View source for UBQLN1

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Ubiquilin-1''' is a [[protein]] that in humans is encoded by the ''UBQLN1'' [[gene]].<ref name="pmid9303440">{{cite journal | vauthors = Ozaki T, Hishiki T, Toyama Y, Yuasa S, Nakagawara A, Sakiyama S | title = Identification of a new cellular protein that can interact specifically with DAN | journal = DNA and Cell Biology | volume = 16 | issue = 8 | pages = 985–91 | date = August 1997 | pmid = 9303440 | doi = 10.1089/dna.1997.16.985 }}</ref><ref name="pmid10807547">{{cite journal | vauthors = Hanaoka E, Ozaki T, Ohira M, Nakamura Y, Suzuki M, Takahashi E, Moriya H, Nakagawara A, Sakiyama S | display-authors = 6 | title = Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3 | journal = Journal of Human Genetics | volume = 45 | issue = 3 | pages = 188–91 | date = Jul 2000 | pmid = 10807547 | doi = 10.1007/s100380050209 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: UBQLN1 ubiquilin 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29979}}</ref>
Ubiquilins contain two [[protein domain|domains]], an [[N-terminus|N-terminal]] [[ubiquitin-like protein|ubiquitin-like domain]] and a [[C-terminus|C-terminal]] [[ubiquitin-associated domain]]. They physically associate with both [[proteasome]]s and [[ubiquitin ligase]]s, and thus are thought to functionally link the [[ubiquitination]] machinery to the proteasome to effect ''in vivo'' [[protein degradation]].
==Functions==
Ubiquilin-1 is associated with [[protein degradation]] and aggregation of [[protein misfolding|misfolded protein]]s, and may be involved in [[neurodegenerative disease]]s.<ref name="haapasalo_2010">{{cite journal | vauthors = Haapasalo A, Viswanathan J, Bertram L, Soininen H, Tanzi RE, Hiltunen M | title = Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation | journal = Biochemical Society Transactions | volume = 38 | issue = Pt 1 | pages = 150–5 | date = February 2010 | pmid = 20074050 | doi = 10.1042/BST0380150 | hdl = 11858/00-001M-0000-0010-7C06-4 | hdl-access = free }}</ref><ref name="zhang_2009">{{cite journal | vauthors = Zhang C, Saunders AJ | title = An emerging role for Ubiquilin 1 in regulating protein quality control system and in disease pathogenesis | journal = Discovery Medicine | volume = 8 | issue = 40 | pages = 18–22 | date = June 2009 | pmid = 19772837 | pmc = 3158983 }}</ref> Ubiquilin-1 has been reported to act as a [[molecular chaperone]] for [[amyloid precursor protein]] (APP), a protein associated with [[Alzheimer's disease]].<ref name="pmid21852239">{{cite journal | vauthors = Stieren ES, El Ayadi A, Xiao Y, Siller E, Landsverk ML, Oberhauser AF, Barral JM, Boehning D | display-authors = 6 | title = Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein | journal = The Journal of Biological Chemistry | volume = 286 | issue = 41 | pages = 35689–98 | date = October 2011 | pmid = 21852239 | pmc = 3195644 | doi = 10.1074/jbc.M111.243147| doi-access = free }}
*{{cite press release |date=September 1, 2011 |title=Alzheimer's brains found to have lower levels of key protein |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2011/09/110901112537.htm}}</ref>
Ubiquilin-1 was first identified through its interactions with [[presenilin]]s.<ref name="mah_2000">{{cite journal | vauthors = Mah AL, Perry G, Smith MA, Monteiro MJ | title = Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation | journal = The Journal of Cell Biology | volume = 151 | issue = 4 | pages = 847–62 | date = November 2000 | pmid = 11076969 | doi = 10.1083/jcb.151.4.847 | pmc = 2169435 | doi-access = free }}</ref> Two transcript variants encoding different isoforms have been found for this gene.<ref name="entrez"/>
==Related proteins==
Human UBQLN1 shares a high degree of similarity with related ubiquilins including [[UBQLN2]] and [[UBQLN4]].<ref name="pmid24674348">{{cite journal | vauthors = Marín I | title = The ubiquilin gene family: evolutionary patterns and functional insights | journal = BMC Evolutionary Biology | volume = 14 | pages = 63 | date = March 2014 | issue = 1 | pmid = 24674348 | pmc = 4230246 | doi = 10.1186/1471-2148-14-63 | bibcode = 2014BMCEE..14...63M | doi-access = free }}</ref>
== Interactions ==
UBQLN1 has been shown to [[Protein-protein interaction|interact]] with
* [[HERPUD1]],<ref name="pmid18307982">{{cite journal | vauthors = Kim TY, Kim E, Yoon SK, Yoon JB | title = Herp enhances ER-associated protein degradation by recruiting ubiquilins | journal = Biochemical and Biophysical Research Communications | volume = 369 | issue = 2 | pages = 741–6 | date = May 2008 | pmid = 18307982 | doi = 10.1016/j.bbrc.2008.02.086 }}</ref>
* [[Mammalian target of rapamycin|MTOR]],<ref name="pmid11853878">{{cite journal | vauthors = Wu S, Mikhailov A, Kallo-Hosein H, Hara K, Yonezawa K, Avruch J | title = Characterization of ubiquilin 1, an mTOR-interacting protein | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1542 | issue = 1–3 | pages = 41–56 | date = January 2002 | pmid = 11853878 | doi = 10.1016/S0167-4889(01)00164-1 | doi-access = free }}</ref>
* [[P4HB]],<ref name="pmid12095988">{{cite journal | vauthors = Ko HS, Uehara T, Nomura Y | title = Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death | journal = The Journal of Biological Chemistry | volume = 277 | issue = 38 | pages = 35386–92 | date = September 2002 | pmid = 12095988 | doi = 10.1074/jbc.M203412200 | doi-access = free }}</ref>
* [[PSEN1]]<ref name="pmid11076969">{{cite journal | vauthors = Mah AL, Perry G, Smith MA, Monteiro MJ | title = Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation | journal = The Journal of Cell Biology | volume = 151 | issue = 4 | pages = 847–62 | date = November 2000 | pmid = 11076969 | pmc = 2169435 | doi = 10.1083/jcb.151.4.847 }}</ref>
* [[PSEN2]],<ref name=pmid11076969/> and
* [[UBE3A]].<ref name="pmid10983987">{{cite journal | vauthors = Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM | display-authors = 6 | title = The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome | journal = Molecular Cell | volume = 6 | issue = 2 | pages = 409–19 | date = August 2000 | pmid = 10983987 | doi = 10.1016/S1097-2765(00)00040-X | doi-access = free }}</ref>
* [[TMCO6]],<ref>{{cite journal | vauthors = Rolland T, Taşan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, Yi S, Lemmens I, Fontanillo C, Mosca R, Kamburov A, Ghiassian SD, Yang X, Ghamsari L, Balcha D, Begg BE, Braun P, Brehme M, Broly MP, Carvunis AR, Convery-Zupan D, Corominas R, Coulombe-Huntington J, Dann E, Dreze M, Dricot A, Fan C, Franzosa E, Gebreab F, Gutierrez BJ, Hardy MF, Jin M, Kang S, Kiros R, Lin GN, Luck K, MacWilliams A, Menche J, Murray RR, Palagi A, Poulin MM, Rambout X, Rasla J, Reichert P, Romero V, Ruyssinck E, Sahalie JM, Scholz A, Shah AA, Sharma A, Shen Y, Spirohn K, Tam S, Tejeda AO, Trigg SA, Twizere JC, Vega K, Walsh J, Cusick ME, Xia Y, Barabási AL, Iakoucheva LM, Aloy P, De Las Rivas J, Tavernier J, Calderwood MA, Hill DE, Hao T, Roth FP, Vidal M | display-authors = 6 | title = A proteome-scale map of the human interactome network | journal = Cell | volume = 159 | issue = 5 | pages = 1212–1226 | date = November 2014 | pmid = 25416956 | pmc = 4266588 | doi = 10.1016/j.cell.2014.10.050 }}</ref>
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Ozaki T, Kondo K, Nakamura Y, Ichimiya S, Nakagawara A, Sakiyama S | title = Interaction of DA41, a DAN-binding protein, with the epidermal growth factor-like protein, S(1-5) | journal = Biochemical and Biophysical Research Communications | volume = 237 | issue = 2 | pages = 245–50 | date = August 1997 | pmid = 9268694 | doi = 10.1006/bbrc.1997.7122 }}
* {{cite journal | vauthors = Ozaki T, Hanaoka E, Naka M, Nakagawara A, Sakiyama S | title = Cloning and characterization of rat BAT3 cDNA | journal = DNA and Cell Biology | volume = 18 | issue = 6 | pages = 503–12 | date = June 1999 | pmid = 10390159 | doi = 10.1089/104454999315222 }}
* {{cite journal | vauthors = Wu AL, Wang J, Zheleznyak A, Brown EJ | title = Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane | journal = Molecular Cell | volume = 4 | issue = 4 | pages = 619–25 | date = October 1999 | pmid = 10549293 | doi = 10.1016/S1097-2765(00)80212-9 | doi-access = free }}
* {{cite journal | vauthors = Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM | display-authors = 6 | title = The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome | journal = Molecular Cell | volume = 6 | issue = 2 | pages = 409–19 | date = August 2000 | pmid = 10983987 | doi = 10.1016/S1097-2765(00)00040-X | doi-access = free }}
* {{cite journal | vauthors = Mah AL, Perry G, Smith MA, Monteiro MJ | title = Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation | journal = The Journal of Cell Biology | volume = 151 | issue = 4 | pages = 847–62 | date = November 2000 | pmid = 11076969 | pmc = 2169435 | doi = 10.1083/jcb.151.4.847 }}
* {{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | display-authors = 6 | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}
* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
* {{cite journal | vauthors = Bedford FK, Kittler JT, Muller E, Thomas P, Uren JM, Merlo D, Wisden W, Triller A, Smart TG, Moss SJ | display-authors = 6 | title = GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1 | journal = Nature Neuroscience | volume = 4 | issue = 9 | pages = 908–16 | date = September 2001 | pmid = 11528422 | doi = 10.1038/nn0901-908 | s2cid = 13078743 }}
* {{cite journal | vauthors = Wu S, Mikhailov A, Kallo-Hosein H, Hara K, Yonezawa K, Avruch J | title = Characterization of ubiquilin 1, an mTOR-interacting protein | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1542 | issue = 1–3 | pages = 41–56 | date = January 2002 | pmid = 11853878 | doi = 10.1016/S0167-4889(01)00164-1 | doi-access = free }}
* {{cite journal | vauthors = Ko HS, Uehara T, Nomura Y | title = Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death | journal = The Journal of Biological Chemistry | volume = 277 | issue = 38 | pages = 35386–92 | date = September 2002 | pmid = 12095988 | doi = 10.1074/jbc.M203412200 | doi-access = free }}
* {{cite journal | vauthors = Gao L, Tu H, Shi ST, Lee KJ, Asanaka M, Hwang SB, Lai MM | title = Interaction with a ubiquitin-like protein enhances the ubiquitination and degradation of hepatitis C virus RNA-dependent RNA polymerase | journal = Journal of Virology | volume = 77 | issue = 7 | pages = 4149–59 | date = April 2003 | pmid = 12634373 | pmc = 150629 | doi = 10.1128/JVI.77.7.4149-4159.2003 }}
* {{cite journal | vauthors = Massey LK, Mah AL, Ford DL, Miller J, Liang J, Doong H, Monteiro MJ | title = Overexpression of ubiquilin decreases ubiquitination and degradation of presenilin proteins | journal = Journal of Alzheimer's Disease | volume = 6 | issue = 1 | pages = 79–92 | date = February 2004 | pmid = 15004330 | doi = 10.3233/jad-2004-6109 }}
* {{cite journal | vauthors = Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM | display-authors = 6 | title = Functional proteomics mapping of a human signaling pathway | journal = Genome Research | volume = 14 | issue = 7 | pages = 1324–32 | date = July 2004 | pmid = 15231748 | pmc = 442148 | doi = 10.1101/gr.2334104 }}
* {{cite journal | vauthors = Persson P, Stockhausen MT, Påhlman S, Axelson H | title = Ubiquilin-1 is a novel HASH-1-complexing protein that regulates levels of neuronal bHLH transcription factors in human neuroblastoma cells | journal = International Journal of Oncology | volume = 25 | issue = 5 | pages = 1213–21 | date = November 2004 | pmid = 15492808 | doi = 10.3892/ijo.25.5.1213 }}
* {{cite journal | vauthors = Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Velicelebi G, Moscarillo T, Hyman BT, Wagner SL, Becker KD, Blacker D, Tanzi RE | display-authors = 6 | title = Family-based association between Alzheimer's disease and variants in UBQLN1 | journal = The New England Journal of Medicine | volume = 352 | issue = 9 | pages = 884–94 | date = March 2005 | pmid = 15745979 | doi = 10.1056/NEJMoa042765 | doi-access = free }}
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