UBQLN1
Ubiquilin-1 is a protein that in humans is encoded by the UBQLN1 gene.[1][2][3]
Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and thus are thought to functionally link the ubiquitination machinery to the proteasome to effect in vivo protein degradation.
Possible Role In Preventing Alzheimers Disease
Ubiquilin has also been shown to modulate accumulation of presenilin proteins, and is found in lesions associated with Alzheimer's and Parkinson's disease. Two transcript variants encoding different isoforms have been found for this gene.[3]
Higher levels of ubiquilin-1 in the brain decreased malformation of the APP molecule which plays a key role in triggering Alzheimers disease.[4] Conversly, lower levels of ubiquilin-1 in the brain were associated with increased malformation of APP.[4]
Similarity to Non-human Proteins
Human ubiquitin (ubiquilin) shares high degree of similarity with related proteins in yeast, rat and frog.
Interactions
UBQLN1 has been shown to interact with
References
- ^ Ozaki T, Hishiki T, Toyama Y, Yuasa S, Nakagawara A, Sakiyama S (Oct 1997). "Identification of a new cellular protein that can interact specifically with DAN". DNA Cell Biol 16 (8): 985–91. doi:10.1089/dna.1997.16.985. PMID 9303440.
- ^ Hanaoka E, Ozaki T, Ohira M, Nakamura Y, Suzuki M, Takahashi E, Moriya H, Nakagawara A, Sakiyama S (Jul 2000). "Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3". J Hum Genet 45 (3): 188–91. doi:10.1007/s100380050209. PMID 10807547.
- ^ a b "Entrez Gene: UBQLN1 ubiquilin 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29979.
- ^ a b Stieren ES, El Ayadi A, Xiao Y, Siller E, Landsverk ML, Oberhauser AF, Barral JM, Boehning D (August 2011). "Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein". J Biol Chem. doi:10.1074/jbc.M111.243147. PMC 3195644. PMID 21852239. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3195644. Lay summary – Science Daily.
- ^ Kim TY, Kim E, Yoon SK, Yoon JB (May 2008). "Herp enhances ER-associated protein degradation by recruiting ubiquilins". Biochem. Biophys. Res. Commun. 369 (2): 741–6. doi:10.1016/j.bbrc.2008.02.086. PMID 18307982.
- ^ Wu S, Mikhailov A, Kallo-Hosein H, Hara K, Yonezawa K, Avruch J (January 2002). "Characterization of ubiquilin 1, an mTOR-interacting protein". Biochim. Biophys. Acta 1542 (1-3): 41–56. doi:10.1016/S0167-4889(01)00164-1. PMID 11853878.
- ^ Ko HS, Uehara T, Nomura Y (September 2002). "Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death". J. Biol. Chem. 277 (38): 35386–92. doi:10.1074/jbc.M203412200. PMID 12095988.
- ^ a b Mah AL, Perry G, Smith MA, Monteiro MJ (November 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. 151 (4): 847–62. doi:10.1083/jcb.151.4.847. PMC 2169435. PMID 11076969. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2169435.
- ^ Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (August 2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome". Mol. Cell 6 (2): 409–19. doi:10.1016/S1097-2765(00)00040-X. PMID 10983987.
Further reading
- Ozaki T, Kondo K, Nakamura Y, et al. (1997). "Interaction of DA41, a DAN-binding protein, with the epidermal growth factor-like protein, S(1-5).". Biochem. Biophys. Res. Commun. 237 (2): 245–50. doi:10.1006/bbrc.1997.7122. PMID 9268694.
- Ozaki T, Hanaoka E, Naka M, et al. (1999). "Cloning and characterization of rat BAT3 cDNA.". DNA Cell Biol. 18 (6): 503–12. doi:10.1089/104454999315222. PMID 10390159.
- Wu AL, Wang J, Zheleznyak A, Brown EJ (1999). "Ubiquitin-related proteins regulate interaction of vimentin intermediate filaments with the plasma membrane.". Mol. Cell 4 (4): 619–25. doi:10.1016/S1097-2765(00)80212-9. PMID 10549293.
- Kleijnen MF, Shih AH, Zhou P, et al. (2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome.". Mol. Cell 6 (2): 409–19. doi:10.1016/S1097-2765(00)00040-X. PMID 10983987.
- Mah AL, Perry G, Smith MA, Monteiro MJ (2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation.". J. Cell Biol. 151 (4): 847–62. doi:10.1083/jcb.151.4.847. PMC 2169435. PMID 11076969. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2169435.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311072.
- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1083732.
- Bedford FK, Kittler JT, Muller E, et al. (2001). "GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1.". Nat. Neurosci. 4 (9): 908–16. doi:10.1038/nn0901-908. PMID 11528422.
- Wu S, Mikhailov A, Kallo-Hosein H, et al. (2002). "Characterization of ubiquilin 1, an mTOR-interacting protein.". Biochim. Biophys. Acta 1542 (1-3): 41–56. doi:10.1016/S0167-4889(01)00164-1. PMID 11853878.
- Ko HS, Uehara T, Nomura Y (2002). "Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death.". J. Biol. Chem. 277 (38): 35386–92. doi:10.1074/jbc.M203412200. PMID 12095988.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Gao L, Tu H, Shi ST, et al. (2003). "Interaction with a ubiquitin-like protein enhances the ubiquitination and degradation of hepatitis C virus RNA-dependent RNA polymerase.". J. Virol. 77 (7): 4149–59. doi:10.1128/JVI.77.7.4149-4159.2003. PMC 150629. PMID 12634373. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=150629.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Massey LK, Mah AL, Ford DL, et al. (2004). "Overexpression of ubiquilin decreases ubiquitination and degradation of presenilin proteins.". J. Alzheimers Dis. 6 (1): 79–92. PMID 15004330.
- Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442148.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Persson P, Stockhausen MT, Påhlman S, Axelson H (2005). "Ubiquilin-1 is a novel HASH-1-complexing protein that regulates levels of neuronal bHLH transcription factors in human neuroblastoma cells.". Int. J. Oncol. 25 (5): 1213–21. PMID 15492808.
- Bertram L, Hiltunen M, Parkinson M, et al. (2005). "Family-based association between Alzheimer's disease and variants in UBQLN1.". N. Engl. J. Med. 352 (9): 884–94. doi:10.1056/NEJMoa042765. PMID 15745979.