Small ubiquitin-related modifier 1

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Small ubiquitin-like modifier 1
Protein SUMO1 PDB 1a5r.png
PDB rendering based on 1a5r.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols SUMO1 ; DAP1; GMP1; OFC10; PIC1; SENP2; SMT3; SMT3C; SMT3H3; UBL1
External IDs OMIM601912 MGI1197010 HomoloGene2514 GeneCards: SUMO1 Gene
RNA expression pattern
PBB GE SUMO1 208761 s at tn.png
PBB GE SUMO1 208762 at tn.png
PBB GE SUMO1 211069 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7341 22218
Ensembl ENSG00000116030 ENSMUSG00000026021
UniProt P63165 P63166
RefSeq (mRNA) NM_001005781 NM_009460
RefSeq (protein) NP_001005781 NP_033486
Location (UCSC) Chr 2:
202.21 – 202.24 Mb
Chr 1:
59.59 – 59.67 Mb
PubMed search [1] [2]

Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the SUMO1 gene.[1][2]

This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin, which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized.[3]

Most cleft genes have a sumoylation component .[4] Analysis of chromosomal anomalies in patients has led to the identification and confirmation of SUMO1 as a cleft lip and palate locus.[5]


Small ubiquitin-related modifier 1 has been shown to interact with SAE2,[6][7] Death-associated protein 6,[8][9][10] Fas receptor,[2][9] Sp1 transcription factor,[11] PIAS1,[12][13] Thymine-DNA glycosylase,[14][15] UBE2I,[6][14][16][17] TNFRSF1A,[2][18] P53,[10][14] TOP2B,[19] TOP2A,[19] DNMT3B,[20] Promyelocytic leukemia protein,[8][21] and C22orf25.[22]

SUMO1 Role in the Heart[edit]

Heart failure is a process by which the heart’s pumping ability is significantly weakened, so that the body is unable to get adequate circulation. A weakened heart results in symptoms of fatigue, decreased exercise tolerance and shortness of breath. Patients with heart failure have a significantly increased risk of death compared to people with normal heart function. Heart failure is a major public health concern, as its incidence is on the rise worldwide, and is a leading cause of death in developed nations [23]

SUMO 1 is a key component in cardiac function, since it helps regulate calcium homeostasis in the mitochondria of heart cells. SUMO 1 is associated with another essential cardiac protein called sarco/endoplasmic reticulum Ca2+ ATPase, or SERCA2A. SERCA is a transmembrane protein located in the sarcoplasmic reticulum of cardiac cells. Its main function is to regulate the discharge and uptake of intracellular calcium between the cytosol and the lumen of the sarcoplasmic reticulum. Calcium is an essential factor for the development of cardiac myocyte contraction and relaxation. Thus, the management of intracellular calcium homeostasis by SERCA2A is critical for overall cardiac performance.[24] Normally, SUMO 1 activates and stabilizes SERCA2A by binding at lysine resides 480 and 585. The interaction between SUMO 1 and SERCA2A is crucial for regulating calcium levels inside cardiac myocytes. Reduction in SUMO 1 protein reduces SERCA2A, and thus efficient calcium handling in patients with failing hearts [25]

SUMO 1 as a Drug Target[edit]

SUMO 1 may be an important therapeutic target to help improve cardiac performance in patients with heart failure. In a mouse model, the introduction of SUMO 1 through gene therapy was associated with improved activity of SERCA2A, which resulted in improved cardiac function through an augmentation of cardiac contractility.[25] Furthermore, overexpression of SUMO 1 resulted in accelerated calcium uptake, providing further evidence regarding its importance in maintaining adequate calcium levels in heart cells. This particular heart protein may be an exciting and novel target for heart failure treatment in the future.[25]

See also[edit]


  1. ^ Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (January 1997). "UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins". Genomics 36 (2): 271–9. doi:10.1006/geno.1996.0462. PMID 8812453. 
  2. ^ a b c Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ET (Dec 1996). "Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin". J Immunol 157 (10): 4277–81. PMID 8906799.  Cite error: Invalid <ref> tag; name "pmid8906799" defined multiple times with different content (see the help page).
  3. ^ "Entrez Gene: SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)". 
  4. ^ Pauws E, Stanier P (December 2007). "FGF signalling and SUMO modification: new players in the aetiology of cleft lip and/or palate". Trends Genet. 23 (12): 631–40. doi:10.1016/j.tig.2007.09.002. PMID 17981355. 
  5. ^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews Genetics (12) 167-178.
  6. ^ a b Tatham, Michael H; Kim Suhkmann; Yu Bin; Jaffray Ellis; Song Jing; Zheng Jian; Rodriguez Manuel S; Hay Ronald T; Chen Yuan (August 2003). "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry (United States) 42 (33): 9959–69. doi:10.1021/bi0345283. ISSN 0006-2960. PMID 12924945. 
  7. ^ Gong, L; Li B; Millas S; Yeh E T (April 1999). "Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex". FEBS Lett. (NETHERLANDS) 448 (1): 185–9. doi:10.1016/S0014-5793(99)00367-1. ISSN 0014-5793. PMID 10217437. 
  8. ^ a b Lin, Ding-Yen; Shih Hsiu-Ming (July 2002). "Essential role of the 58-kDa microspherule protein in the modulation of Daxx-dependent transcriptional repression as revealed by nucleolar sequestration". J. Biol. Chem. (United States) 277 (28): 25446–56. doi:10.1074/jbc.M200633200. ISSN 0021-9258. PMID 11948183. 
  9. ^ a b Ryu, S W; Chae S K; Kim E (Dec 2000). "Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9". Biochem. Biophys. Res. Commun. (UNITED STATES) 279 (1): 6–10. doi:10.1006/bbrc.2000.3882. ISSN 0006-291X. PMID 11112409. 
  10. ^ a b Ivanchuk, Stacey M; Mondal Soma; Rutka James T (June 2008). "p14ARF interacts with DAXX: effects on HDM2 and p53". Cell Cycle (United States) 7 (12): 1836–50. doi:10.4161/cc.7.12.6025. PMID 18583933. 
  11. ^ Wang, Yi-Ting; Chuang Jian-Ying; Shen Meng-Ru; Yang Wen-Bin; Chang Wen-Chang; Hung Jan-Jong (July 2008). "Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process". J. Mol. Biol. (England) 380 (5): 869–85. doi:10.1016/j.jmb.2008.05.043. PMID 18572193. 
  12. ^ Lee, Byoung-Hee; Yoshimatsu Kumiko; Maeda Akihiko; Ochiai Kazuhiko; Morimatsu Masami; Araki Koichi; Ogino Michiko; Morikawa Shigeru; Arikawa Jiro (Dec 2003). "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules". Virus Res. (Netherlands) 98 (1): 83–91. doi:10.1016/j.virusres.2003.09.001. ISSN 0168-1702. PMID 14609633. 
  13. ^ Kahyo, T; Nishida T; Yasuda H (September 2001). "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Mol. Cell (United States) 8 (3): 713–8. doi:10.1016/S1097-2765(01)00349-5. ISSN 1097-2765. PMID 11583632. 
  14. ^ a b c Minty, A; Dumont X; Kaghad M; Caput D (November 2000). "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif". J. Biol. Chem. (UNITED STATES) 275 (46): 36316–23. doi:10.1074/jbc.M004293200. ISSN 0021-9258. PMID 10961991. 
  15. ^ Hardeland, Ulrike; Steinacher Roland; Jiricny Josef; Schär Primo (March 2002). "Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover". EMBO J. (England) 21 (6): 1456–64. doi:10.1093/emboj/21.6.1456. ISSN 0261-4189. PMC 125358. PMID 11889051. 
  16. ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. 
  17. ^ Shen, Z; Pardington-Purtymun P E; Comeaux J C; Moyzis R K; Chen D J (October 1996). "Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system". Genomics (UNITED STATES) 37 (2): 183–6. doi:10.1006/geno.1996.0540. ISSN 0888-7543. PMID 8921390. 
  18. ^ Liou, M L; Liou H C (April 1999). "The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis". J. Biol. Chem. (UNITED STATES) 274 (15): 10145–53. doi:10.1074/jbc.274.15.10145. ISSN 0021-9258. PMID 10187798. 
  19. ^ a b Mao, Y; Desai S D; Liu L F (August 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". J. Biol. Chem. (UNITED STATES) 275 (34): 26066–73. doi:10.1074/jbc.M001831200. ISSN 0021-9258. PMID 10862613. 
  20. ^ Kang, E S; Park C W; Chung J H (Dec 2001). "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochem. Biophys. Res. Commun. (United States) 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. ISSN 0006-291X. PMID 11735126. 
  21. ^ Kamitani, T; Nguyen H P; Kito K; Fukuda-Kamitani T; Yeh E T (February 1998). "Covalent modification of PML by the sentrin family of ubiquitin-like proteins". J. Biol. Chem. (UNITED STATES) 273 (6): 3117–20. doi:10.1074/jbc.273.6.3117. ISSN 0021-9258. PMID 9452416. 
  22. ^ "Molecular Interaction Database". 
  23. ^ Schwartz, R. J., & Yeh, E. T. (2012). Weighing in on Heart Failure: The Role of SERCA2a SUMOylation. Circulation research, 110(2), 198-199.
  24. ^ Periasamy, M., & Huke, S. (2001). SERCA Pump Level is a Critical Determinant of Ca< sup> 2+ Homeostasis and Cardiac Contractility. Journal of molecular and cellular cardiology, 33(6), 1053-1063.
  25. ^ a b c Kho, C., Lee, A., Jeong, D., Oh, J. G., Chaanine, A. H., Kizana, E., & Hajjar, R. J. (2011). SUMO1-dependent modulation of SERCA2a in heart failure" Nature 477(7366), 601-605.

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