Gene Symbol: UBQLN2
Description: ubiquilin 2
Alias: ALS15, CHAP1, DSK2, HRIHFB2157, N4BP4, PLIC2, ubiquilin-2, Nedd4 binding protein 4, protein linking IAP with cytoskeleton 2, ubiquitin-like product Chap1/Dsk2
Species: human
Products:     UBQLN2

Top Publications

  1. Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff C, Ugolino J, et al. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Hum Mol Genet. 2010;19:3219-32 pubmed publisher
  2. Ford D, Monteiro M. Dimerization of ubiquilin is dependent upon the central region of the protein: evidence that the monomer, but not the dimer, is involved in binding presenilins. Biochem J. 2006;399:397-404 pubmed
    ..Our results provide new insight into the regulatory mechanism underlying the interaction of ubiquilin with presenilins. ..
  3. N Diaye E, Kajihara K, Hsieh I, Morisaki H, Debnath J, Brown E. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO Rep. 2009;10:173-9 pubmed publisher
    ..Depletion of UBQLN delays the delivery of autophagosomes to lysosomes. This study identifies a new role for UBQLN in regulating the maturation of autophagy, expanding the involvement of ubiquitin-related proteins in this process. ..
  4. Deng H, Chen W, Hong S, Boycott K, Gorrie G, Siddique N, et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature. 2011;477:211-5 pubmed publisher
    ..Here we show that mutations in UBQLN2, which encodes the ubiquitin-like protein ubiquilin?2, cause dominantly inherited, chromosome-X-linked ALS and ALS/..
  5. Brettschneider J, Van Deerlin V, Robinson J, Kwong L, Lee E, Ali Y, et al. Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion. Acta Neuropathol. 2012;123:825-39 pubmed publisher
    C9ORF72-hexanucleotide repeat expansions and ubiquilin-2 (UBQLN2) mutations are recently identified genetic markers in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)...
  6. Rutherford N, Lewis J, Clippinger A, Thomas M, Adamson J, Cruz P, et al. Unbiased screen reveals ubiquilin-1 and -2 highly associated with huntingtin inclusions. Brain Res. 2013;1524:62-73 pubmed publisher
    ..Thus, the co-localization of ubiquilin-2 with the huntingtin aggregates does not appear to facilitate aggregate removal. ..
  7. Gkazi S, Troakes C, Topp S, Miller J, Vance C, Sreedharan J, et al. Striking phenotypic variation in a family with the P506S UBQLN2 mutation including amyotrophic lateral sclerosis, spastic paraplegia, and frontotemporal dementia. Neurobiol Aging. 2019;73:229.e5-229.e9 pubmed publisher
    ..lateral sclerosis (ALS) and frontotemporal dementia identified 2 individuals who harbored a P497H and P506S UBQLN2 mutation, respectively (n = 0.9%)...
  8. Senturk M, Lin G, Zuo Z, Mao D, Watson E, Mikos A, et al. Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification. Nat Cell Biol. 2019;21:384-396 pubmed publisher
    ..Mutations in genes encoding ubiquilins, UBQLN2 and UBQLN4, cause familial ALS...
  9. Samant R, Livingston C, Sontag E, Frydman J. Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control. Nature. 2018;563:407-411 pubmed publisher
    ..ubiquitin codes for nuclear and cytoplasmic PQC appear to be linked to the function of the ubiquilin protein Dsk2, which is specifically required to clear nuclear misfolded proteins...

More Information

Publications103 found, 100 shown here

  1. Chen X, Ebelle D, Wright B, Sridharan V, Hooper E, Walters K. Structure of hRpn10 Bound to UBQLN2 UBL Illustrates Basis for Complementarity between Shuttle Factors and Substrates at the Proteasome. J Mol Biol. 2019;431:939-955 pubmed publisher
    ..Here, we define how hRpn10 binds to the UBQLN2 UBL domain, solving the structure of this complex by NMR, and determine affinities for each UIM region by a ..
  2. Chen T, Huang B, Shi X, Gao L, Huang C. Mutant UBQLN2P497H in motor neurons leads to ALS-like phenotypes and defective autophagy in rats. Acta Neuropathol Commun. 2018;6:122 pubmed publisher
    Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear...
  3. Alexander E, Ghanbari Niaki A, Zhang T, Sarkar J, Liu Y, Nirujogi R, et al. Ubiquilin 2 modulates ALS/FTD-linked FUS-RNA complex dynamics and stress granule formation. Proc Natl Acad Sci U S A. 2018;115:E11485-E11494 pubmed publisher
    The ubiquitin-like protein ubiquilin 2 (UBQLN2) has been genetically and pathologically linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but its normal cellular functions are ..
  4. Picher Martel V, Renaud L, Bareil C, Julien J. Neuronal Expression of UBQLN2P497H Exacerbates TDP-43 Pathology in TDP-43G348C Mice through Interaction with Ubiquitin. Mol Neurobiol. 2018;: pubmed publisher
    Mutations in the gene encoding ubiquilin-2 (UBQLN2) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)...
  5. Sharkey L, Safren N, Pithadia A, Gerson J, Dulchavsky M, Fischer S, et al. Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly. Proc Natl Acad Sci U S A. 2018;115:E10495-E10504 pubmed publisher
    b>UBQLN2 is one of a family of proteins implicated in ubiquitin-dependent protein quality control and integrally tied to human neurodegenerative disease...
  6. Ajroud Driss S, Siddique T. Sporadic and hereditary amyotrophic lateral sclerosis (ALS). Biochim Biophys Acta. 2015;1852:679-84 pubmed publisher
    ..and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways...
  7. Liu Z, Li H, Tan G, Tao Q, Ni W, Cheng X, et al. Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system. Neurobiol Aging. 2014;35:2881.e11-2881.e15 pubmed publisher
    ..to screen 18 causative genes of ALS, including SOD1, SETX, FUS, ANG, TARDBP, ALS2, FIG4, VAPB, OPTN, DAO, VCP, UBQLN2, SPG11, SIGMAR1, DCTN1, SQSTM1, PFN1, and CHMP2B in 8 ALS probands. Using this approach, we got an average of 9...
  8. Ceballos Diaz C, Rosario A, Park H, Chakrabarty P, Sacino A, Cruz P, et al. Viral expression of ALS-linked ubiquilin-2 mutants causes inclusion pathology and behavioral deficits in mice. Mol Neurodegener. 2015;10:25 pubmed publisher
    b>UBQLN2 mutations have recently been associated with familial forms of amyotrophic lateral sclerosis (ALS) and ALS-dementia...
  9. Kama R, Gabriely G, Kanneganti V, Gerst J. Cdc48 and ubiquilins confer selective anterograde protein sorting and entry into the multivesicular body in yeast. Mol Biol Cell. 2018;29:948-963 pubmed publisher
    ..We demonstrate that Cdc48 and the ubiquilin-like proteins in yeast also play a role in the anterograde trafficking of proteins, in this case the vacuolar protease, Cps1. ..
  10. Wu Q, Liu M, Huang C, Liu X, Huang B, Li N, et al. Pathogenic Ubqln2 gains toxic properties to induce neuron death. Acta Neuropathol. 2015;129:417-28 pubmed publisher
    Mutations in ubiquilin 2 (Ubqln2) is linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration...
  11. Jantrapirom S, Lo Piccolo L, Yoshida H, Yamaguchi M. Depletion of Ubiquilin induces an augmentation in soluble ubiquitinated Drosophila TDP-43 to drive neurotoxicity in the fly. Biochim Biophys Acta Mol Basis Dis. 2018;1864:3038-3049 pubmed publisher
    ..Missense mutations in UBQLN2 have been linked to X-linked dominant amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD)...
  12. Nowicka U, Zhang D, Walker O, Krutauz D, Castañeda C, Chaturvedi A, et al. DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin. Structure. 2015;23:542-57 pubmed publisher
    ..Unlike the other proteasomal shuttles, Rad23 and Dsk2, Ddi1 remains an enigma: its function is not fully understood and structural properties are poorly characterized...
  13. Lin K, Tsai P, Liao Y, Chen W, Tsai C, Soong B, et al. Mutational analysis of MATR3 in Taiwanese patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2015;36:2005.e1-4 pubmed publisher
    ..diagnoses of 169 patients remained elusive after mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, and HNRNPA2B1 had been excluded. We identified 1 heterozygous missense mutation, p...
  14. Volpe N, Simonett J, Fawzi A, Siddique T. Ophthalmic Manifestations of Amyotrophic Lateral Sclerosis (An American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. 2015;113:T12 pubmed
    ..studied histopathologically as well as the retinas of ALS/dementia transgenic mice with dysfunctional ubiquilin2, UBQLN2(P497H)...
  15. Teyssou E, Chartier L, Amador M, Lam R, Lautrette G, Nicol M, et al. Novel UBQLN2 mutations linked to amyotrophic lateral sclerosis and atypical hereditary spastic paraplegia phenotype through defective HSP70-mediated proteolysis. Neurobiol Aging. 2017;58:239.e11-239.e20 pubmed publisher
    Mutations in UBQLN2 have been associated with rare cases of X-linked juvenile and adult forms of amyotrophic lateral sclerosis (ALS) and ALS linked to frontotemporal dementia (FTD). Here, we report 1 known (c.1489C>T, p...
  16. Hochrainer K, Kroismayr R, Baranyi U, Binder B, Lipp J. Highly homologous HERC proteins localize to endosomes and exhibit specific interactions with hPLIC and Nm23B. Cell Mol Life Sci. 2008;65:2105-17 pubmed publisher
    ..In summary, although small HERC proteins are highly homologous showing the same subcellular distribution, they undergo different molecular interactions. ..
  17. Lin G, Mao D, Bellen H. Amyotrophic Lateral Sclerosis Pathogenesis Converges on Defects in Protein Homeostasis Associated with TDP-43 Mislocalization and Proteasome-Mediated Degradation Overload. Curr Top Dev Biol. 2017;121:111-171 pubmed publisher
    ..In this review, we focus on seven ALS-causing genes: TDP-43, FUS, C9orf72, VCP, UBQLN2, VAPB and SOD-1, which encompass about 90% of the variants causing familial ALS...
  18. ÖzoÄŸuz A, Uyan Ã, Birdal G, Iskender C, Kartal E, Lahut S, et al. The distinct genetic pattern of ALS in Turkey and novel mutations. Neurobiol Aging. 2015;36:1764.e9-1764.e18 pubmed publisher
    ..Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey...
  19. Synofzik M, Otto M, Ludolph A, Weishaupt J. [Genetic architecture of amyotrophic lateral sclerosis and frontotemporal dementia : Overlap and differences]. Nervenarzt. 2017;88:728-735 pubmed publisher
    ..g., C9orf72, TARDBP, GRN, TBK1, UBQLN2, VCP, CHCHD10, or SQSTM1...
  20. Subudhi I, Shorter J. Ubiquilin 2: Shuttling Clients Out of Phase?. Mol Cell. 2018;69:919-921 pubmed publisher
    b>Ubiquilin 2 (UBQLN2) is an amyotrophic lateral sclerosis-linked molecular chaperone with a prion-like domain that directly engages ubiquitin to triage clients for proteasomal degradation. Dao et al...
  21. Ferrari R, Forabosco P, Vandrovcova J, Botía J, Guelfi S, Warren J, et al. Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis. Mol Neurodegener. 2016;11:21 pubmed publisher
    ..in the frontal and temporal cortices for 12 genes (MAPT, GRN, CHMP2B, CTSC, HLA-DRA, TMEM106B, C9orf72, VCP, UBQLN2, OPTN, TARDBP and FUS) associated with FTD and we then carried out gene set enrichment and pathway analyses, and ..
  22. Kim S, Stiles S, Feichtmeier J, Ramesh N, Zhan L, Scalf M, et al. Mutation-dependent aggregation and toxicity in a Drosophila model for UBQLN2-associated ALS. Hum Mol Genet. 2017;: pubmed publisher
    ..Mutations in a proline-rich-repeat region (PRR) of UBQLN2 cause amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD); however, neither the normal functions of ..
  23. Christianson J, Olzmann J, Shaler T, Sowa M, Bennett E, Richter C, et al. Defining human ERAD networks through an integrative mapping strategy. Nat Cell Biol. 2011;14:93-105 pubmed publisher
    ..This analysis supports an adaptive organization for the mammalian ERAD machinery and reveals a number of metazoan-specific genes not previously linked to ERAD. ..
  24. Tsuchiya H, Ohtake F, Arai N, Kaiho A, Yasuda S, Tanaka K, et al. In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome. Mol Cell. 2017;66:488-502.e7 pubmed publisher
    ..Mutating Cdc48 results in decreased selectivity, and lacking Rad23/Dsk2 abolishes interactions between ubiquitylated substrates and the proteasome...
  25. Gavriilidis C, Laredj L, Solinhac R, Messaddeq N, Viaud J, Laporte J, et al. The MTM1-UBQLN2-HSP complex mediates degradation of misfolded intermediate filaments in skeletal muscle. Nat Cell Biol. 2018;20:198-210 pubmed publisher
    ..This relies on the MTM1-UBQLN2 complex to recognize and guide these misfolded proteins to the proteasome and occurs prior to aggregate formation...
  26. Gorrie G, Fecto F, Radzicki D, Weiss C, Shi Y, Dong H, et al. Dendritic spinopathy in transgenic mice expressing ALS/dementia-linked mutant UBQLN2. Proc Natl Acad Sci U S A. 2014;111:14524-9 pubmed publisher
    Mutations in the gene encoding ubiquilin2 (UBQLN2) cause amyotrophic lateral sclerosis (ALS), frontotemporal type of dementia, or both. However, the molecular mechanisms are unknown...
  27. Ferreira R, Menezes R, Rodrigues Pousada C. E4-Ubiquitin ligase Ufd2 stabilizes Yap8 and modulates arsenic stress responses independent of the U-box motif. Biol Open. 2015;4:1122-31 pubmed publisher
    ..Thus, our data disclose a novel Ufd2 role beyond degradation. This finding is further supported by genetic analyses showing that proteins belonging to Ufd2 proteolytic pathways, namely Ubc4, Rad23 and Dsk2, mediate Yap8 degradation.
  28. Blokhuis A, Koppers M, Groen E, Van den Heuvel D, Dini Modigliani S, Anink J, et al. Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways. Acta Neuropathol. 2016;132:175-96 pubmed publisher
    ..binding partners of wild-type (WT) and ALS-associated mutant versions of ATXN2, C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal cells. This analysis identified several known but also many novel binding partners of these proteins...
  29. Dao T, Kolaitis R, Kim H, O Donovan K, Martyniak B, Colicino E, et al. Ubiquitin Modulates Liquid-Liquid Phase Separation of UBQLN2 via Disruption of Multivalent Interactions. Mol Cell. 2018;69:965-978.e6 pubmed publisher
    ..Here we show that stress granules include proteasomal shuttle factor UBQLN2, an LCD-containing protein structurally and functionally distinct from RNA-binding proteins...
  30. Picher Martel V, Dutta K, Phaneuf D, Sobue G, Julien J. Ubiquilin-2 drives NF-κB activity and cytosolic TDP-43 aggregation in neuronal cells. Mol Brain. 2015;8:71 pubmed publisher
    Mutations in the gene encoding Ubiquilin-2 (UBQLN2) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)...
  31. Tsai P, Liu Y, Lin K, Liu Y, Liao Y, Hsiao C, et al. Mutational analysis of TBK1 in Taiwanese patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2016;40:191.e11-191.e16 pubmed publisher
    ..diagnoses of 168 patients remained elusive after mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, HNRNPA2B1, MATR3, CHCHD10, and TUBA4A had been excluded...
  32. Yasuda K, Hirohashi Y, Kuroda T, Takaya A, Kubo T, Kanaseki T, et al. MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation. Biochem Biophys Res Commun. 2016;472:643-7 pubmed publisher
    ..CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH(high)) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs...
  33. Mariani L, Tesson C, Charles P, Cazeneuve C, Hahn V, Youssov K, et al. Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach. JAMA Neurol. 2016;73:1105-14 pubmed publisher
    ..We identified mutations in genes associated with neurodegeneration, including CACNA1A (n?=?2), VPS13A (n?=?1), UBQLN2 (n?=?1), and VCP (n?=?1)...
  34. Yadav S, Singh N, Shah P, Rowbotham D, Malik D, Srivastav A, et al. MIR155 Regulation of Ubiquilin1 and Ubiquilin2: Implications in Cellular Protection and Tumorigenesis. Neoplasia. 2017;19:321-332 pubmed publisher
    ..Further, we showed that MIR155 regulates the mRNA of UBQLN1 and UBQLN2 in cells, such that increased MIR155 expression increased cell invasion, migration, wound formation and ..
  35. Liang R, Chen L, Ko B, Shen Y, Li Y, Chen B, et al. Rad23 interaction with the proteasome is regulated by phosphorylation of its ubiquitin-like (UbL) domain. J Mol Biol. 2014;426:4049-60 pubmed publisher
    ..This property is shared by structurally similar proteins (Dsk2 and Ddi1) and is conserved among the human and mouse counterparts of Rad23...
  36. Zuin A, Bichmann A, Isasa M, Puig Sàrries P, Díaz L, Crosas B. Rpn10 monoubiquitination orchestrates the association of the ubiquilin-type DSK2 receptor with the proteasome. Biochem J. 2015;472:353-65 pubmed publisher
    ..particle non-ATPase 10) and Rpn13, and the transient interactors Rad23 (radiation sensitivity abnormal 23) and Dsk2 (dual-specificity protein kinase 2), the mechanisms involved in their regulation are virtually unknown...
  37. Chuang K, Liang F, Higgins R, Wang Y. Ubiquilin/Dsk2 promotes inclusion body formation and vacuole (lysosome)-mediated disposal of mutated huntingtin. Mol Biol Cell. 2016;27:2025-36 pubmed publisher
    ..We found that yeast ubiquilin mutant (dsk2?) is sensitive to Htt103QP overexpression and has a defect in the formation of Htt103QP inclusion bodies...
  38. Le N, Chang L, Kovlyagina I, Georgiou P, Safren N, Braunstein K, et al. Motor neuron disease, TDP-43 pathology, and memory deficits in mice expressing ALS-FTD-linked UBQLN2 mutations. Proc Natl Acad Sci U S A. 2016;113:E7580-E7589 pubmed
    Missense mutations in ubiquilin 2 (UBQLN2) cause ALS with frontotemporal dementia (ALS-FTD). Animal models of ALS are useful for understanding the mechanisms of pathogenesis and for preclinical investigations...
  39. Kim T, Kim E, Yoon S, Yoon J. Herp enhances ER-associated protein degradation by recruiting ubiquilins. Biochem Biophys Res Commun. 2008;369:741-6 pubmed publisher
  40. Synofzik M, Maetzler W, Grehl T, Prudlo J, vom Hagen J, Haack T, et al. Screening in ALS and FTD patients reveals 3 novel UBQLN2 mutations outside the PXX domain and a pure FTD phenotype. Neurobiol Aging. 2012;33:2949.e13-7 pubmed publisher
    Mutations in UBQLN2 have recently been shown to cause dominant X-linked amyotrophic lateral sclerosis (ALS) and ALS plus frontotemporal dementia (FTD)...
  41. Fahed A, McDonough B, Gouvion C, Newell K, Dure L, Bebin M, et al. UBQLN2 mutation causing heterogeneous X-linked dominant neurodegeneration. Ann Neurol. 2014;75:793-798 pubmed publisher
    ..Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin-2 gene (UBQLN2) with X-linked inheritance in all studied affected individuals...
  42. Chang L, Monteiro M. Defective Proteasome Delivery of Polyubiquitinated Proteins by Ubiquilin-2 Proteins Containing ALS Mutations. PLoS ONE. 2015;10:e0130162 pubmed publisher
    ..Interest in the proteins has been heightened by the discovery that gene mutations in UBQLN2 cause dominant inheritance of amyotrophic lateral sclerosis (ALS)...
  43. Osaka M, Ito D, Suzuki N. Disturbance of proteasomal and autophagic protein degradation pathways by amyotrophic lateral sclerosis-linked mutations in ubiquilin 2. Biochem Biophys Res Commun. 2016;472:324-31 pubmed publisher
    ..Mutations in the UBQLN2 gene encoding ubiquilin 2 cause X-linked amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), and UBQLN2-positive ..
  44. Ueki N, Oda T, Kondo M, Yano K, Noguchi T, Muramatsu M. Selection system for genes encoding nuclear-targeted proteins. Nat Biotechnol. 1998;16:1338-42 pubmed
    ..We propose that NTT is an efficient method for isolating cDNAs that encode nuclear targeted proteins that can be applied to the retrieval of novel nuclear proteins and to annotate gene function. ..
  45. Kaye F, Shows T. Assignment of ubiquilin2 (UBQLN2) to human chromosome xp11. 23-->p11.1 by GeneBridge radiation hybrids. Cytogenet Cell Genet. 2000;89:116-7 pubmed
  46. Williams K, Warraich S, Yang S, Solski J, Fernando R, Rouleau G, et al. UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33:2527.e3-10 pubmed publisher
    ..Mutations in UBQLN2, which encodes ubiquilin 2, were recently identified in X-linked juvenile and adult-onset ALS and ALS/dementia...
  47. Saeki Y, Sone T, Toh e A, Yokosawa H. Identification of ubiquitin-like protein-binding subunits of the 26S proteasome. Biochem Biophys Res Commun. 2002;296:813-9 pubmed
    Ubiquitin-like proteins Rad23 and Dsk2 have recently been shown to be capable of binding both polyubiquitin chains and the 26S proteasome...
  48. Hernandez I, Espinosa A, Real L, Galan J, Mauleon A, Roca M, et al. Molecular evaluation of human ubiquilin 2 gene PXX domain in familial frontotemporal dementia patients. J Neurol. 2012;259:2488-90 pubmed publisher
  49. Millecamps S, Corcia P, Cazeneuve C, Boillee S, Seilhean D, Danel Brunaud V, et al. Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33:839.e1-3 pubmed publisher
    Mutations in UBQLN2 encoding ubiquilin-2 have recently been identified in families with dominant X-linked juvenile and adult-onset amyotrophic lateral sclerosis (ALS) and ALS/dementia...
  50. Lee D, Arnott D, Brown E. Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy machinery. EMBO Rep. 2013;14:373-81 pubmed publisher
    ..This targeting of Ubqln1 to autophagosomes requires the Ubqln4 UBL domain and the Ubqln1 UBA domain. This study identifies a new role for Ubqln4, expanding the role for Ubqlns in protein degradation. ..
  51. Tsai P, Liao Y, Chen P, Guo Y, Chen Y, Jih K, et al. Investigating CCNF mutations in a Taiwanese cohort with amyotrophic lateral sclerosis. Neurobiol Aging. 2018;62:243.e1-243.e6 pubmed publisher
    ..diagnoses of 204 patients remained unclear after mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, HNRNPA2B1, MATR3, CHCHD10, TUBA4A, and TKB1 had been investigated...
  52. Götzl J, Lang C, Haass C, Capell A. Impaired protein degradation in FTLD and related disorders. Ageing Res Rev. 2016;32:122-139 pubmed publisher
    ..FTD-linked mutations in genes encoding three autophagy adaptor proteins, p62/SQSTM1, ubiquilin 2 and optineurin, indicate that impaired autophagy might cause FTD...
  53. Picher Martel V, Valdmanis P, Gould P, Julien J, Dupré N. From animal models to human disease: a genetic approach for personalized medicine in ALS. Acta Neuropathol Commun. 2016;4:70 pubmed publisher
    ..superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others...
  54. Huang X, Shen S, Fan D. No Evidence for Pathogenic Role of UBQLN2 Mutations in Sporadic Amyotrophic Lateral Sclerosis in the Mainland Chinese Population. PLoS ONE. 2017;12:e0170943 pubmed publisher
    Mutations in the UBQLN2 gene, which encodes a member of the ubiquitin-like protein family (ubiquilin-2), have been identified in patients with dominant X-linked amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (FTD)..
  55. McLaughlin R, Kenna K, Vajda A, Byrne S, Bradley D, Hardiman O. UBQLN2 mutations are not a frequent cause of amyotrophic lateral sclerosis in Ireland. Neurobiol Aging. 2014;35:267.e9-11 pubmed publisher
    Mutations in UBQLN2 have been shown to be a cause of dominant X-linked amyotrophic lateral sclerosis (ALS). Occurrences of mutations in this gene vary across ALS populations...
  56. Kim H, Kwon M, Choi W, Oh K, Oh S, Ki C, et al. Mutations in UBQLN2 and SIGMAR1 genes are rare in Korean patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35:1957.e7-8 pubmed publisher
    Mutations in the UBQLN2 and SIGMAR1 genes were recently identified in X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS and/or FTD) and FTD and/or motor neuron disease, respectively...
  57. Osaka M, Ito D, Yagi T, Nihei Y, Suzuki N. Evidence of a link between ubiquilin 2 and optineurin in amyotrophic lateral sclerosis. Hum Mol Genet. 2015;24:1617-29 pubmed publisher
    A mutation in the ubiquilin 2 gene (UBQLN2) was recently identified as a cause of X-linked amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and a major component of the inclusion bodies commonly found with a wide variety ..
  58. Murillas R, Simms K, Hatakeyama S, Weissman A, Kuehn M. Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligase. J Biol Chem. 2002;277:2897-907 pubmed
    ..However, this protein clearly associates with Nedd4 through its PY domains and can alter the location of Nedd4 in cells, suggesting a role other than as a ubiquitylation substrate. ..
  59. Fatimababy A, Lin Y, Usharani R, Radjacommare R, Wang H, Tsai H, et al. Cross-species divergence of the major recognition pathways of ubiquitylated substrates for ubiquitin/26S proteasome-mediated proteolysis. FEBS J. 2010;277:796-816 pubmed publisher
    ..In contrast, both the RPN10 and RPN13 homologs play major roles in humans. For indirect recognition, the RAD23 and DSK2 homologs (except for the human DSK2 homolog) are major receptors...
  60. Zeng L, Wang B, Merillat S, Minakawa E, Perkins M, Ramani B, et al. Differential recruitment of UBQLN2 to nuclear inclusions in the polyglutamine diseases HD and SCA3. Neurobiol Dis. 2015;82:281-288 pubmed publisher
    ..The ubiquitin-binding and proteasome adaptor protein UBQLN2 participates in protein homeostasis and localizes to inclusions in various neurodegenerative diseases...
  61. Shimada K, Fujii T, Tatsumi Y, Anai S, Fujimoto K, Konishi N. Ubiquilin2 as a novel marker for detection of urothelial carcinoma cells in urine. Diagn Cytopathol. 2016;44:3-9 pubmed publisher
    b>Ubiquilin 2 (UBQLN2), an ubiquitin-related protein, is strongly expressed in urothelial carcinoma cells, in contrast to no or less expression in non-neoplastic cells; it protects cancer cells from reactive oxygen species (ROS)-induced ..
  62. Massey L, Mah A, Monteiro M. Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase components, Pen-2 and nicastrin. Biochem J. 2005;391:513-25 pubmed
    ..These studies implicate ubiquilin as an important factor in regulating PS biogenesis and metabolism. ..
  63. Wiggins C, Tsvetkov P, Johnson M, Joyce C, Lamb C, Bryant N, et al. BIM(EL), an intrinsically disordered protein, is degraded by 20S proteasomes in the absence of poly-ubiquitylation. J Cell Sci. 2011;124:969-77 pubmed publisher
    ..These results provide new insights into the regulation of BIM(EL) by defining a novel ubiquitin-independent pathway for the proteasome-dependent destruction of this highly toxic protein...
  64. Daoud H, Suhail H, Szuto A, Camu W, Salachas F, Meininger V, et al. UBQLN2 mutations are rare in French and French-Canadian amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33:2230.e1-2230.e5 pubmed publisher
    Mutations in the UBQLN2 gene, which encodes a member of the ubiquitin-like protein family (ubiquilin-2), have been recently identified in patients with dominant X-linked amyotrophic lateral sclerosis (ALS) and ALS with dementia...
  65. Lattante S, Le Ber I, Camuzat A, Pariente J, Brice A, Kabashi E. Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients. Neurobiol Aging. 2013;34:2078.e5-6 pubmed publisher
    ..T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. ..
  66. Xia Y, Yan L, Huang B, Liu M, Liu X, Huang C. Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and disrupts endoplasmic reticulum-associated protein degradation. J Neurochem. 2014;129:99-106 pubmed publisher
    ..How protein aggregates are formed and contribute to neurodegeneration, however, is not clear. Mutation of Ubiquilin 2 (UBQLN2) has recently been linked to ALS and frontotemporal lobar degeneration...
  67. Huang B, Wu Q, Zhou H, Huang C, Xia X. Increased Ubqln2 expression causes neuron death in transgenic rats. J Neurochem. 2016;139:285-293 pubmed publisher
    Pathogenic mutation of ubiquilin 2 (UBQLN2) causes neurodegeneration in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. How UBQLN2 mutations cause the diseases is not clear...
  68. Gellera C, Tiloca C, Del Bo R, Corrado L, Pensato V, Agostini J, et al. Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2013;84:183-7 pubmed publisher
    ..Molecular studies have recently identified different mutations in the  ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90% penetrant in women...
  69. Ugwu F, Rollinson S, Harris J, Gerhard A, Richardson A, Jones M, et al. UBQLN2 variant of unknown significance in frontotemporal lobar degeneration. Neurobiol Aging. 2015;36:546.e15-6 pubmed publisher
    ..To investigate this further, we have sequenced the ALS gene UBQLN2 in our FTD cohort and have found a single putative mutation...
  70. Tsukamoto S, Shimada K, Honoki K, Kido A, Akahane M, Tanaka Y, et al. Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress. Oncol Rep. 2015;33:1799-806 pubmed publisher
    b>Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis...
  71. Kang Y, Zhang N, Koepp D, Walters K. Ubiquitin receptor proteins hHR23a and hPLIC2 interact. J Mol Biol. 2007;365:1093-101 pubmed
    ..In addition, we demonstrate that these two proteins associate in mammalian cells. Intriguingly, inhibition of the proteasome mitigates hHR23a/hPLIC2 interaction. ..
  72. Vengoechea J, David M, Yaghi S, Carpenter L, Rudnicki S. Clinical variability and female penetrance in X-linked familial FTD/ALS caused by a P506S mutation in UBQLN2. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:615-9 pubmed publisher
    ..Clinical sequencing of UBQLN2 in a family with X-linked FTD/ALS with suspected incomplete penetrance, manifesting in both genders, revealed a ..
  73. Nölle A, van Haastert E, Zwart R, Hoozemans J, Scheper W. Ubiquilin 2 is not associated with tau pathology. PLoS ONE. 2013;8:e76598 pubmed publisher
    ..Recently, mutations in the UBQLN 2 gene encoding ubiquilin 2 have been identified in X-linked amyotrophic lateral sclerosis (ALS)...
  74. Chen X, Randles L, Shi K, Tarasov S, Aihara H, Walters K. Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 Reveal Distinct Binding Mechanisms between Substrate Receptors and Shuttle Factors of the Proteasome. Structure. 2016;24:1257-1270 pubmed publisher
    ..the proteasome bind substrates by interacting with conjugated ubiquitin chains and/or shuttle factors (Rad23/HR23, Dsk2/PLIC/ubiquilin, Ddi1) that carry ubiquitinated substrates to proteasomes...
  75. Jantrapirom S, Lo Piccolo L, Yoshida H, Yamaguchi M. A new Drosophila model of Ubiquilin knockdown shows the effect of impaired proteostasis on locomotive and learning abilities. Exp Cell Res. 2018;362:461-471 pubmed publisher
    ..Mutations in the UBQLN2 gene have been implicated in amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal lobar dementia (ALS/..
  76. Dillen L, Van Langenhove T, Engelborghs S, Vandenbulcke M, Sarafov S, Tournev I, et al. Explorative genetic study of UBQLN2 and PFN1 in an extended Flanders-Belgian cohort of frontotemporal lobar degeneration patients. Neurobiol Aging. 2013;34:1711.e1-5 pubmed publisher
    b>UBQLN2 and PFN1 were recently associated with amyotrophic lateral sclerosis (ALS). We investigated a role for these ALS genes in frontotemporal lobar degeneration (FTLD). We screened 328 FTLD, 17 FTLD-ALS, and 157 ALS patients...
  77. Gilpin K, Chang L, Monteiro M. ALS-linked mutations in ubiquilin-2 or hnRNPA1 reduce interaction between ubiquilin-2 and hnRNPA1. Hum Mol Genet. 2015;24:2565-77 pubmed publisher
    Amyotrophic lateral sclerosis (ALS)-linked mutations in UBQLN2 and some members of the heterogeneous nuclear ribonucleoproteins (hnRNPs) family cause ALS...
  78. Scotter E, Smyth L, Bailey J, Wong C, de Majo M, Vance C, et al. C9ORF72 and UBQLN2 mutations are causes of amyotrophic lateral sclerosis in New Zealand: a genetic and pathologic study using banked human brain tissue. Neurobiol Aging. 2017;49:214.e1-214.e5 pubmed publisher
    ..We show that DPR inclusions can incorporate or occur independently of ubiquilin. We also identified 1 case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions...
  79. Aguileta M, Korać J, Durcan T, Trempe J, Haber M, Gehring K, et al. The E3 ubiquitin ligase parkin is recruited to the 26 S proteasome via the proteasomal ubiquitin receptor Rpn13. J Biol Chem. 2015;290:7492-505 pubmed publisher
    ..Taken together, these findings implicate Rpn13 in linking parkin to the 26 S proteasome and regulating the clearance of mitochondrial proteins during mitophagy. ..
  80. Olbricht T. [Ubiquilin-2 immunostaining - a new marker as a diagnostic supplement in urine cytology?]. Urologe A. 2016;55:817 pubmed publisher
  81. Hjerpe R, Bett J, Keuss M, Solovyova A, McWilliams T, Johnson C, et al. UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome. Cell. 2016;166:935-949 pubmed publisher
    ..Here, we describe a new pathway for maintaining protein homeostasis mediated by the proteasome shuttle factor UBQLN2. The 26S proteasome degrades polyubiquitylated substrates by recognizing them through stoichiometrically bound ..
  82. Kleijnen M, Shih A, Zhou P, Kumar S, Soccio R, Kedersha N, et al. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell. 2000;6:409-19 pubmed
    ..Here we show that two human homologs of the yeast ubiquitin-like Dsk2 protein, hPLIC-1 and hPLIC-2, physically associate with both proteasomes and ubiquitin ligases in large complexes...
  83. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L, Shi Y, et al. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature. 2008;453:481-8 pubmed publisher
    ..Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome. ..
  84. Cassel J, Reitz A. Ubiquilin-2 (UBQLN2) binds with high affinity to the C-terminal region of TDP-43 and modulates TDP-43 levels in H4 cells: characterization of inhibition by nucleic acids and 4-aminoquinolines. Biochim Biophys Acta. 2013;1834:964-71 pubmed publisher
    Recently, it was reported that mutations in the ubiquitin-like protein ubiquilin-2 (UBQLN2) are associated with X-linked amyotrophic lateral sclerosis (ALS), and that both wild-type and mutant UBQLN2 can co-localize with aggregates of C-..
  85. Iguchi Y, Katsuno M, Ikenaka K, Ishigaki S, Sobue G. Amyotrophic lateral sclerosis: an update on recent genetic insights. J Neurol. 2013;260:2917-27 pubmed publisher
    ..structural and functional similarities to TDP-43, and physiological functions of some molecules, including VCP, UBQLN2, OPTN, FIG4 and SQSTM1, are involved in a protein degradation system...
  86. Itakura E, Zavodszky E, Shao S, Wohlever M, Keenan R, Hegde R. Ubiquilins Chaperone and Triage Mitochondrial Membrane Proteins for Degradation. Mol Cell. 2016;63:21-33 pubmed publisher
    ..These findings define Ubiquilins as a family of chaperones for cytosolically exposed transmembrane domains and explain how they use ubiquitin to triage clients for degradation via coordinated intra- and intermolecular interactions. ..
  87. Nolan T, Brennan B, Yang M, Chen J, Zhang M, Li Z, et al. Selective Autophagy of BES1 Mediated by DSK2 Balances Plant Growth and Survival. Dev Cell. 2017;41:33-46.e7 pubmed publisher
    ..Here, we show that BES1 interacts with the ubiquitin receptor protein DSK2 and is targeted to the autophagy pathway during stress via the interaction of DSK2 with ATG8, a ubiquitin-like ..
  88. Kaye F, Modi S, Ivanovska I, Koonin E, Thress K, Kubo A, et al. A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch. FEBS Lett. 2000;467:348-55 pubmed
    ..b>Chap1 is a duplicated homologue of the yeast Dsk2 gene that is required for transit through the G2/M phase of the cell ..
  89. N Diaye E, Hanyaloglu A, Kajihara K, Puthenveedu M, Wu P, von Zastrow M, et al. The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-coupled receptor endocytosis. Mol Biol Cell. 2008;19:1252-60 pubmed publisher
    ..Identification of a negative regulator of GPCR clustering reveals a new function of ubiquitin-like proteins and highlights a cellular requirement for exquisite regulation of receptor dynamics. ..
  90. van Doormaal P, van Rheenen W, van Blitterswijk M, Schellevis R, Schelhaas H, de Visser M, et al. UBQLN2 in familial amyotrophic lateral sclerosis in The Netherlands. Neurobiol Aging. 2012;33:2233.e7-2233.e8 pubmed publisher
    Recently it was discovered that mutations in the UBQLN2 gene were a cause of an X-linked dominant type of familial amyotrophic lateral sclerosis (ALS)...
  91. Walters K, Kleijnen M, Goh A, Wagner G, Howley P. Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a. Biochemistry. 2002;41:1767-77 pubmed
    ..This study provides structural insights into protein recognition by the proteasome, and illustrates how the protein surface of a commonly utilized fold has highly evolved for various biological roles. ..