{{short description|Protein in animal cells}} {{Infobox protein family | Symbol = SMN | Name = Survival motor neuron protein | image = Protein_SMN1_PDB_1g5v.png | width = | caption = Tudor domain from human SMN. PDB {{PDBe|1g5v}}<ref>{{cite journal | vauthors = Selenko P, Sprangers R, Stier G, Bühler D, Fischer U, Sattler M | title = SMN tudor domain structure and its interaction with the Sm proteins | journal = Nature Structural Biology | volume = 8 | issue = 1 | pages = 27–31 | date = January 2001 | pmid = 11135666 | doi = 10.1038/83014 }}</ref> | Pfam = PF06003 | Pfam_clan = CL0049 | InterPro = IPR010304 | SMART = | PROSITE = | MEROPS = | SCOP = 1mhn | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Survival of motor neuron''' or '''survival motor neuron''' ('''SMN''') is a [[protein]] that in humans is encoded by the ''[[SMN1]]'' and ''[[SMN2]]'' [[gene]]s.
SMN is found in the cytoplasm of all animal cells and also in the [[cell nucleus|nuclear]] [[cell nucleus#Cajal bodies and gems|gems]]. It functions in [[transcriptional regulation]], [[telomerase]] regeneration and [[active transport|cellular trafficking]].<ref>{{cite journal | vauthors = Singh NN, Shishimorova M, Cao LC, Gangwani L, Singh RN | title = A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy | journal = RNA Biology | volume = 6 | issue = 3 | pages = 341–50 | year = 2009 | pmid = 19430205 | pmc = 2734876 | doi=10.4161/rna.6.3.8723}}</ref> SMN deficiency, primarily due to [[mutation]]s in ''SMN1'', results in widespread [[RNA splicing|splicing]] defects, especially in spinal [[motor neuron]]s, and is one cause of [[spinal muscular atrophy]]. Research also showed a possible role of SMN in [[neuronal migration]] and/or [[cellular differentiation|differentiation]].<ref>{{cite journal | vauthors = Giavazzi A, Setola V, Simonati A, Battaglia G | title = Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system | journal = Journal of Neuropathology and Experimental Neurology | volume = 65 | issue = 3 | pages = 267–77 | date = March 2006 | pmid = 16651888 | doi = 10.1097/01.jnen.0000205144.54457.a3 | doi-access = free }}</ref>
== Function == The SMN protein contains [[GEMIN2 (gene)|GEMIN2]]-binding, [[Tudor domain|Tudor]] and YG-Box domains.<ref name=pmcid3519385>{{cite journal | vauthors = Martin R, Gupta K, Ninan NS, Perry K, Van Duyne GD | title = The survival motor neuron protein forms soluble glycine zipper oligomers | journal = Structure | volume = 20 | issue = 11 | pages = 1929–39 | date = November 2012 | pmid = 23022347 | pmc = 3519385 | doi = 10.1016/j.str.2012.08.024 }}</ref> It localizes to both the [[cytoplasm]] and the [[Cell nucleus|nucleus]]. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small [[ribonucleoprotein]]s (snRNPs). This protein forms heteromeric complexes with proteins such as GEMIN2 and [[GEMIN4]], and also interacts with several proteins known to be involved in the [[biogenesis]] of [[snRNP]]s, such as hnRNP U protein and the small nucleolar RNA binding protein.<ref name="entrez">{{cite web | title = Entrez Gene: SMN1 survival of motor neuron 1, telomeric| url = https://www.ncbi.nlm.nih.gov/gene/6606}}</ref>
== SMN complex == ''SMN complex'' refers to the entire multi-protein complex involved in the assembly of [[snRNP]]s, the essential components of [[spliceosome|spliceosomal machinery]].<ref name="Gubitz">{{cite journal | vauthors = Gubitz AK, Feng W, Dreyfuss G | title = The SMN complex | journal = Experimental Cell Research | volume = 296 | issue = 1 | pages = 51–6 | date = May 2004 | pmid = 15120993 | doi = 10.1016/j.yexcr.2004.03.022 }}</ref> The complex, apart from the "proper" survival of motor neuron protein, includes at least six other proteins ([[gem-associated protein 2]], [[DDX20|3]], [[gem-associated protein 4|4]], [[gem-associated protein 5|5]], [[gem-associated protein 6|6]] and [[gem-associated protein 7|7]].<ref name =Gubitz />
== Interactions ==
SMN has been shown to [[Protein-protein interaction|interact]] with: {{div col|colwidth=20em}} * [[Bcl-2]],<ref name=pmid9389483>{{cite journal | vauthors = Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y | title = Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy | journal = Nature | volume = 390 | issue = 6658 | pages = 413–7 | date = November 1997 | pmid = 9389483 | doi = 10.1038/37144 | bibcode = 1997Natur.390..413I }}</ref> * [[Coilin]],<ref name=pmid12361597>{{cite journal | vauthors = Hebert MD, Shpargel KB, Ospina JK, Tucker KE, Matera AG | title = Coilin methylation regulates nuclear body formation | journal = Developmental Cell | volume = 3 | issue = 3 | pages = 329–37 | date = September 2002 | pmid = 12361597 | doi = 10.1016/S1534-5807(02)00222-8 | doi-access = free }}</ref><ref name=pmid11641277>{{cite journal | vauthors = Hebert MD, Szymczyk PW, Shpargel KB, Matera AG | title = Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein | journal = Genes & Development | volume = 15 | issue = 20 | pages = 2720–9 | date = October 2001 | pmid = 11641277 | pmc = 312817 | doi = 10.1101/gad.908401 }}</ref> * [[DDX20]],<ref name=pmid10942426/><ref name=pmid11914277>{{cite journal | vauthors = Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, [[Juri Rappsilber|Rappsilber J]], Mann M, Dreyfuss G | title = miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs | journal = Genes & Development | volume = 16 | issue = 6 | pages = 720–8 | date = March 2002 | pmid = 11914277 | pmc = 155365 | doi = 10.1101/gad.974702 }}</ref><ref name=pmid10601333>{{cite journal | vauthors = Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G | title = Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems | journal = The Journal of Cell Biology | volume = 147 | issue = 6 | pages = 1181–94 | date = December 1999 | pmid = 10601333 | pmc = 2168095 | doi = 10.1083/jcb.147.6.1181 }}</ref> * [[DHX9]],<ref name=pmid11149922>{{cite journal | vauthors = Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G | title = A functional interaction between the survival motor neuron complex and RNA polymerase II | journal = The Journal of Cell Biology | volume = 152 | issue = 1 | pages = 75–85 | date = January 2001 | pmid = 11149922 | pmc = 2193649 | doi = 10.1083/jcb.152.1.75 }}</ref> * [[Fibrillarin|FBL]],<ref name=pmid11509230>{{cite journal | vauthors = Pellizzoni L, Baccon J, Charroux B, Dreyfuss G | title = The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1 | journal = Current Biology | volume = 11 | issue = 14 | pages = 1079–88 | date = July 2001 | pmid = 11509230 | doi = 10.1016/S0960-9822(01)00316-5 | doi-access = free | bibcode = 2001CBio...11.1079P }}</ref> * [[Far upstream element-binding protein 1|FUBP1]],<ref name=pmid10734235>{{cite journal | vauthors = Williams BY, Hamilton SL, Sarkar HK | title = The survival motor neuron protein interacts with the transactivator FUSE binding protein from human fetal brain | journal = FEBS Letters | volume = 470 | issue = 2 | pages = 207–10 | date = March 2000 | pmid = 10734235 | doi = 10.1016/S0014-5793(00)01320-X | bibcode = 2000FEBSL.470..207W }}</ref> * [[Nucleolar protein, member A1|GAR1]],<ref name=pmid11509230/> * [[Survival of motor neuron protein-interacting protein 1|GEMIN2]],<ref name=pmid10942426/><ref name=pmid9323129>{{cite journal | vauthors = Liu Q, Fischer U, Wang F, Dreyfuss G | title = The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins | journal = Cell | volume = 90 | issue = 6 | pages = 1013–21 | date = September 1997 | pmid = 9323129 | doi = 10.1016/S0092-8674(00)80367-0 | doi-access = free }}</ref> * [[GEMIN4]],<ref name=pmid10942426>{{cite journal | vauthors = Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U | title = Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins | journal = Human Molecular Genetics | volume = 9 | issue = 13 | pages = 1977–86 | date = August 2000 | pmid = 10942426 | doi = 10.1093/hmg/9.13.1977 | doi-access = free }}</ref> * [[GEMIN5]],<ref name=pmid11714716>{{cite journal | vauthors = Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G | title = Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins | journal = The Journal of Biological Chemistry | volume = 277 | issue = 7 | pages = 5631–6 | date = February 2002 | pmid = 11714716 | doi = 10.1074/jbc.M109448200 | doi-access = free }}</ref> * [[Gem-associated protein 7|GEMIN7]],<ref name=pmid12065586>{{cite journal | vauthors = Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G | title = Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 31957–62 | date = August 2002 | pmid = 12065586 | doi = 10.1074/jbc.M203478200 | doi-access = free }}</ref><ref name=pmid11748230>{{cite journal | vauthors = Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G | title = Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component | journal = The Journal of Biological Chemistry | volume = 277 | issue = 9 | pages = 7540–5 | date = March 2002 | pmid = 11748230 | doi = 10.1074/jbc.M110141200 | doi-access = free }}</ref> * [[HNRNPR]],<ref name=pmid11574476>{{cite journal | vauthors = Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G | title = SMN interacts with a novel family of hnRNP and spliceosomal proteins | journal = The EMBO Journal | volume = 20 | issue = 19 | pages = 5443–52 | date = October 2001 | pmid = 11574476 | pmc = 125643 | doi = 10.1093/emboj/20.19.5443 }}</ref><ref name=pmid11773003>{{cite journal | vauthors = Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M | title = Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? | journal = Human Molecular Genetics | volume = 11 | issue = 1 | pages = 93–105 | date = January 2002 | pmid = 11773003 | doi = 10.1093/hmg/11.1.93 | doi-access = free }}</ref> * [[KPNB1]],<ref name=pmid12095920>{{cite journal | vauthors = Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG | title = SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta | journal = Human Molecular Genetics | volume = 11 | issue = 15 | pages = 1785–95 | date = July 2002 | pmid = 12095920 | pmc = 1630493 | doi = 10.1093/hmg/11.15.1785 }}</ref> * [[P53]],<ref name=pmid11704667>{{cite journal | vauthors = Young PJ, Day PM, Zhou J, Androphy EJ, Morris GE, Lorson CL | title = A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy | journal = The Journal of Biological Chemistry | volume = 277 | issue = 4 | pages = 2852–9 | date = January 2002 | pmid = 11704667 | doi = 10.1074/jbc.M108769200 | doi-access = free }}</ref> * [[Small nuclear ribonucleoprotein D1|SNRPD1]],<ref name=pmid10942426/><ref name=pmid9323129/><ref name=pmid10851237>{{cite journal | vauthors = Friesen WJ, Dreyfuss G | title = Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN) | journal = The Journal of Biological Chemistry | volume = 275 | issue = 34 | pages = 26370–5 | date = August 2000 | pmid = 10851237 | doi = 10.1074/jbc.M003299200 | doi-access = free }}</ref> and * [[Small nuclear ribonucleoprotein D2|SNRPD2]].<ref name=pmid10942426/> {{Div col end}}
==Evolutionary conservation== SMN is evolutionarily conserved including the [[Fungi]] kingdom, though only fungal organisms with a great number of [[intron]]s have the ''Smn'' gene (or the [[splicing factor]] [[spf30]] [[paralogue]]). Surprisingly, these are filamentous fungus which have [[mycelia]], so suggesting [[Analogy (biology)|analogy]] to the neuronal axons.<ref>{{cite journal | vauthors = Mier P, Pérez-Pulido AJ | title = Fungal Smn and Spf30 homologues are mainly present in filamentous fungi and genomes with many introns: implications for spinal muscular atrophy | journal = Gene | volume = 491 | issue = 2 | pages = 135–41 | date = January 2012 | pmid = 22020225 | doi = 10.1016/j.gene.2011.10.006 | url = https://zenodo.org/record/897704 }}</ref>
== See also == * [[Gideon Dreyfuss]]
== References == {{Reflist}}
== External links == * {{MeshName|SMN+protein+(spinal+muscular+atrophy)}}
{{Chaperones}} {{Nucleus}}
[[Category:Motor system]] [[Category:Spinal muscular atrophy]]