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.
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] Conversely, lower levels of ubiquilin-1 in the brain were associated with increased malformation of APP.[4]
Similarity to Other Proteins
Human UBQLN1 shares a high degree of similarity with related ubiquilins including UBQLN2 and UBQLN4.[5]
↑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. PMID9303440.
↑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. PMID10807547.
↑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. PMID18307982.
↑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. PMID11853878.
↑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. PMID12095988.
↑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. PMID10983987.
↑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 RJ, Tavernier J, Calderwood MA, Hill DE, Hao T, Roth FP, Vidal M (2014). "A proteome-scale map of the human interactome network". Cell. 159: 1212–26. doi:10.1016/j.cell.2014.10.050. PMC4266588. PMID25416956.
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. PMID9268694.
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. PMID10390159.
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. PMID10549293.
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. PMID10983987.
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. PMID11528422.
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. PMID11853878.
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. PMID12095988.
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. PMID14702039.
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. PMID15004330.
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. doi:10.3892/ijo.25.5.1213. PMID15492808.
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. PMID15745979.