{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Small ubiquitin-related modifier 2''' is a protein that in humans is encoded by the ''SUMO2'' gene.<ref name="pmid8630065">{{cite journal | vauthors = Mannen H, Tseng HM, Cho CL, Li SS | title = Cloning and expression of human homolog HSMT3 to yeast SMT3 suppressor of MIF2 mutations in a centromere protein gene | journal = Biochemical and Biophysical Research Communications | volume = 222 | issue = 1 | pages = 178–80 | date = May 1996 | pmid = 8630065 | doi = 10.1006/bbrc.1996.0717 | url = https://zenodo.org/record/1229472 }}</ref>
== 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, SUMO2 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 two amino acids of the carboxy-terminus have been cleaved off. Numerous 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: SUMO2 SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6613}}</ref>
== Interactions ==
SUMO2 has been shown to interact with TRIM63<ref name=pmid11283016>{{cite journal | vauthors = Dai KS, Liew CC | title = A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain | journal = The Journal of Biological Chemistry | volume = 276 | issue = 26 | pages = 23992–9 | date = Jun 2001 | pmid = 11283016 | doi = 10.1074/jbc.M011208200 | doi-access = free }}</ref> and CFAP298.<ref name="pmid19471022">{{cite journal | vauthors = Golebiowski F, Matic I, Tatham MH, Cole C, Yin Y, Nakamura A, Cox J, Barton GJ, Mann M, Hay RT | title = System-wide changes to SUMO modifications in response to heat shock | journal = Science Signaling | volume = 2 | issue = 72 | pages = ra24 | year = 2009 | pmid = 19471022 | doi = 10.1126/scisignal.2000282 | s2cid = 33450256 }}</ref>
== Clinical significance ==
Deep hypothermia protects the brain from ischemic injury, which is why it's employed for major cardiovascular procedures that necessitate cardiopulmonary bypass and a period of circulatory arrest. With an experiment <ref name=":0">{{Cite journal |last1=Wang |first1=Liangli |last2=Ma |first2=Qing |last3=Yang |first3=Wei |last4=Mackensen |first4=G. Burkhard |last5=Paschen |first5=Wulf |date=November 2012 |title=Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons |journal=Journal of Neurochemistry |language=en |volume=123 |issue=3 |pages=349–359 |doi=10.1111/j.1471-4159.2012.07916.x |pmc=3466336 |pmid=22891650}}</ref> conducted to moderate hypothermia, small ubiquitin-like modifier (SUMO1-3) conjugation was significantly activated in the brain. The effects of hypothermia on SUMO conjugation were evaluated in this experiment<ref name=":0" /> using Western blot and immunohistochemistry in animals that were either normothermic (37 °C) or deep to moderate (18 °C, 24 °C, 30 °C) hypothermic cardiopulmonary bypass. In these cells, even 30 °C hypothermia was enough to significantly boost SUMO2/3-conjugated protein levels and nucleus accumulation. Deep hypothermia caused the SUMO-conjugating enzyme Ubc9 to translocate to the nucleus, implying that the increase in nuclear levels of SUMO2/3-conjugated proteins seen in hypothermic animals' brains is an active process. Deep hypothermia caused only a small increase in the amounts of SUMO2/3-conjugated proteins in primary neuronal cells. This shows that neurons in vivo have a greater capacity to activate this endogenous possibly neuroprotective mechanism when exposed to hypothermia than neurons in vitro. Identifying proteins that are SUMO2/3 conjugated during hypothermia could aid in the development of new preventive and therapeutic therapies to make neurons more resistant to a transient blood supply interruption.
== References == {{Reflist}} {{Clear}}
== Further reading == {{Refbegin|33em}} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{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 = Mar 1997 | pmid = 9119407 | doi = 10.1006/geno.1996.4556 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{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 = Feb 1998 | pmid = 9452416 | doi = 10.1074/jbc.273.6.3117 | doi-access = free }} * {{cite journal | vauthors = Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET | title = Characterization of a second member of the sentrin family of ubiquitin-like proteins | journal = The Journal of Biological Chemistry | volume = 273 | issue = 18 | pages = 11349–53 | date = May 1998 | pmid = 9556629 | doi = 10.1074/jbc.273.18.11349 | doi-access = free }} * {{cite journal | vauthors = Saitoh H, Hinchey J | title = Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 9 | pages = 6252–8 | date = Mar 2000 | pmid = 10692421 | doi = 10.1074/jbc.275.9.6252 | doi-access = free }} * {{cite journal | vauthors = Nishida T, Tanaka H, Yasuda H | title = A novel mammalian Smt3-specific isopeptidase 1 (SMT3IP1) localized in the nucleolus at interphase | journal = European Journal of Biochemistry | volume = 267 | issue = 21 | pages = 6423–7 | date = Nov 2000 | pmid = 11029585 | doi = 10.1046/j.1432-1327.2000.01729.x | doi-access = free }} * {{cite journal | vauthors = Dai KS, Liew CC | title = A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain | journal = The Journal of Biological Chemistry | volume = 276 | issue = 26 | pages = 23992–9 | date = Jun 2001 | pmid = 11283016 | doi = 10.1074/jbc.M011208200 | doi-access = free }} * {{cite journal | vauthors = Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT | title = Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35368–74 | date = Sep 2001 | pmid = 11451954 | doi = 10.1074/jbc.M104214200 | doi-access = free }} * {{cite journal | vauthors = Nishida T, Kaneko F, Kitagawa M, Yasuda H | title = Characterization of a novel mammalian SUMO-1/Smt3-specific isopeptidase, a homologue of rat axam, which is an axin-binding protein promoting beta-catenin degradation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 42 | pages = 39060–6 | date = Oct 2001 | pmid = 11489887 | doi = 10.1074/jbc.M103955200 | doi-access = free }} * {{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 = Mar 2002 | pmid = 11889051 | pmc = 125358 | doi = 10.1093/emboj/21.6.1456 }} * {{cite journal | vauthors = Kim J, Cantwell CA, Johnson PF, Pfarr CM, Williams SC | title = Transcriptional activity of CCAAT/enhancer-binding proteins is controlled by a conserved inhibitory domain that is a target for sumoylation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 41 | pages = 38037–44 | date = Oct 2002 | pmid = 12161447 | doi = 10.1074/jbc.M207235200 | doi-access = free }} * {{cite journal | vauthors = Su HL, Li SS | title = Molecular features of human ubiquitin-like SUMO genes and their encoded proteins | journal = Gene | volume = 296 | issue = 1–2 | pages = 65–73 | date = Aug 2002 | pmid = 12383504 | doi = 10.1016/S0378-1119(02)00843-0 }} * {{cite journal | vauthors = Petrie K, Guidez F, Howell L, Healy L, Waxman S, Greaves M, Zelent A | title = The histone deacetylase 9 gene encodes multiple protein isoforms | journal = The Journal of Biological Chemistry | volume = 278 | issue = 18 | pages = 16059–72 | date = May 2003 | pmid = 12590135 | doi = 10.1074/jbc.M212935200 | doi-access = free }} * {{cite journal | vauthors = Hietakangas V, Ahlskog JK, Jakobsson AM, Hellesuo M, Sahlberg NM, Holmberg CI, Mikhailov A, Palvimo JJ, Pirkkala L, Sistonen L | title = Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1 | journal = Molecular and Cellular Biology | volume = 23 | issue = 8 | pages = 2953–68 | date = Apr 2003 | pmid = 12665592 | pmc = 152542 | doi = 10.1128/MCB.23.8.2953-2968.2003 }} * {{cite journal | vauthors = Eaton EM, Sealy L | title = Modification of CCAAT/enhancer-binding protein-beta by the small ubiquitin-like modifier (SUMO) family members, SUMO-2 and SUMO-3 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 35 | pages = 33416–21 | date = Aug 2003 | pmid = 12810706 | doi = 10.1074/jbc.M305680200 | doi-access = free }} * {{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 = Aug 2003 | pmid = 12924945 | doi = 10.1021/bi0345283 }} * {{cite journal | vauthors = Chung TL, Hsiao HH, Yeh YY, Shia HL, Chen YL, Liang PH, Wang AH, Khoo KH, Shoei-Lung Li S | title = In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides | journal = The Journal of Biological Chemistry | volume = 279 | issue = 38 | pages = 39653–62 | date = Sep 2004 | pmid = 15272016 | doi = 10.1074/jbc.M405637200 | doi-access = free }} {{Refend}}
{{PDB Gallery|geneid=6613}}