SUMO1
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| Location (UCSC) | Chr 2: 202.21 – 202.24 Mb | Chr 1: 59.63 – 59.71 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the SUMO1 gene.[5][6]
Function
This gene encodes a protein that is a member of the
isoforms have been characterized.[7]
Most
cleft lip and palate locus.[9]
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 [27]
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.[28] 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.[29]
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.[29] Furthermore, overexpression of SUMO 1 resulted in accelerated calcium uptake, providing further evidence regarding its importance in maintaining adequate calcium levels in heart cells.[29]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000116030 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026021 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8812453.
- ^ S2CID 38606511.
- ^ "Entrez Gene: SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)".
- PMID 17981355.
- ^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews Genetics (12) 167-178.
- ^ "Molecular Interaction Database". Archived from the original on 2006-05-06.
- ^ PMID 11948183.
- ^ PMID 11112409.
- ^ PMID 18583933.
- PMID 11735126.
- ^ PMID 10961991.
- PMID 14609633.
- PMID 11583632.
- PMID 9452416.
- ^ PMID 12924945.
- S2CID 7756078.
- PMID 18572193.
- PMID 11889051.
- PMID 10187798.
- ^ PMID 10862613.
- PMID 17353931.
- PMID 8921390.
- PMID 22267837.
- PMID 11444913.
- ^ PMID 21900893.
Further reading
- Cookson MR (January 2003). "Pathways to Parkinsonism". Neuron. 37 (1): 7–10. S2CID 14513509.
- Boddy MN, Howe K, Etkin LD, Solomon E, Freemont PS (September 1996). "PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia". Oncogene. 13 (5): 971–82. PMID 8806687.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (October 1996). "Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system". Genomics. 37 (2): 183–6. PMID 8921390.
- Matunis MJ, Coutavas E, Blobel G (December 1996). "A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex". The Journal of Cell Biology. 135 (6 Pt 1): 1457–70. PMID 8978815.
- Mahajan R, Delphin C, Guan T, Gerace L, Melchior F (January 1997). "A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2". Cell. 88 (1): 97–107. S2CID 17819277.
- Lapenta V, Chiurazzi P, van der Spek P, Pizzuti A, Hanaoka F, Brahe C (March 1997). "SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family". Genomics. 40 (2): 362–6. PMID 9119407.
- Kamitani T, Nguyen HP, Yeh ET (May 1997). "Preferential modification of nuclear proteins by a novel ubiquitin-like molecule". The Journal of Biological Chemistry. 272 (22): 14001–4. PMID 9162015.
- Mahajan R, Gerace L, Melchior F (January 1998). "Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association". The Journal of Cell Biology. 140 (2): 259–70. PMID 9442102.
- Howe K, Williamson J, Boddy N, Sheer D, Freemont P, Solomon E (January 1998). "The ubiquitin-homology gene PIC1: characterization of mouse (Pic1) and human (UBL1) genes and pseudogenes". Genomics. 47 (1): 92–100. PMID 9465300.
- Bayer P, Arndt A, Metzger S, Mahajan R, Melchior F, Jaenicke R, Becker J (July 1998). "Structure determination of the small ubiquitin-related modifier SUMO-1". Journal of Molecular Biology. 280 (2): 275–86. PMID 9654451.
- Desterro JM, Rodriguez MS, Hay RT (August 1998). "SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation". Molecular Cell. 2 (2): 233–9. PMID 9734360.
- Juo P, Kuo CJ, Yuan J, Blenis J (September 1998). "Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade". Current Biology. 8 (18): 1001–8. S2CID 18129508.
- Kamitani T, Kito K, Nguyen HP, Wada H, Fukuda-Kamitani T, Yeh ET (October 1998). "Identification of three major sentrinization sites in PML". The Journal of Biological Chemistry. 273 (41): 26675–82. PMID 9756909.
- Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN, Solomon E, de Thé H, Hay RT, Freemont PS (February 1999). "SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation". Journal of Cell Science. 112 ( Pt 3) (3): 381–93. PMID 9885291.
- Chen A, Mannen H, Li SS (December 1998). "Characterization of mouse ubiquitin-like SMT3A and SMT3B cDNAs and gene/pseudogenes". Biochemistry and Molecular Biology International. 46 (6): 1161–74. S2CID 45939730.
- Okuma T, Honda R, Ichikawa G, Tsumagari N, Yasuda H (January 1999). "In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2". Biochemical and Biophysical Research Communications. 254 (3): 693–8. PMID 9920803.
- Liou ML, Liou HC (April 1999). "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. PMID 10187798.
External links
- SUMO1 human gene location in the UCSC Genome Browser.
- SUMO1 human gene details in the UCSC Genome Browser.
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