Small ubiquitin-related modifier 1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Small ubiquitin-related modifier 1''' is a [[protein]] that in humans is encoded by the ''SUMO1'' [[gene]].<ref name="pmid8812453">{{cite journal | vauthors = Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ | title = UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins | journal = Genomics | volume = 36 | issue = 2 | pages = 271–9 | date = September 1996 | pmid = 8812453 | pmc =  | doi = 10.1006/geno.1996.0462 }}</ref><ref name="pmid8906799">{{cite journal | vauthors = Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ET | title = Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin | journal = Journal of Immunology | volume = 157 | issue = 10 | pages = 4277–81 | date = November 1996 | pmid = 8906799 | pmc = | doi = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_SUMO1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1a5r.
| PDB = {{PDB2|1a5r}}, {{PDB2|1tgz}}, {{PDB2|1wyw}}, {{PDB2|1y8r}}, {{PDB2|1z5s}}, {{PDB2|2asq}}, {{PDB2|2bf8}}, {{PDB2|2g4d}}, {{PDB2|2io2}}, {{PDB2|2iy0}}, {{PDB2|2iy1}}, {{PDB2|2pe6}}
| Name = SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)
| HGNCid = 12502
| Symbol = SUMO1
| AltSymbols =; GMP1; OFC10; PIC1; SENP2; SMT3; SMT3C; SMT3H3; SUMO-1; UBL1
| OMIM = 601912
| ECnumber = 
| Homologene = 2514
| MGIid = 1197010
| GeneAtlas_image1 = PBB_GE_SUMO1_208761_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_SUMO1_208762_at_tn.png
| GeneAtlas_image3 = PBB_GE_SUMO1_211069_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005643 |text = nuclear pore}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006464 |text = protein modification process}} {{GNF_GO|id=GO:0006512 |text = ubiquitin cycle}} {{GNF_GO|id=GO:0016481 |text = negative regulation of transcription}} {{GNF_GO|id=GO:0016925 |text = protein sumoylation}} {{GNF_GO|id=GO:0043433 |text = negative regulation of transcription factor activity}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7341
    | Hs_Ensembl = ENSG00000116030
    | Hs_RefseqProtein = NP_001005781
    | Hs_RefseqmRNA = NM_001005781
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 202779155
    | Hs_GenLoc_end = 202811567
    | Hs_Uniprot = P63165
    | Mm_EntrezGene = 22218
    | Mm_Ensembl = ENSMUSG00000026021
    | Mm_RefseqmRNA = NM_009460
    | Mm_RefseqProtein = NP_033486
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 59584746
    | Mm_GenLoc_end = 59600087
    | Mm_Uniprot = P63166
  }}
}}
'''SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)''', also known as '''SUMO1''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a protein that is a member of the [[SUMO protein|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.<ref name="entrez">{{cite web | title = Entrez Gene: SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7341| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7341| accessdate = }}</ref>
}}


==References==
Most [[Cleft lip and palate|cleft]] genes have a [[sumoylation]] component .<ref>{{cite journal | vauthors = Pauws E, Stanier P | title = FGF signalling and SUMO modification: new players in the aetiology of cleft lip and/or palate | journal = Trends in Genetics | volume = 23 | issue = 12 | pages = 631–40 | date = December 2007 | pmid = 17981355 | doi = 10.1016/j.tig.2007.09.002 }}</ref> Analysis of chromosomal anomalies in patients has led to the identification and confirmation of SUMO1 as a [[cleft lip and palate]] locus.<ref>Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". ''Nature Reviews Genetics'' (12)  167-178.</ref>
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Cookson MR |title=Pathways to Parkinsonism. |journal=Neuron |volume=37 |issue= 1 |pages= 7-10 |year= 2003 |pmid= 12526767 |doi=  }}
*{{cite journal  | author=Boddy MN, Howe K, Etkin LD, ''et al.'' |title=PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia. |journal=Oncogene |volume=13 |issue= 5 |pages= 971-82 |year= 1996 |pmid= 8806687 |doi=  }}
*{{cite journal | author=Shen Z, Pardington-Purtymun PE, Comeaux JC, ''et al.'' |title=UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. |journal=Genomics |volume=36 |issue= 2 |pages= 271-9 |year= 1997 |pmid= 8812453 |doi= 10.1006/geno.1996.0462 }}
*{{cite journal  | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi=  }}
*{{cite journal  | author=Okura T, Gong L, Kamitani T, ''et al.'' |title=Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin. |journal=J. Immunol. |volume=157 |issue= 10 |pages= 4277-81 |year= 1996 |pmid= 8906799 |doi=  }}
*{{cite journal | author=Shen Z, Pardington-Purtymun PE, Comeaux JC, ''et al.'' |title=Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system. |journal=Genomics |volume=37 |issue= 2 |pages= 183-6 |year= 1997 |pmid= 8921390 |doi= 10.1006/geno.1996.0540 }}
*{{cite journal  | author=Matunis MJ, Coutavas E, Blobel G |title=A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. |journal=J. Cell Biol. |volume=135 |issue= 6 Pt 1 |pages= 1457-70 |year= 1997 |pmid= 8978815 |doi=  }}
*{{cite journal  | author=Mahajan R, Delphin C, Guan T, ''et al.'' |title=A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. |journal=Cell |volume=88 |issue= 1 |pages= 97-107 |year= 1997 |pmid= 9019411 |doi=  }}
*{{cite journal  | author=Lapenta V, Chiurazzi P, van der Spek P, ''et al.'' |title=SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family. |journal=Genomics |volume=40 |issue= 2 |pages= 362-6 |year= 1997 |pmid= 9119407 |doi= 10.1006/geno.1996.4556 }}
*{{cite journal  | author=Kamitani T, Nguyen HP, Yeh ET |title=Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. |journal=J. Biol. Chem. |volume=272 |issue= 22 |pages= 14001-4 |year= 1997 |pmid= 9162015 |doi=  }}
*{{cite journal  | author=Mahajan R, Gerace L, Melchior F |title=Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. |journal=J. Cell Biol. |volume=140 |issue= 2 |pages= 259-70 |year= 1998 |pmid= 9442102 |doi=  }}
*{{cite journal  | author=Howe K, Williamson J, Boddy N, ''et al.'' |title=The ubiquitin-homology gene PIC1: characterization of mouse (Pic1) and human (UBL1) genes and pseudogenes. |journal=Genomics |volume=47 |issue= 1 |pages= 92-100 |year= 1998 |pmid= 9465300 |doi= 10.1006/geno.1997.5091 }}
*{{cite journal  | author=Bayer P, Arndt A, Metzger S, ''et al.'' |title=Structure determination of the small ubiquitin-related modifier SUMO-1. |journal=J. Mol. Biol. |volume=280 |issue= 2 |pages= 275-86 |year= 1998 |pmid= 9654451 |doi= 10.1006/jmbi.1998.1839 }}
*{{cite journal  | author=Desterro JM, Rodriguez MS, Hay RT |title=SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. |journal=Mol. Cell |volume=2 |issue= 2 |pages= 233-9 |year= 1998 |pmid= 9734360 |doi=  }}
*{{cite journal  | author=Juo P, Kuo CJ, Yuan J, Blenis J |title=Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. |journal=Curr. Biol. |volume=8 |issue= 18 |pages= 1001-8 |year= 1998 |pmid= 9740801 |doi=  }}
*{{cite journal  | author=Kamitani T, Kito K, Nguyen HP, ''et al.'' |title=Identification of three major sentrinization sites in PML. |journal=J. Biol. Chem. |volume=273 |issue= 41 |pages= 26675-82 |year= 1998 |pmid= 9756909 |doi=  }}
*{{cite journal  | author=Duprez E, Saurin AJ, Desterro JM, ''et al.'' |title=SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation. |journal=J. Cell. Sci. |volume=112 ( Pt 3) |issue=  |pages= 381-93 |year= 1999 |pmid= 9885291 |doi=  }}
*{{cite journal | author=Chen A, Mannen H, Li SS |title=Characterization of mouse ubiquitin-like SMT3A and SMT3B cDNAs and gene/pseudogenes. |journal=Biochem. Mol. Biol. Int. |volume=46 |issue= 6 |pages= 1161-74 |year= 1999 |pmid= 9891849 |doi=  }}
*{{cite journal  | author=Okuma T, Honda R, Ichikawa G, ''et al.'' |title=In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2. |journal=Biochem. Biophys. Res. Commun. |volume=254 |issue= 3 |pages= 693-8 |year= 1999 |pmid= 9920803 |doi= 10.1006/bbrc.1998.9995 }}
*{{cite journal  | author=Liou ML, Liou HC |title=The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis. |journal=J. Biol. Chem. |volume=274 |issue= 15 |pages= 10145-53 |year= 1999 |pmid= 10187798 |doi=  }}
}}
{{refend}}


{{protein-stub}}
== Interactions ==
{{WikiDoc Sources}}
Small ubiquitin-related modifier 1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[C22orf25]],<ref>{{cite web|title=Molecular Interaction Database|url=http://mint.bio.uniroma2.it/mint/Welcome.do}}</ref>
* [[Death-associated protein 6|DAXX]],<ref name=pmid11948183>{{cite journal | vauthors = Lin DY, Shih HM | title = Essential role of the 58-kDa microspherule protein in the modulation of Daxx-dependent transcriptional repression as revealed by nucleolar sequestration | journal = The Journal of Biological Chemistry | volume = 277 | issue = 28 | pages = 25446–56 | date = July 2002 | pmid = 11948183 | doi = 10.1074/jbc.M200633200 }}</ref><ref name=pmid11112409>{{cite journal | vauthors = Ryu SW, Chae SK, Kim E | title = Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9 | journal = Biochemical and Biophysical Research Communications | volume = 279 | issue = 1 | pages = 6–10 | date = December 2000 | pmid = 11112409 | doi = 10.1006/bbrc.2000.3882 }}</ref><ref name=pmid18583933>{{cite journal | vauthors = Ivanchuk SM, Mondal S, Rutka JT | title = p14ARF interacts with DAXX: effects on HDM2 and p53 | journal = Cell Cycle | volume = 7 | issue = 12 | pages = 1836–50 | date = June 2008 | pmid = 18583933 | doi = 10.4161/cc.7.12.6025 }}</ref>
* [[DNMT3B]],<ref name=pmid11735126>{{cite journal | vauthors = Kang ES, Park CW, Chung JH | title = Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1 | journal = Biochemical and Biophysical Research Communications | volume = 289 | issue = 4 | pages = 862–8 | date = December 2001 | pmid = 11735126 | doi = 10.1006/bbrc.2001.6057 }}</ref>
* [[P53]],<ref name=pmid18583933/><ref name=pmid10961991/>
* [[PIAS1]],<ref name=pmid14609633>{{cite journal | vauthors = Lee BH, Yoshimatsu K, Maeda A, Ochiai K, Morimatsu M, Araki K, Ogino M, Morikawa S, Arikawa J | title = Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules | journal = Virus Research | volume = 98 | issue = 1 | pages = 83–91 | date = December 2003 | pmid = 14609633 | doi = 10.1016/j.virusres.2003.09.001 }}</ref><ref name=pmid11583632>{{cite journal | vauthors = Kahyo T, Nishida T, Yasuda H | title = Involvement of PIAS1 in the sumoylation of tumor suppressor p53 | journal = Molecular Cell | volume = 8 | issue = 3 | pages = 713–8 | date = September 2001 | pmid = 11583632 | doi = 10.1016/S1097-2765(01)00349-5 }}</ref>
* [[Promyelocytic leukemia protein|PML]],<ref name=pmid11948183/><ref name=pmid9452416>{{cite journal | vauthors = Kamitani T, Nguyen HP, Kito K, Fukuda-Kamitani T, Yeh ET | title = Covalent modification of PML by the sentrin family of ubiquitin-like proteins | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3117–20 | date = February 1998 | pmid = 9452416 | doi = 10.1074/jbc.273.6.3117 }}</ref>
* [[SAE2]],<ref name=pmid12924945>{{cite journal | vauthors = Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y | title = Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation | journal = Biochemistry | volume = 42 | issue = 33 | pages = 9959–69 | date = August 2003 | pmid = 12924945 | doi = 10.1021/bi0345283 }}</ref><ref name=pmid10217437>{{cite journal | vauthors = Gong L, Li B, Millas S, Yeh ET | title = Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex | journal = FEBS Letters | volume = 448 | issue = 1 | pages = 185–9 | date = April 1999 | pmid = 10217437 | doi = 10.1016/S0014-5793(99)00367-1 }}</ref>
* [[Sp1 transcription factor|SP1]],<ref name=pmid18572193>{{cite journal | vauthors = Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC, Hung JJ | title = Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process | journal = Journal of Molecular Biology | volume = 380 | issue = 5 | pages = 869–85 | date = July 2008 | pmid = 18572193 | doi = 10.1016/j.jmb.2008.05.043 }}</ref>
* [[Thymine-DNA glycosylase|TDG]],<ref name=pmid10961991>{{cite journal | vauthors = Minty A, Dumont X, Kaghad M, Caput D | title = Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif | journal = The Journal of Biological Chemistry | volume = 275 | issue = 46 | pages = 36316–23 | date = November 2000 | pmid = 10961991 | doi = 10.1074/jbc.M004293200 }}</ref><ref name=pmid11889051>{{cite journal | vauthors = Hardeland U, Steinacher R, Jiricny J, Schär P | title = Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover | journal = The EMBO Journal | volume = 21 | issue = 6 | pages = 1456–64 | date = March 2002 | pmid = 11889051 | pmc = 125358 | doi = 10.1093/emboj/21.6.1456 }}</ref>
* [[TNFRSF1A]],<ref name=pmid8906799/><ref name=pmid10187798>{{cite journal | vauthors = Liou ML, Liou HC | title = The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 10145–53 | date = April 1999 | pmid = 10187798 | doi = 10.1074/jbc.274.15.10145 }}</ref>
* [[Fas receptor|TNFRSF6]],<ref name=pmid8906799/><ref name=pmid11112409/>
* [[TOP2A]],<ref name=pmid10862613/>
* [[TOP2B]],<ref name=pmid10862613>{{cite journal | vauthors = Mao Y, Desai SD, Liu LF | title = SUMO-1 conjugation to human DNA topoisomerase II isozymes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 34 | pages = 26066–73 | date = August 2000 | pmid = 10862613 | doi = 10.1074/jbc.M001831200 }}</ref> and
* [[UBE2I]],<ref name=pmid10961991/><ref name=pmid12924945/><ref name=pmid17353931>{{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}</ref><ref name=pmid8921390>{{cite journal | vauthors = Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ | title = Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system | journal = Genomics | volume = 37 | issue = 2 | pages = 183–6 | date = October 1996 | pmid = 8921390 | doi = 10.1006/geno.1996.0540 }}</ref>
{{Div col end}}
 
== 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 <ref name="Schwartz_2012">{{cite journal | vauthors = Schwartz RJ, Yeh ET | title = Weighing in on heart failure: the role of SERCA2a SUMOylation | journal = Circulation Research | volume = 110 | issue = 2 | pages = 198–9 | year = 2012 | pmid = 22267837 | doi = 10.1161/RES.0b013e318246f187 }}</ref>
 
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.<ref name="Periasamy_2001">{{cite journal | vauthors = Periasamy M, Huke S | title = SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac contractility | journal = Journal of Molecular and Cellular Cardiology | volume = 33 | issue = 6 | pages = 1053–63 | year = 2001 | pmid = 11444913 | doi = 10.1006/jmcc.2001.1366 }}</ref> 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.<ref name="Kho_2011">{{cite journal | vauthors = Kho C, Lee A, Jeong D, Oh JG, Chaanine AH, Kizana E, Park WJ, Hajjar RJ | title = SUMO1-dependent modulation of SERCA2a in heart failure | journal = Nature | volume = 477 | issue = 7366 | pages = 601–5 | year = 2011 | pmid = 21900893 | pmc = 3443490 | doi = 10.1038/nature10407 }}</ref>
 
== 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.<ref name="Kho_2011" />  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.<ref name="Kho_2011" />
 
== See also ==
* [[SENP6]]
 
== References ==
{{reflist}}
 
== Further reading ==
{{Refbegin |33em}}
* {{cite journal | vauthors = Cookson MR | title = Pathways to Parkinsonism | journal = Neuron | volume = 37 | issue = 1 | pages = 7–10 | date = January 2003 | pmid = 12526767 | doi = 10.1016/S0896-6273(02)01166-2 }}
* {{cite journal | vauthors = Boddy MN, Howe K, Etkin LD, Solomon E, Freemont PS | title = PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia | journal = Oncogene | volume = 13 | issue = 5 | pages = 971–82 | date = September 1996 | pmid = 8806687 | doi =  }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ | title = Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system | journal = Genomics | volume = 37 | issue = 2 | pages = 183–6 | date = October 1996 | pmid = 8921390 | doi = 10.1006/geno.1996.0540 }}
* {{cite journal | vauthors = Matunis MJ, Coutavas E, Blobel G | title = A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex | journal = The Journal of Cell Biology | volume = 135 | issue = 6 Pt 1 | pages = 1457–70 | date = December 1996 | pmid = 8978815 | pmc = 2133973 | doi = 10.1083/jcb.135.6.1457 }}
* {{cite journal | vauthors = Mahajan R, Delphin C, Guan T, Gerace L, Melchior F | title = A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2 | journal = Cell | volume = 88 | issue = 1 | pages = 97–107 | date = January 1997 | pmid = 9019411 | doi = 10.1016/S0092-8674(00)81862-0 }}
* {{cite journal | vauthors = Lapenta V, Chiurazzi P, van der Spek P, Pizzuti A, Hanaoka F, Brahe C | title = SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family | journal = Genomics | volume = 40 | issue = 2 | pages = 362–6 | date = March 1997 | pmid = 9119407 | doi = 10.1006/geno.1996.4556 }}
* {{cite journal | vauthors = Kamitani T, Nguyen HP, Yeh ET | title = Preferential modification of nuclear proteins by a novel ubiquitin-like molecule | journal = The Journal of Biological Chemistry | volume = 272 | issue = 22 | pages = 14001–4 | date = May 1997 | pmid = 9162015 | doi = 10.1074/jbc.272.22.14001 }}
* {{cite journal | vauthors = Mahajan R, Gerace L, Melchior F | title = Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association | journal = The Journal of Cell Biology | volume = 140 | issue = 2 | pages = 259–70 | date = January 1998 | pmid = 9442102 | pmc = 2132567 | doi = 10.1083/jcb.140.2.259 }}
* {{cite journal | vauthors = Howe K, Williamson J, Boddy N, Sheer D, Freemont P, Solomon E | title = The ubiquitin-homology gene PIC1: characterization of mouse (Pic1) and human (UBL1) genes and pseudogenes | journal = Genomics | volume = 47 | issue = 1 | pages = 92–100 | date = January 1998 | pmid = 9465300 | doi = 10.1006/geno.1997.5091 }}
* {{cite journal | vauthors = Bayer P, Arndt A, Metzger S, Mahajan R, Melchior F, Jaenicke R, Becker J | title = Structure determination of the small ubiquitin-related modifier SUMO-1 | journal = Journal of Molecular Biology | volume = 280 | issue = 2 | pages = 275–86 | date = July 1998 | pmid = 9654451 | doi = 10.1006/jmbi.1998.1839 }}
* {{cite journal | vauthors = Desterro JM, Rodriguez MS, Hay RT | title = SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation | journal = Molecular Cell | volume = 2 | issue = 2 | pages = 233–9 | date = August 1998 | pmid = 9734360 | doi = 10.1016/S1097-2765(00)80133-1 }}
* {{cite journal | vauthors = Juo P, Kuo CJ, Yuan J, Blenis J | title = Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade | journal = Current Biology | volume = 8 | issue = 18 | pages = 1001–8 | date = September 1998 | pmid = 9740801 | doi = 10.1016/S0960-9822(07)00420-4 }}
* {{cite journal | vauthors = Kamitani T, Kito K, Nguyen HP, Wada H, Fukuda-Kamitani T, Yeh ET | title = Identification of three major sentrinization sites in PML | journal = The Journal of Biological Chemistry | volume = 273 | issue = 41 | pages = 26675–82 | date = October 1998 | pmid = 9756909 | doi = 10.1074/jbc.273.41.26675 }}
* {{cite journal | vauthors = Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN, Solomon E, de Thé H, Hay RT, Freemont PS | title = SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation | journal = Journal of Cell Science | volume = 112 ( Pt 3) | issue = 3 | pages = 381–93 | date = February 1999 | pmid = 9885291 | doi =  }}
* {{cite journal | vauthors = Chen A, Mannen H, Li SS | title = Characterization of mouse ubiquitin-like SMT3A and SMT3B cDNAs and gene/pseudogenes | journal = Biochemistry and Molecular Biology International | volume = 46 | issue = 6 | pages = 1161–74 | date = December 1998 | pmid = 9891849 | doi = 10.1080/15216549800204722 }}
* {{cite journal | vauthors = Okuma T, Honda R, Ichikawa G, Tsumagari N, Yasuda H | title = In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2 | journal = Biochemical and Biophysical Research Communications | volume = 254 | issue = 3 | pages = 693–8 | date = January 1999 | pmid = 9920803 | doi = 10.1006/bbrc.1998.9995 }}
* {{cite journal | vauthors = Liou ML, Liou HC | title = The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 10145–53 | date = April 1999 | pmid = 10187798 | doi = 10.1074/jbc.274.15.10145 }}
{{Refend}}
 
== External links ==
* {{UCSC genome browser|SUMO1}}
* {{UCSC gene details|SUMO1}}
{{PDB Gallery|geneid=7341}}

Revision as of 00:04, 12 September 2017

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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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 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]

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. This particular heart protein may be an exciting and novel target for heart failure treatment in the future.[25]

See also

References

  1. ↑ Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (September 1996). "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. ↑ 2.0 2.1 2.2 Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ET (November 1996). "Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin". Journal of Immunology. 157 (10): 4277–81. PMID 8906799.
  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 in Genetics. 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. ↑ "Molecular Interaction Database".
  7. ↑ 7.0 7.1 Lin DY, Shih HM (July 2002). "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. doi:10.1074/jbc.M200633200. PMID 11948183.
  8. ↑ 8.0 8.1 Ryu SW, Chae SK, Kim E (December 2000). "Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9". Biochemical and Biophysical Research Communications. 279 (1): 6–10. doi:10.1006/bbrc.2000.3882. PMID 11112409.
  9. ↑ 9.0 9.1 Ivanchuk SM, Mondal S, Rutka JT (June 2008). "p14ARF interacts with DAXX: effects on HDM2 and p53". Cell Cycle. 7 (12): 1836–50. doi:10.4161/cc.7.12.6025. PMID 18583933.
  10. ↑ Kang ES, Park CW, Chung JH (December 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". Biochemical and Biophysical Research Communications. 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. PMID 11735126.
  11. ↑ 11.0 11.1 11.2 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". The Journal of Biological Chemistry. 275 (46): 36316–23. doi:10.1074/jbc.M004293200. PMID 10961991.
  12. ↑ Lee BH, Yoshimatsu K, Maeda A, Ochiai K, Morimatsu M, Araki K, Ogino M, Morikawa S, Arikawa J (December 2003). "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. doi:10.1016/j.virusres.2003.09.001. PMID 14609633.
  13. ↑ Kahyo T, Nishida T, Yasuda H (September 2001). "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Molecular Cell. 8 (3): 713–8. doi:10.1016/S1097-2765(01)00349-5. PMID 11583632.
  14. ↑ Kamitani T, Nguyen HP, Kito K, Fukuda-Kamitani T, Yeh ET (February 1998). "Covalent modification of PML by the sentrin family of ubiquitin-like proteins". The Journal of Biological Chemistry. 273 (6): 3117–20. doi:10.1074/jbc.273.6.3117. PMID 9452416.
  15. ↑ 15.0 15.1 Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y (August 2003). "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry. 42 (33): 9959–69. doi:10.1021/bi0345283. PMID 12924945.
  16. ↑ Gong L, Li B, Millas S, Yeh ET (April 1999). "Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex". FEBS Letters. 448 (1): 185–9. doi:10.1016/S0014-5793(99)00367-1. PMID 10217437.
  17. ↑ Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC, Hung JJ (July 2008). "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. doi:10.1016/j.jmb.2008.05.043. PMID 18572193.
  18. ↑ Hardeland U, Steinacher R, Jiricny J, Schär P (March 2002). "Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover". The EMBO Journal. 21 (6): 1456–64. doi:10.1093/emboj/21.6.1456. PMC 125358. PMID 11889051.
  19. ↑ 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. doi:10.1074/jbc.274.15.10145. PMID 10187798.
  20. ↑ 20.0 20.1 Mao Y, Desai SD, Liu LF (August 2000). "SUMO-1 conjugation to human DNA topoisomerase II isozymes". The Journal of Biological Chemistry. 275 (34): 26066–73. doi:10.1074/jbc.M001831200. PMID 10862613.
  21. ↑ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  22. ↑ 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. doi:10.1006/geno.1996.0540. PMID 8921390.
  23. ↑ Schwartz RJ, Yeh ET (2012). "Weighing in on heart failure: the role of SERCA2a SUMOylation". Circulation Research. 110 (2): 198–9. doi:10.1161/RES.0b013e318246f187. PMID 22267837.
  24. ↑ Periasamy M, Huke S (2001). "SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac contractility". Journal of Molecular and Cellular Cardiology. 33 (6): 1053–63. doi:10.1006/jmcc.2001.1366. PMID 11444913.
  25. ↑ 25.0 25.1 25.2 Kho C, Lee A, Jeong D, Oh JG, Chaanine AH, Kizana E, Park WJ, Hajjar RJ (2011). "SUMO1-dependent modulation of SERCA2a in heart failure". Nature. 477 (7366): 601–5. doi:10.1038/nature10407. PMC 3443490. PMID 21900893.

Further reading

External links

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