Biology:SUMO1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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

Function

This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein and 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 is primarily associated with targeting proteins for proteasomal degradation, SUMO1 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]

Interactions

Small ubiquitin-related modifier 1 has been shown to interact with:


Role in the heart

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]

As a drug target

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.[25]

See also

  • SENP6

References

  1. ↑ "UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins". Genomics 36 (2): 271–9. September 1996. doi:10.1006/geno.1996.0462. PMID 8812453. https://zenodo.org/record/1229737. 
  2. ↑ 2.0 2.1 2.2 "Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin". Journal of Immunology 157 (10): 4277–81. November 1996. doi:10.4049/jimmunol.157.10.4277. PMID 8906799. 
  3. ↑ "Entrez Gene: SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7341. 
  4. ↑ "FGF signalling and SUMO modification: new players in the aetiology of cleft lip and/or palate". Trends in Genetics 23 (12): 631–40. December 2007. 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. ↑ "Molecular Interaction Database". http://mint.bio.uniroma2.it/mint/Welcome.do. 
  7. ↑ 7.0 7.1 "Essential role of the 58-kDa microspherule protein in the modulation of Daxx-dependent transcriptional repression as revealed by nucleolar sequestration". The Journal of Biological Chemistry 277 (28): 25446–56. July 2002. doi:10.1074/jbc.M200633200. PMID 11948183. 
  8. ↑ 8.0 8.1 "Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9". Biochemical and Biophysical Research Communications 279 (1): 6–10. December 2000. doi:10.1006/bbrc.2000.3882. PMID 11112409. 
  9. ↑ 9.0 9.1 "p14ARF interacts with DAXX: effects on HDM2 and p53". Cell Cycle 7 (12): 1836–50. June 2008. doi:10.4161/cc.7.12.6025. PMID 18583933. 
  10. ↑ "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochemical and Biophysical Research Communications 289 (4): 862–8. December 2001. doi:10.1006/bbrc.2001.6057. PMID 11735126. 
  11. ↑ 11.0 11.1 11.2 "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif". The Journal of Biological Chemistry 275 (46): 36316–23. November 2000. doi:10.1074/jbc.M004293200. PMID 10961991. 
  12. ↑ "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules". Virus Research 98 (1): 83–91. December 2003. doi:10.1016/j.virusres.2003.09.001. PMID 14609633. 
  13. ↑ "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Molecular Cell 8 (3): 713–8. September 2001. doi:10.1016/S1097-2765(01)00349-5. PMID 11583632. 
  14. ↑ "Covalent modification of PML by the sentrin family of ubiquitin-like proteins". The Journal of Biological Chemistry 273 (6): 3117–20. February 1998. doi:10.1074/jbc.273.6.3117. PMID 9452416. 
  15. ↑ 15.0 15.1 "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry 42 (33): 9959–69. August 2003. doi:10.1021/bi0345283. PMID 12924945. 
  16. ↑ "Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex". FEBS Letters 448 (1): 185–9. April 1999. doi:10.1016/S0014-5793(99)00367-1. PMID 10217437. 
  17. ↑ "Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process". Journal of Molecular Biology 380 (5): 869–85. July 2008. doi:10.1016/j.jmb.2008.05.043. PMID 18572193. 
  18. ↑ "Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover". The EMBO Journal 21 (6): 1456–64. March 2002. doi:10.1093/emboj/21.6.1456. PMID 11889051. 
  19. ↑ "The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis". The Journal of Biological Chemistry 274 (15): 10145–53. April 1999. doi:10.1074/jbc.274.15.10145. PMID 10187798. 
  20. ↑ 20.0 20.1 "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry 275 (34): 26066–73. August 2000. doi:10.1074/jbc.M001831200. PMID 10862613. 
  21. ↑ "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931. 
  22. ↑ "Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system". Genomics 37 (2): 183–6. October 1996. doi:10.1006/geno.1996.0540. PMID 8921390. https://zenodo.org/record/1229705. 
  23. ↑ "Weighing in on heart failure: the role of SERCA2a SUMOylation". Circulation Research 110 (2): 198–9. 2012. doi:10.1161/RES.0b013e318246f187. PMID 22267837. 
  24. ↑ "SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac contractility". Journal of Molecular and Cellular Cardiology 33 (6): 1053–63. 2001. doi:10.1006/jmcc.2001.1366. PMID 11444913. 
  25. ↑ 25.0 25.1 25.2 "SUMO1-dependent modulation of SERCA2a in heart failure". Nature 477 (7366): 601–5. 2011. doi:10.1038/nature10407. PMID 21900893. Bibcode: 2011Natur.477..601K. 

Further reading

External links




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