small ubiquitin related modifier proteins


Summary: A class of structurally related proteins of 12-20 kDa in size. They covalently modify specific proteins in a manner analogous to UBIQUITIN.

Top Publications

  1. Park S, Hu X, Gupta P, Lin Y, Ha S, Wei L. SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells. Nat Struct Mol Biol. 2007;14:68-75 pubmed
  2. Ulrich H. The SUMO system: an overview. Methods Mol Biol. 2009;497:3-16 pubmed publisher
    ..This chapter gives a brief overview over the enzymes of the SUMO system, its regulation, and its functions. ..
  3. Cheng C, Lin F, Lo Y, Wang T. Tying SUMO modifications to dynamic behaviors of chromosomes during meiotic prophase of Saccharomyces cerevisiae. J Biomed Sci. 2007;14:481-90 pubmed
    ..This review discusses recent studies related to the role of small ubiquitin-like modifier (SUMO) modification in controlling the overall budding yeast chromosome dynamics during meiotic prophase. ..
  4. Kerscher O. SUMO junction-what's your function? New insights through SUMO-interacting motifs. EMBO Rep. 2007;8:550-5 pubmed
  5. Reverter D, Lima C. Preparation of SUMO proteases and kinetic analysis using endogenous substrates. Methods Mol Biol. 2009;497:225-39 pubmed publisher
    ..We will also describe methods for kinetic analysis of SUMO deconjugation and maturation using endogenous substrates. ..
  6. Wu X, Nie C, Huang Z, Nie Y, Yan Q, Xiao Y, et al. Expression and purification of human keratinocyte growth factor 2 by fusion with SUMO. Mol Biotechnol. 2009;42:68-74 pubmed publisher
    ..9 mg/l culture. The result of mitogenicity assay suggests that the recombinant hKGF-2 can significantly promote the proliferation of normal rat kidney epithelial (NRK-52E) cells. ..
  7. Zhu J, Zhu S, Guzzo C, Ellis N, Sung K, Choi C, et al. Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification. J Biol Chem. 2008;283:29405-15 pubmed publisher
  8. Mullen J, Brill S. Activation of the Slx5-Slx8 ubiquitin ligase by poly-small ubiquitin-like modifier conjugates. J Biol Chem. 2008;283:19912-21 pubmed publisher
    ..Slx5-Slx8 primarily mono-ubiquitinated the N-terminal SUMO moiety of the chain. These data indicate that the Slx5-Slx8 Ub ligase is stimulated by poly-SUMO conjugates and that it can ubiquitinate a poly-SUMO chain. ..
  9. Perry J, Tainer J, Boddy M. A SIM-ultaneous role for SUMO and ubiquitin. Trends Biochem Sci. 2008;33:201-8 pubmed publisher
    ..The human STUbL, RNF4, is implicated in several diseases including cancer, highlighting the importance of characterizing the cellular functions of STUbLs. ..

More Information


  1. Zhang X, Goeres J, Zhang H, Yen T, Porter A, Matunis M. SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis. Mol Cell. 2008;29:729-41 pubmed publisher
    ..Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes. ..
  2. Valin A, Gill G. Regulation of the dual-function transcription factor Sp3 by SUMO. Biochem Soc Trans. 2007;35:1393-6 pubmed
    ..Recent studies to identify additional co-repressors associated with SUMO and further investigate regulated activity of Sp3 are providing a deeper understanding of SUMO-dependent mechanisms of transcriptional regulation. ..
  3. Shalizi A, Bilimoria P, Stegmuller J, Gaudilliere B, Yang Y, Shuai K, et al. PIASx is a MEF2 SUMO E3 ligase that promotes postsynaptic dendritic morphogenesis. J Neurosci. 2007;27:10037-46 pubmed
  4. Eckert Boulet N, Lisby M. Regulation of rDNA stability by sumoylation. DNA Repair (Amst). 2009;8:507-16 pubmed publisher
    ..The relocalization before repair is important for maintaining rDNA stability. The focus of this review is the regulation of recombinational DNA repair at the rDNA locus by sumoylation and the Smc5-Smc6 complex in S. cerevisiae. ..
  5. Rytinki M, Kaikkonen S, Pehkonen P, Jääskeläinen T, Palvimo J. PIAS proteins: pleiotropic interactors associated with SUMO. Cell Mol Life Sci. 2009;66:3029-41 pubmed publisher
    ..Here, we present an overview of the cellular regulation by PIAS proteins and propose that many of their functions are due to their capability to mediate and facilitate SUMO-linked protein assemblies. ..
  6. Wang J, Qin H, Liang J, Zhu Y, Liang L, Zheng M, et al. The transcriptional repression activity of KyoT2 on the Notch/RBP-J pathway is regulated by PIAS1-catalyzed SUMOylation. J Mol Biol. 2007;370:27-38 pubmed
    ..These results suggest that KyoT2 is a substrate of SUMO modification catalyzed by PIAS1, and that SUMOylation may modulate the transcriptional repression effect of KyoT2 on the Notch/RBP-J signaling pathway. ..
  7. Tatham M, Rodriguez M, Xirodimas D, Hay R. Detection of protein SUMOylation in vivo. Nat Protoc. 2009;4:1363-71 pubmed publisher
    ..In preliminary form, this protocol takes 4-5 d to perform, and it can be further elaborated to provide a multi-angled approach to investigate protein conjugation by SUMO. ..
  8. Shen L, Geoffroy M, Jaffray E, Hay R. Characterization of SENP7, a SUMO-2/3-specific isopeptidase. Biochem J. 2009;421:223-30 pubmed publisher
    ..These findings suggest that SENP7 acts as a SUMO-2/3-specific protease that is likely to regulate the metabolism of poly-SUMO-2/3 rather than SUMO-1 conjugation in vivo. ..
  9. Li H, Gao L, Shen Z, Li C, Li K, Li M, et al. Association study of NFKB1 and SUMO4 polymorphisms in Chinese patients with psoriasis vulgaris. Arch Dermatol Res. 2008;300:425-33 pubmed publisher
  10. Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, et al. SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis. Cell Death Differ. 2008;15:739-50 pubmed publisher
    ..We conclude that SENP1 mediates TNF-induced desumoylation and translocation of HIPK1, leading to an enhanced ASK1-dependent apoptosis. ..
  11. Bischof O, Dejean A. SUMO is growing senescent. Cell Cycle. 2007;6:677-81 pubmed
    ..Here, we discuss some of the implications for this novel connection and future directions to study in more detail the importance of the SUMO pathway in senescence and tumorigenesis. ..
  12. 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 publisher
    ..One mechanism for paralog-specific sumoylation may, thus, involve SIM-dependent recruitment of SUMO1 or SUMO2/3 thioester-charged Ubc9 to targets. ..
  13. Wei F, Scholer H, Atchison M. Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. J Biol Chem. 2007;282:21551-60 pubmed
    ..Therefore, sumoylation of Oct4 results in increased stability, DNA binding, and transactivation and provides an important mechanism to regulate Oct4 activity. ..
  14. Zhao J. Sumoylation regulates diverse biological processes. Cell Mol Life Sci. 2007;64:3017-33 pubmed
    ..This paper reviews recent progress in the study of SUMO pathways, substrates, and cellular functions and highlights important findings that have accelerated advances in this study field and link sumoylation to human diseases. ..
  15. 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). ..
  16. Makhnevych T, Sydorskyy Y, Xin X, Srikumar T, Vizeacoumar F, Jeram S, et al. Global map of SUMO function revealed by protein-protein interaction and genetic networks. Mol Cell. 2009;33:124-35 pubmed publisher
  17. Knipscheer P, Flotho A, Klug H, Olsen J, van Dijk W, Fish A, et al. Ubc9 sumoylation regulates SUMO target discrimination. Mol Cell. 2008;31:371-82 pubmed publisher
    ..The crystal structure of sumoylated Ubc9 demonstrates how the newly created binding interface can provide a gain in affinity otherwise provided by E3 ligases. ..
  18. Gao C, Ho C, Reineke E, Lam M, Cheng X, Stanya K, et al. Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear body formation. Mol Cell Biol. 2008;28:5658-67 pubmed publisher
    ..Importantly, HDAC7 knockdown inhibits tumor necrosis factor alpha-induced PML sumoylation and the formation of PML NBs in HUVECs. These results demonstrate a novel function of HDAC7 and provide a regulatory mechanism of PML sumoylation...
  19. Miles W, Jaffray E, Campbell S, Takeda S, Bayston L, Basu S, et al. Medea SUMOylation restricts the signaling range of the Dpp morphogen in the Drosophila embryo. Genes Dev. 2008;22:2578-90 pubmed publisher
    ..Overall, our results identify an unusual strategy for regulating morphogen range that, rather than impacting on the morphogen itself, targets an intracellular transducer...
  20. Zhang F, Mikkonen L, Toppari J, Palvimo J, Thesleff I, Janne O. Sumo-1 function is dispensable in normal mouse development. Mol Cell Biol. 2008;28:5381-90 pubmed publisher
    ..Collectively, our results support the notion that most, if not all, SUMO-1 functions are compensated for in vivo by SUMO-2 and SUMO-3. ..
  21. Hwang E, Lee J, Jeong J, Park J, Yang Y, Lim J, et al. SUMOylation of RORalpha potentiates transcriptional activation function. Biochem Biophys Res Commun. 2009;378:513-7 pubmed publisher
    ..SUMOylation-defective mutant form of RORalpha exhibited decreased transcriptional activity on RORalpha-responsive promoters indicating that SUMOylation may positively regulate transcriptional function of RORalpha. ..
  22. Garcia Dominguez M, Reyes J. SUMO association with repressor complexes, emerging routes for transcriptional control. Biochim Biophys Acta. 2009;1789:451-9 pubmed publisher
  23. Guo B, Sharrocks A. Extracellular signal-regulated kinase mitogen-activated protein kinase signaling initiates a dynamic interplay between sumoylation and ubiquitination to regulate the activity of the transcriptional activator PEA3. Mol Cell Biol. 2009;29:3204-18 pubmed publisher
  24. Ohuchi T, Seki M, Branzei D, Maeda D, Ui A, Ogiwara H, et al. Rad52 sumoylation and its involvement in the efficient induction of homologous recombination. DNA Repair (Amst). 2008;7:879-89 pubmed publisher
  25. Blomster H, Hietakangas V, Wu J, Kouvonen P, Hautaniemi S, Sistonen L. Novel proteomics strategy brings insight into the prevalence of SUMO-2 target sites. Mol Cell Proteomics. 2009;8:1382-90 pubmed publisher
    ..Given that different types of motifs are bound by Ubc9 using alternative mechanisms, our data suggest that the preference of SUMO-2 targeting mechanism depends on the biological function of the substrate. ..
  26. Hay R. SUMO-specific proteases: a twist in the tail. Trends Cell Biol. 2007;17:370-6 pubmed
    ..Processing of SUMO precursors is mediated by SUMO-specific proteases that also remove SUMO from modified proteins and depolymerise poly-SUMO chains. ..
  27. Haindl M, Harasim T, Eick D, Muller S. The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing. EMBO Rep. 2008;9:273-9 pubmed publisher
    ..These results define SENP3 as an essential factor for ribosome biogenesis and suggest that deconjugation of SUMO2 from NPM1 by SENP3 is critically involved in 28S rRNA maturation. ..
  28. Sun Z, Xia Z, Bi F, Liu J. Expression and purification of human urodilatin by small ubiquitin-related modifier fusion in Escherichia coli. Appl Microbiol Biotechnol. 2008;78:495-502 pubmed publisher
    ..77+/-0.53 microg/ml, which was similar to that of the synthetic urodilatin standard. The expression strategy presented in this study allows convenient high yield and easy purification of small recombinant peptides with native sequences. ..
  29. Xu J, He Y, Qiang B, Yuan J, Peng X, Pan X. A novel method for high accuracy sumoylation site prediction from protein sequences. BMC Bioinformatics. 2008;9:8 pubmed publisher
    ..By using a statistical method, we have developed a new SUMO site prediction method - SUMOpre, which has shown its great accuracy with correlation coefficient, specificity, sensitivity and accuracy. ..
  30. 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. ..
  31. Guo B, Yang S, Witty J, Sharrocks A. Signalling pathways and the regulation of SUMO modification. Biochem Soc Trans. 2007;35:1414-8 pubmed
    ..Further intricacies in signalling pathway interactions are hinted at through the growing number of examples of cross-talk between different post-translational modifications and SUMO modification. ..
  32. Chao H, Hong C, Huang T, Lin Y, Hsueh Y. SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis. J Cell Biol. 2008;182:141-55 pubmed publisher
    ..1. Overexpression of a CASK-SUMO1 fusion construct, which mimicks CASK SUMOylation, impairs spine formation. Our study suggests that CASK contributes to spinogenesis and that this is controlled by SUMOylation. ..
  33. Geiss Friedlander R, Melchior F. Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol. 2007;8:947-56 pubmed
    ..At first glance, these effects have nothing in common; however, it seems that they all result from changes in the molecular interactions of the sumoylated proteins. ..
  34. 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. ..
  35. Siatecka M, Xue L, Bieker J. Sumoylation of EKLF promotes transcriptional repression and is involved in inhibition of megakaryopoiesis. Mol Cell Biol. 2007;27:8547-60 pubmed
    ..These studies demonstrate a novel mechanism by which transcription factor sumoylation can alter protein-protein interactions and bipotential lineage decisions. ..
  36. Lee H, Johnson K, Fujiwara T, Boyer M, Kim S, Bresnick E. Controlling hematopoiesis through sumoylation-dependent regulation of a GATA factor. Mol Cell. 2009;36:984-95 pubmed publisher
    ..These results illustrate a mechanism that controls trans-acting factor function in a locus-specific manner, and differentially regulated members of the target gene ensemble reside in distinct subnuclear compartments. ..
  37. Burgess R, Rahman S, Lisby M, Rothstein R, Zhao X. The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol Cell Biol. 2007;27:6153-62 pubmed
    ..In addition, the complex inhibits Rad51-independent recombination via modulating the sumoylation of DNA repair proteins. ..
  38. Xhemalce B, Riising E, Baumann P, Dejean A, Arcangioli B, Seeler J. Role of SUMO in the dynamics of telomere maintenance in fission yeast. Proc Natl Acad Sci U S A. 2007;104:893-8 pubmed
    ..Instead, sumoylation increases telomerase activity, therefore suggesting that this modification controls the activity of a positive or negative regulator of telomerase. ..
  39. Oshima M, Mimura J, Sekine H, Okawa H, Fujii Kuriyama Y. SUMO modification regulates the transcriptional repressor function of aryl hydrocarbon receptor repressor. J Biol Chem. 2009;284:11017-26 pubmed publisher
    ..AhRR, but not AhR, also significantly enhanced the SUMOylation of Arnt. The SUMOylation of both AhRR and Arnt is important for the efficient transcriptional repression activity of the AhRR/Arnt heterodimer. ..
  40. Huang Y, Su Z, Li Y, Zhang Q, Cui L, Su Y, et al. Expression and Purification of glutathione transferase-small ubiquitin-related modifier-metallothionein fusion protein and its neuronal and hepatic protection against D-galactose-induced oxidative damage in mouse model. J Pharmacol Exp Ther. 2009;329:469-78 pubmed publisher
    ..Therefore, GST-SUMO-MT may be a potential candidate to be developed for the clinical application. ..
  41. Meulmeester E, Melchior F. Cell biology: SUMO. Nature. 2008;452:709-11 pubmed publisher
  42. Yang Y, Fu W, Chen J, Olashaw N, Zhang X, Nicosia S, et al. SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress. Nat Cell Biol. 2007;9:1253-62 pubmed
  43. Prudden J, Pebernard S, Raffa G, Slavin D, Perry J, Tainer J, et al. SUMO-targeted ubiquitin ligases in genome stability. EMBO J. 2007;26:4089-101 pubmed
    ..The DNA repair factor Rad60 and its human homolog NIP45, which contain SLDs, are candidate STUbL targets. Consistently, Rad60 and Slx8-Rfp mutants have similar DNA repair defects. ..
  44. Sun H, Leverson J, Hunter T. Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins. EMBO J. 2007;26:4102-12 pubmed
    ..Hence, we describe a family of SIM-containing RING-finger proteins that potentially regulates eukaryotic genome stability through linking SUMO-interaction with ubiquitin conjugation. ..
  45. Mukhopadhyay D, Dasso M. Modification in reverse: the SUMO proteases. Trends Biochem Sci. 2007;32:286-95 pubmed
    ..The dissimilar sub-nuclear localization patterns of Ulp/SENPs and phenotypes of Ulp/SENP mutants further indicate that different Ulp/SENPs have distinct and non-redundant roles. ..
  46. Duda D, van Waardenburg R, Borg L, McGarity S, Nourse A, Waddell M, et al. Structure of a SUMO-binding-motif mimic bound to Smt3p-Ubc9p: conservation of a non-covalent ubiquitin-like protein-E2 complex as a platform for selective interactions within a SUMO pathway. J Mol Biol. 2007;369:619-30 pubmed
    ..The results imply that non-covalent ubiquitin-like protein-E2 complexes are conserved platforms, which function as parts of larger assemblies involved in many protein post-translational regulatory pathways. ..
  47. Chinnadurai G. Transcriptional regulation by C-terminal binding proteins. Int J Biochem Cell Biol. 2007;39:1593-607 pubmed
    ..The nuclear dinucleotide ratio may differentially influence the repression activities of factors that recruit CtBP through PLDLS-like motifs and those through non-PLDLS-motifs. ..
  48. Wei W, Yang P, Pang J, Zhang S, Wang Y, Wang M, et al. A stress-dependent SUMO4 sumoylation of its substrate proteins. Biochem Biophys Res Commun. 2008;375:454-9 pubmed publisher
    ..These data not only confirmed our previous published data, but also provided additional evidence suggesting a role for SUMO4 sumoylation in the regulation of intracellular stress. ..
  49. Martin S, Wilkinson K, Nishimune A, Henley J. Emerging extranuclear roles of protein SUMOylation in neuronal function and dysfunction. Nat Rev Neurosci. 2007;8:948-59 pubmed
  50. Jakobs A, Himstedt F, Funk M, Korn B, Gaestel M, Niedenthal R. Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation. Nucleic Acids Res. 2007;35:e109 pubmed
    ..Hence, UFDS is appropriate for the identification and characterization of constitutive and, more importantly, induced protein SUMOylation in vivo. ..
  51. Ren G, Hou Y, Jiang Y, Li J, Zhang W, Di L, et al. [Efficient expression of soluble human FGF-21 and its glucose regulation activity]. Yao Xue Xue Bao. 2009;44:548-52 pubmed
    ..Compared with no stimulation control, the recombinant hFGF-21 treatment led to a significant increase in glucose consumption of adipocytes and a significant decrease in concentration of glucose in the medium (P < 0.05, P < 0.001). ..
  52. Noso S, Fujisawa T, Kawabata Y, Asano K, Hiromine Y, Fukai A, et al. Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J Clin Endocrinol Metab. 2007;92:2358-62 pubmed
    ..24; 95% CI, 0.81-1.89; not significant). These data, together with previous reports, suggest the contribution of the SUMO4 Met55Val polymorphism to both type 1 and type 2 diabetes susceptibility in the Japanese population. ..
  53. 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. ..