, Hattersley N, Jaffray E, Tatham M, Hay R. SUMO chain-induced dimerization activates RNF4. Mol Cell. 2014;53:880-92 pubmed publisher..Thus the ubiquitin E3 ligase activity of RNF4 is directly linked to the availability of its polySUMO substrates. ..
- Shen L, Dong C, Liu H, Naismith J, Hay R. The structure of SENP1-SUMO-2 complex suggests a structural basis for discrimination between SUMO paralogues during processing. Biochem J. 2006;397:279-88 pubmed
- Hardeland U, Steinacher R, Jiricny J, Schär P. Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. EMBO J. 2002;21:1456-64 pubmed..These observations implicate a function of sumoylation in the controlled dissociation of TDG from the AP site and open up novel perspectives for the understanding of the molecular mechanisms coordinating the early steps of BER. ..
- El McHichi B, Regad T, Maroui M, Rodriguez M, Aminev A, Gerbaud S, et al. SUMOylation promotes PML degradation during encephalomyocarditis virus infection. J Virol. 2010;84:11634-45 pubmed publisher..Together, these findings reveal a new mechanism evolved by EMCV to antagonize the PML pathway in the interferon-induced antiviral defense. ..
- Liang Q, Deng H, Li X, Wu X, Tang Q, Chang T, et al. Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7. J Immunol. 2011;187:4754-63 pubmed publisher..Collectively, our results suggest that TRIM28 is a specific SUMO E3 ligase and negative regulator of IRF7. ..
- Reverter D, Lima C. A basis for SUMO protease specificity provided by analysis of human Senp2 and a Senp2-SUMO complex. Structure. 2004;12:1519-31 pubmed
- Boutell C, Cuchet Louren o D, Vanni E, Orr A, Glass M, McFarlane S, et al. A viral ubiquitin ligase has substrate preferential SUMO targeted ubiquitin ligase activity that counteracts intrinsic antiviral defence. PLoS Pathog. 2011;7:e1002245 pubmed publisher..We conclude that ICP0 has dual targeting mechanisms involving both SUMO- and substrate-dependent targeting specificities in order to counteract intrinsic antiviral resistance to HSV-1 infection...
- Lapenta V, Chiurazzi P, Van der Spek P, Pizzuti A, Hanaoka F, Brahe C. SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family. Genomics. 1997;40:362-6 pubmed..A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere...
- Kamitani T, Kito K, Nguyen H, Fukuda Kamitani T, Yeh E. Characterization of a second member of the sentrin family of ubiquitin-like proteins. J Biol Chem. 1998;273:11349-53 pubmed..Immunocytochemical analysis showed that sentrin-2 derivatives were highly enriched in the nucleus. Taken together, our results demonstrate that sentrin-2 is another protein modifier for the sentrinization pathway. ..
- Finkbeiner E, Haindl M, Muller S. The SUMO system controls nucleolar partitioning of a novel mammalian ribosome biogenesis complex. EMBO J. 2011;30:1067-78 pubmed publisher..These findings contribute to the basic understanding of mammalian ribosome biogenesis and shed new light on the role of SUMO in this process. ..
- Sang J, Yang K, Sun Y, Han Y, Cang H, Chen Y, et al. SUMO2 and SUMO3 transcription is differentially regulated by oxidative stress in an Sp1-dependent manner. Biochem J. 2011;435:489-98 pubmed publisher..SUMO isoforms SUMO2 and SUMO3 can rapidly convert to be conjugated in response to a variety of cellular stresses...
- Jacobs A, Nicol S, Hislop R, Jaffray E, Hay R, Fuller Pace F. SUMO modification of the DEAD box protein p68 modulates its transcriptional activity and promotes its interaction with HDAC1. Oncogene. 2007;26:5866-76 pubmed..These findings may be explained by the ability of wild type, but not K53R p68, to alter the modification state of chromatin by recruitment of histone deacetylase 1 (HDAC1). ..
- Gong L, Yeh E. Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3. J Biol Chem. 2006;281:15869-77 pubmed..Thus, SENP3 and SENP5 constitute a subfamily of SENPs that regulate the formation of SUMO-2 or SUMO-3 conjugates and, to a less extent, SUMO-1 modification. ..
- Tatham M, PlechanovovÃ¡ A, Jaffray E, Salmen H, Hay R. Ube2W conjugates ubiquitin to Î±-amino groups of protein N-termini. Biochem J. 2013;453:137-45 pubmed publisher..The description in the present study is the first of an E2-conjugating enzyme with N-terminal ubiquitylation activity, and highlights the importance of E2 enzymes in the ultimate outcome of E3-mediated ubiquitylation. ..
- Galanty Y, Belotserkovskaya R, Coates J, Polo S, Miller K, Jackson S. Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature. 2009;462:935-9 pubmed publisher..Here, we show that SUMO1, SUMO2 and SUMO3 accumulate at DSB sites in mammalian cells, with SUMO1 and SUMO2/3 accrual requiring the E3 ligase enzymes PIAS4 ..
- Morris J, Boutell C, Keppler M, Densham R, Weekes D, Alamshah A, et al. The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature. 2009;462:886-90 pubmed publisher..modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9...
- Keusekotten K, Bade V, Meyer Teschendorf K, Sriramachandran A, Fischer Schrader K, Krause A, et al. Multivalent interactions of the SUMO-interaction motifs in RING finger protein 4 determine the specificity for chains of the SUMO. Biochem J. 2014;457:207-14 pubmed publisher..In the present paper, we describe that the sequence and spacing of the SIMs (SUMO-interaction motifs) in RNF4 regulate the avidity-driven recognition of substrate proteins carrying SUMO chains of variable length. ..
- Hu G, Xu C, Staudinger J. Pregnane X receptor is SUMOylated to repress the inflammatory response. J Pharmacol Exp Ther. 2010;335:342-50 pubmed publisher..We provide evidence that the SUMOylated PXR contains SUMO3 chains, and feedback represses the immune response in hepatocytes...
- Li T, Santockyte R, Shen R, Tekle E, Wang G, Yang D, et al. Expression of SUMO-2/3 induced senescence through p53- and pRB-mediated pathways. J Biol Chem. 2006;281:36221-7 pubmed..Together, our results reveal that p53 and pRB can be sumoylated by SUMO-2/3 in vivo, and such modification of p53 and pRB may play roles in premature senescence and stress response. ..
- Hattersley N, Shen L, Jaffray E, Hay R. The SUMO protease SENP6 is a direct regulator of PML nuclear bodies. Mol Biol Cell. 2011;22:78-90 pubmed publisher..Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6. ..
- Tatham M, Geoffroy M, Shen L, Plechanovova A, Hattersley N, Jaffray E, et al. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008;10:538-46 pubmed publisher..These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis. ..
- Rabellino A, Carter B, Konstantinidou G, Wu S, Rimessi A, Byers L, et al. The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA. Cancer Res. 2012;72:2275-84 pubmed publisher..Together, our findings reveal novel roles for PIAS1 and the SUMOylation machinery in regulating oncogenic networks and the response to leukemia therapy. ..
- Sun H, Hunter T. Poly-small ubiquitin-like modifier (PolySUMO)-binding proteins identified through a string search. J Biol Chem. 2012;287:42071-83 pubmed publisher..We suggest that the clustered SIMs in these proteins form distinct SUMO binding domains to recognize diverse forms of protein sumoylation. ..
- Lin D, Huang Y, Jeng J, Kuo H, Chang C, Chao T, et al. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell. 2006;24:341-54 pubmed..Our results provide mechanistic insights into Daxx in SUMO-dependent transcriptional control and subnuclear compartmentalization. ..
- Reverter D, Lima C. Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates. Nat Struct Mol Biol. 2006;13:1060-8 pubmed..Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing. ..
- Mukhopadhyay D, Arnaoutov A, Dasso M. The SUMO protease SENP6 is essential for inner kinetochore assembly. J Cell Biol. 2010;188:681-92 pubmed publisher..Together, these findings reveal a novel mechanism whereby the finely balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components. ..
- Matic I, van Hagen M, Schimmel J, Macek B, Ogg S, Tatham M, et al. In vivo identification of human small ubiquitin-like modifier polymerization sites by high accuracy mass spectrometry and an in vitro to in vivo strategy. Mol Cell Proteomics. 2008;7:132-44 pubmed publisher..The developed methodology is generic and can be adapted for the identification of other sumoylation sites in complex samples. ..
- Stehmeier P, Muller S. Phospho-regulated SUMO interaction modules connect the SUMO system to CK2 signaling. Mol Cell. 2009;33:400-9 pubmed publisher..We provide evidence that the phosphorylated residues contact lysine 39 and 35 in SUMO1 and SUMO2, respectively...
- Kamitani T, Nguyen H, Kito K, Fukuda Kamitani T, Yeh E. Covalent modification of PML by the sentrin family of ubiquitin-like proteins. J Biol Chem. 1998;273:3117-20 pubmed..Thus differential sentrinization of PML and PML-RARalpha could play an important role in regulating the biological function of PML and in the pathogenesis of acute promyelocytic leukemia. ..
- Fu C, Ahmed K, Ding H, Ding X, Lan J, Yang Z, et al. Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3. Oncogene. 2005;24:5401-13 pubmed..Taken together, our studies provide first line of evidence showing that SUMO-3 is essential for PML localization and offer novel insight into the pathobiochemistry of APL...
- Ihara M, Koyama H, Uchimura Y, Saitoh H, Kikuchi A. Noncovalent binding of small ubiquitin-related modifier (SUMO) protease to SUMO is necessary for enzymatic activities and cell growth. J Biol Chem. 2007;282:16465-75 pubmed..These results indicate that the noncovalent binding of SUMO protease to SUMO through salt bridge is essential for the enzymatic activities and that the balance between sumoylation and desumoylation is important for cell growth control. ..
- Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R. PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev. 2001;15:3088-103 pubmed..Moreover, PIASy binds to nuclear matrix-associated DNA sequences and targets LEF1 to nuclear bodies, suggesting that PIASy-mediated subnuclear sequestration accounts for the repression of LEF1 activity. ..
- Cuchet Lourenço D, Boutell C, Lukashchuk V, Grant K, Sykes A, Murray J, et al. SUMO pathway dependent recruitment of cellular repressors to herpes simplex virus type 1 genomes. PLoS Pathog. 2011;7:e1002123 pubmed publisher..We conclude that recruitment of ND10 components to sites associated with HSV-1 genomes reflects a cellular defence against invading pathogen DNA that is regulated through the SUMO modification pathway. ..
- Escobar Cabrera E, Okon M, Lau D, Dart C, Bonvin A, McIntosh L. Characterizing the N- and C-terminal Small ubiquitin-like modifier (SUMO)-interacting motifs of the scaffold protein DAXX. J Biol Chem. 2011;286:19816-29 pubmed publisher..These results provide insights into the binding mechanisms and hence biological roles of the DAXX SUMO-interacting motifs. ..
- Meulmeester E, Kunze M, Hsiao H, Urlaub H, Melchior F. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell. 2008;30:610-9 pubmed publisherVertebrates express two distinct families of SUMO proteins (SUMO1 and SUMO2/3) that serve distinct functions as posttranslational modifiers...
- Tatham M, Matic I, Mann M, Hay R. Comparative proteomic analysis identifies a role for SUMO in protein quality control. Sci Signal. 2011;4:rs4 pubmed publisher..Together, these findings suggest multiple, proteasome-independent roles for SUMOs in the cellular response to the accumulation of misfolded proteins. ..
- Brunet Simioni M, de Thonel A, Hammann A, Joly A, Bossis G, Fourmaux E, et al. Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity. Oncogene. 2009;28:3332-44 pubmed publisher..As we also show that HSP27 binds to the SUMO-E2-conjugating enzyme, Ubc9, our study raises the possibility that HSP27 may act as a SUMO-E3 ligase specific for SUMO-2/3. ..
- Rosendorff A, Sakakibara S, Lu S, Kieff E, Xuan Y, DiBacco A, et al. NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression. Proc Natl Acad Sci U S A. 2006;103:5308-13 pubmed..SUMO-2-associated proteins identified in this study may contribute to SUMO-dependent regulation of transcription or other processes. ..
- Xu Z, Au S. Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1. Biochem J. 2005;386:325-30 pubmed..Taken together, we suggest that the observed differential maturation process has its physiological significance in the regulation of the sumoylation pathway. ..
- Vertegaal A, Ogg S, Jaffray E, Rodriguez M, Hay R, Andersen J, et al. A proteomic study of SUMO-2 target proteins. J Biol Chem. 2004;279:33791-8 pubmed..SART1 and heterogeneous nuclear RNP M were both shown to be genuine SUMO targets, confirming the validity of the approach. ..
- Golebiowski F, Matic I, Tatham M, Cole C, Yin Y, Nakamura A, et al. System-wide changes to SUMO modifications in response to heat shock. Sci Signal. 2009;2:ra24 pubmed publisher..This comprehensive proteomic analysis of the substrates of a ubiquitin-like modifier (Ubl) identifies a pervasive role for SUMO proteins in the biologic response to hyperthermic stress. ..
- Schimmel J, Larsen K, Matic I, van Hagen M, Cox J, Mann M, et al. The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle. Mol Cell Proteomics. 2008;7:2107-22 pubmed publisher..We conclude that SUMO-2/3 conjugation and the ubiquitin-proteasome system are tightly integrated and act in a cooperative manner. ..
- Bruderer R, Tatham M, Plechanovova A, Matic I, Garg A, Hay R. Purification and identification of endogenous polySUMO conjugates. EMBO Rep. 2011;12:142-8 pubmed publisher..We use this approach to identify more than 300 putative polySUMO conjugates from cultured eukaryotic cells. ..
- Han Y, Huang C, Sun X, Xiang B, Wang M, Yeh E, et al. SENP3-mediated de-conjugation of SUMO2/3 from promyelocytic leukemia is correlated with accelerated cell proliferation under mild oxidative stress. J Biol Chem. 2010;285:12906-15 pubmed publisher..However, whether and how SUMO2/3-specific proteases are involved in de-conjugation under cell stress is unclear...
- MacPherson M, Beatty L, Zhou W, Du M, Sadowski P. The CTCF insulator protein is posttranslationally modified by SUMO. Mol Cell Biol. 2009;29:714-25 pubmed publisher..These studies expand the repertoire of posttranslational modifications of CTCF and suggest roles for such modifications in its regulation of epigenetic states. ..
- Saitoh H, Hinchey J. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. J Biol Chem. 2000;275:6252-8 pubmed..The functions and regulation of these proteins, known as SUMO-2/SMT3A and SUMO-3/SMT3B, remain largely uncharacterized...
- Tatham M, Jaffray E, Vaughan O, Desterro J, Botting C, Naismith J, et al. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001;276:35368-74 pubmed..Although SUMO-2/SMT3A/Sentrin-3 and SUMO-3/SMT3B/Sentrin-2 share 50% sequence identity with SUMO-1, they are functionally distinct...
- Castillo Lluva S, Tatham M, Jones R, Jaffray E, Edmondson R, Hay R, et al. SUMOylation of the GTPase Rac1 is required for optimal cell migration. Nat Cell Biol. 2010;12:1078-85 pubmed publisher..The finding that a Ras superfamily member can be SUMOylated provides an insight into the regulation of these critical mediators of cell behaviour. Our data reveal a role for SUMO in the regulation of cell migration and invasion. ..
- Matic I, Schimmel J, Hendriks I, van Santen M, van de Rijke F, van Dam H, et al. Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif. Mol Cell. 2010;39:641-52 pubmed publisher..In 16 proteins we identified a hydrophobic cluster SUMOylation motif (HCSM). SUMO conjugation of RanGAP1 and ZBTB1 via HCSMs is remarkably efficient. ..
- Gregoire S, Tremblay A, Xiao L, Yang Q, Ma K, Nie J, et al. Control of MEF2 transcriptional activity by coordinated phosphorylation and sumoylation. J Biol Chem. 2006;281:4423-33 pubmed
- de La Vega L, Fröbius K, Moreno R, Calzado M, Geng H, Schmitz M. Control of nuclear HIPK2 localization and function by a SUMO interaction motif. Biochim Biophys Acta. 2011;1813:283-97 pubmed publisher..HIPK2 mutants with an inactive SIM showed changed activities, thus revealing that non-covalent binding of SUMO to the kinase is important for the regulation of its function. ..
- Sramko M, Markus J, Kabat J, Wolff L, Bies J. Stress-induced inactivation of the c-Myb transcription factor through conjugation of SUMO-2/3 proteins. J Biol Chem. 2006;281:40065-75 pubmed..Our findings demonstrate that SUMO-2/3 proteins conjugate to c-Myb and negatively regulate its activity in cells under stress. ..
- Guzzo C, Berndsen C, Zhu J, Gupta V, Datta A, Greenberg R, et al. RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage. Sci Signal. 2012;5:ra88 pubmed publisher..Our findings, therefore, connect ubiquitin- and SUMO-dependent DSB recognition, revealing that RNF4-synthesized hybrid SUMO-ubiquitin chains are recognized by RAP80 to promote BRCA1 recruitment and DNA repair. ..
- Weisshaar S, Keusekotten K, Krause A, Horst C, Springer H, Göttsche K, et al. Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML. FEBS Lett. 2008;582:3174-8 pubmed publisher..Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4. ..
- Janer A, Werner A, Takahashi Fujigasaki J, Daret A, Fujigasaki H, Takada K, et al. SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7. Hum Mol Genet. 2010;19:181-95 pubmed publisher..Expansion of the polyglutamine stretch did not impair the SUMOylation of ATXN7. Furthermore, SUMO1 and SUMO2 colocalized with ATXN7 in a subset of neuronal intranuclear inclusions in the brain of SCA7 patients and SCA7 ..
- Yin Y, Seifert A, Chua J, Maure J, Golebiowski F, Hay R. SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage. Genes Dev. 2012;26:1196-208 pubmed publisher..Thus, RNF4 is a novel DNA damage-responsive protein that plays a role in homologous recombination and integrates SUMO modification and ubiquitin signaling in the cellular response to genotoxic stress. ..