Gene Symbol: UBA1
Description: ubiquitin like modifier activating enzyme 1
Alias: A1S9, A1S9T, A1ST, AMCX1, CFAP124, GXP1, POC20, SMAX2, UBA1A, UBE1, UBE1X, ubiquitin-like modifier-activating enzyme 1, A1S9T and BN75 temperature sensitivity complementing, POC20 centriolar protein homolog, UBA1, ubiquitin-activating enzyme E1 homolog A, testicular secretory protein Li 63
Species: human
Products:     UBA1

Top Publications

  1. Brès V, Kiernan R, Linares L, Chable Bessia C, Plechakova O, Treand C, et al. A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Nat Cell Biol. 2003;5:754-61 pubmed
    ..Fusion of ubiquitin to Tat bypasses the requirement of Hdm2 for efficient transactivation, supporting the notion that ubiquitin has a non-proteolytic function in Tat-mediated transactivation. ..
  2. Leidecker O, Matic I, Mahata B, Pion E, Xirodimas D. The ubiquitin E1 enzyme Ube1 mediates NEDD8 activation under diverse stress conditions. Cell Cycle. 2012;11:1142-50 pubmed publisher
    ..Here, we present the unexpected finding that under stress conditions, the ubiquitin E1 enzyme Ube1 mediates conjugation of the ubiquitin-like molecule NEDD8...
  3. Canning M, Boutell C, Parkinson J, Everett R. A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7. J Biol Chem. 2004;279:38160-8 pubmed
    ..This principle may extend to a number of cellular RING finger E3 ubiquitin ligase proteins that have analogous interactions with ubiquitin-specific cleavage enzymes. ..
  4. Pelzer C, Kassner I, Matentzoglu K, Singh R, Wollscheid H, Scheffner M, et al. UBE1L2, a novel E1 enzyme specific for ubiquitin. J Biol Chem. 2007;282:23010-4 pubmed
    b>UBE1 is known as the human ubiquitin-activating enzyme (E1), which activates ubiquitin in an ATP-dependent manner...
  5. Jin J, Li X, Gygi S, Harper J. Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging. Nature. 2007;447:1135-8 pubmed
    ..adenylation and thioesterification of the carboxy-terminal carboxylate of ubiquitin by the E1-activating enzyme Ube1 (Uba1 in yeast), followed by ubiquitin transfer to an E2-conjugating enzyme through a transthiolation reaction...
  6. Gavin J, Chen J, Liao H, Rollins N, Yang X, Xu Q, et al. Mechanistic studies on activation of ubiquitin and di-ubiquitin-like protein, FAT10, by ubiquitin-like modifier activating enzyme 6, Uba6. J Biol Chem. 2012;287:15512-22 pubmed publisher
    Uba6 is a homolog of the ubiquitin-activating enzyme, Uba1, and activates two ubiquitin-like proteins (UBLs), ubiquitin and FAT10...
  7. Rani N, Aichem A, Schmidtke G, Kreft S, Groettrup M. FAT10 and NUB1L bind to the VWA domain of Rpn10 and Rpn1 to enable proteasome-mediated proteolysis. Nat Commun. 2012;3:749 pubmed publisher
    ..In conclusion, we identify the VWA domain of hRpn10 as a receptor for ubiquitin-like proteins within the 26S proteasome and elucidate how FAT10 mediates efficient proteolysis by the proteasome. ..
  8. Moudry P, Lukas C, Macurek L, Hanzlikova H, Hodny Z, Lukas J, et al. Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage. Cell Cycle. 2012;11:1573-82 pubmed publisher
    ..Here, we identify ubiquitin-activating enzyme UBA1 as the E1 enzyme required for responses to IR and replication stress in human cells...
  9. Aichem A, Kalveram B, Spinnenhirn V, Kluge K, Catone N, Johansen T, et al. The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation. J Cell Sci. 2012;125:4576-85 pubmed publisher
    ..USE1 which auto-FAT10ylates itself in cis, the tumor suppressor p53 and the ubiquitin-activating enzyme UBE1 (UBA1)...

More Information

Publications164 found, 100 shown here

  1. Yang U, Yang H, Kim J, Lee T. The functional role of UBA1 cysteine-278 in ubiquitination. Biochem Biophys Res Commun. 2012;427:587-92 pubmed publisher
    Although total UBA1 levels were unchanged, after oxidation for 60 min, we observed dramatic changes in the levels of BIAM-labeled UBA1 in both the membrane and cytosol fractions that suggested oxidative stress induces translocation of ..
  2. Mizushima N, Sugita H, Yoshimori T, Ohsumi Y. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem. 1998;273:33889-92 pubmed
    ..These findings indicate that the Apg12 system is well conserved and may function in autophagy also in human cells. ..
  3. Hyka Nouspikel N, Lemonidis K, Lu W, Nouspikel T. Circulating human B lymphocytes are deficient in nucleotide excision repair and accumulate mutations upon proliferation. Blood. 2011;117:6277-86 pubmed publisher
    ..NER attenuation in quiescent cells is associated with incomplete phosphorylation of the ubiquitin activating enzyme Ube1, which is required for proficient NER...
  4. Dlamini N, Josifova D, Paine S, Wraige E, Pitt M, Murphy A, et al. Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene. Neuromuscul Disord. 2013;23:391-8 pubmed publisher
    Infantile-onset X-linked spinal muscular atrophy (SMAX2) is a rare lethal disorder linked to mutations in the UBA1 (previously UBE1) gene, encoding ubiquitin-activating enzyme 1 that has an important role in the ubiquitin-proteasome ..
  5. Lee P, Dodart J, Aron L, Finley L, Bronson R, Haigis M, et al. Altered social behavior and neuronal development in mice lacking the Uba6-Use1 ubiquitin transfer system. Mol Cell. 2013;50:172-84 pubmed publisher
    ..the ubiquitin proteasome system (UPS) and is required for mouse embryonic development, independent of the canonical Uba1-E2-E3 pathway...
  6. Chang T, Shravage B, Hayes S, Powers C, Simin R, Wade Harper J, et al. Uba1 functions in Atg7- and Atg3-independent autophagy. Nat Cell Biol. 2013;15:1067-78 pubmed publisher
    ..Rather, Uba1, the E1 enzyme used in ubiquitylation, is required for autophagy and reduction of cell size...
  7. Kumar S, Kao W, Howley P. Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity. J Biol Chem. 1997;272:13548-54 pubmed
  8. Kanlaya R, Pattanakitsakul S, Sinchaikul S, Chen S, Thongboonkerd V. The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells. J Proteome Res. 2010;9:4960-71 pubmed publisher
    ..The proteomic data were validated by Western blot analyses [upregulated ubiquitin-activating enzyme E1 (UBE1) and downregulated annexin A2] and an immunofluorescence study (upregulated MxA)...
  9. Liu H, Pfleger C. Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment. PLoS ONE. 2013;8:e32835 pubmed publisher
    ..the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway...
  10. Albrecht D, Hürlimann H, Ceschin J, Saint Marc C, Pinson B, Daignan Fornier B. Multiple chemo-genetic interactions between a toxic metabolite and the ubiquitin pathway in yeast. Curr Genet. 2018;64:1275-1286 pubmed publisher
    ..we found that ZMP accumulation is synthetic lethal with a hypomorphic allele of the ubiquitin-activating enzyme Uba1. A search for gene-dosage suppressors revealed that ubiquitin overexpression was sufficient to restore growth of ..
  11. Metzger M, Liang Y, Das R, Mariano J, Li S, Li J, et al. A structurally unique E2-binding domain activates ubiquitination by the ERAD E2, Ubc7p, through multiple mechanisms. Mol Cell. 2013;50:516-27 pubmed publisher
    ..This demonstrates that an essential component of E3 complexes can simultaneously bind to E2 and enhance its loading with ubiquitin. These findings provide mechanistic insights into how ubiquitination can be stimulated. ..
  12. Mathew A, Mathur S, Morimoto R. Heat shock response and protein degradation: regulation of HSF2 by the ubiquitin-proteasome pathway. Mol Cell Biol. 1998;18:5091-8 pubmed
  13. Wishart T, Paterson J, Short D, Meredith S, Robertson K, Sutherland C, et al. Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Mol Cell Proteomics. 2007;6:1318-30 pubmed
    ..we show that downstream protein changes can be identified in pathways corresponding to both Ube4b (including UBE1) and Nmnat1 (including VDAC1 and Aralar1) components of the chimeric Wld(s) gene, suggesting that full-length Wld(s)..
  14. Anding A, Wang C, Chang T, Sliter D, Powers C, Hofmann K, et al. Vps13D Encodes a Ubiquitin-Binding Protein that Is Required for the Regulation of Mitochondrial Size and Clearance. Curr Biol. 2018;28:287-295.e6 pubmed publisher
    ..reduction in cell size and clearance of mitochondria that depends on autophagy, the E1 ubiquitin-activating enzyme Uba1, and ubiquitin [2]...
  15. Lv Z, Williams K, Yuan L, Atkison J, Olsen S. Crystal structure of a human ubiquitin E1-ubiquitin complex reveals conserved functional elements essential for activity. J Biol Chem. 2018;293:18337-18352 pubmed publisher
    ..of the hUBA1 mechanism, provides an improved framework for the development of small-molecule inhibitors of UBA1, and serves as a stepping stone for structural studies that involve the enzymes of the human Ub system at the level ..
  16. Hu M, Li P, Song L, Jeffrey P, Chenova T, Wilkinson K, et al. Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 2005;24:3747-56 pubmed
    ..These structural observations, in conjunction with biochemical characterization, identify important regulatory mechanisms for USP14. ..
  17. Jedrzejowska M, Jakubowska Pietkiewicz E, Kostera Pruszczyk A. X-linked spinal muscular atrophy (SMAX2) caused by de novo c.1731C>T substitution in the UBA1 gene. Neuromuscul Disord. 2015;25:661-6 pubmed publisher
    Infantile X-linked spinal muscular atrophy (SMAX2) is a rare form of spinal muscular atrophy manifesting as severe hypotonia, areflexia, arthrogryposis, facial weakness and cryptorchidism, and frequently accompanied by bone fractures...
  18. Liu X, Zhao B, Sun L, Bhuripanyo K, Wang Y, Bi Y, et al. Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes. Nat Commun. 2017;8:14286 pubmed publisher
    ..b>Uba1 was thought to be the only E1 until the recent identification of Uba6...
  19. Stephen A, Trausch Azar J, Ciechanover A, Schwartz A. The ubiquitin-activating enzyme E1 is phosphorylated and localized to the nucleus in a cell cycle-dependent manner. J Biol Chem. 1996;271:15608-14 pubmed
  20. Kentsis A, Gordon R, Borden K. Control of biochemical reactions through supramolecular RING domain self-assembly. Proc Natl Acad Sci U S A. 2002;99:15404-9 pubmed
    ..These studies reveal a general paradigm of how supramolecular structures may function in cells. ..
  21. Chen C, Meng Y, Wang L, Wang H, Tian C, Pang G, et al. Ubiquitin-activating enzyme E1 inhibitor PYR41 attenuates angiotensin II-induced activation of dendritic cells via the I?Ba/NF-?B and MKP1/ERK/STAT1 pathways. Immunology. 2014;142:307-19 pubmed publisher
    ..Ubiquitin-activating enzyme (E1/Uba1) is the common first step in ubiquitylation, which decides whether or not the modified protein is ultimately ..
  22. Jacobson A, Macfadden A, Wu Z, Peng J, Liu C. Autoregulation of the 26S proteasome by in situ ubiquitination. Mol Biol Cell. 2014;25:1824-35 pubmed publisher
    ..We propose that in situ ubiquitination of the 26S proteasome regulates its activity, which could function to adjust proteasomal activity in response to the alteration of cellular ubiquitination levels. ..
  23. Carbia Nagashima A, Gerez J, Perez Castro C, Paez Pereda M, Silberstein S, Stalla G, et al. RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell. 2007;131:309-23 pubmed
    ..Together, these findings point to a central role of RSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells. ..
  24. Zhang L, Fairall L, Goult B, Calkin A, Hong C, Millard C, et al. The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. Genes Dev. 2011;25:1262-74 pubmed publisher
    ..These results identify the IDOL-UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake. ..
  25. Zhao B, Bhuripanyo K, Schneider J, Zhang K, Schindelin H, Boone D, et al. Specificity of the E1-E2-E3 enzymatic cascade for ubiquitin C-terminal sequences identified by phage display. ACS Chem Biol. 2012;7:2027-35 pubmed publisher
    ..In this study, we used phage display to profile the specificity of the two human E1 enzymes, Ube1 and Uba6, toward the C-terminal sequence of UB ending with (71)LRLRGG(76)...
  26. Huang T, Lehmann M, Said A, Ma G, Osterrieder N. Major histocompatibility complex class I downregulation induced by equine herpesvirus type 1 pUL56 is through dynamin-dependent endocytosis. J Virol. 2014;88:12802-15 pubmed publisher
    ..Finally, pUL56 action extends to a number of cell surface molecules that are significant for host immunity. Therefore, the protein may exert a more general immunomodulatory effect. ..
  27. Butnaru C, Chiritoiu M, Chiritoiu G, Petrescu S, Petrescu A. Inhibition of N-glycan processing modulates the network of EDEM3 interactors. Biochem Biophys Res Commun. 2017;486:978-984 pubmed publisher
    ..involved in the ERAD cargo recognition and targeting to degradation translocation into the cytosol, including UBA1 and UBA2 ubiquitinating enzymes...
  28. Peng C, Yang Q, Wei B, Liu Y, Li Y, Gu D, et al. Identification of potential target genes and related regulatory transcription factors in spontaneous hairline fracture induced by hypervitaminosis A. Injury. 2017;48:1475-1479 pubmed publisher
    ..Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A...
  29. Asuthkar S, Velpula K, Elustondo P, Demirkhanyan L, Zakharian E. TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells. Oncotarget. 2015;6:17221-36 pubmed
    ..analysis of TRPM8, immunoprecipitated from LNCaP cells identified ubiquitin-like modifier-activating enzyme 1 (UBA1)...
  30. Bridgford J, Xie S, Cobbold S, Pasaje C, Herrmann S, Yang T, et al. Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome. Nat Commun. 2018;9:3801 pubmed publisher
  31. Garcia Caballero A, Gadotti V, Chen L, Zamponi G. A cell-permeant peptide corresponding to the cUBP domain of USP5 reverses inflammatory and neuropathic pain. Mol Pain. 2016;12: pubmed publisher
    ..for the interaction, we used a series of USP5-derived peptides corresponding to different regions in nUBP, cUBP, UBA1, and UBA2 domains to outcompete full length USP5...
  32. Smith G, Fearnley G, Abdul Zani I, Wheatcroft S, Tomlinson D, Harrison M, et al. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function. Biol Open. 2017;6:1404-1415 pubmed publisher
    ..Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated ..
  33. Srivenugopal K, Yuan X, Friedman H, Ali Osman F. Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltransferase in human and murine tumor cells following inactivation with O6-benzylguanine or 1,3-bis(2-chloroethyl)-1-nitrosourea. Biochemistry. 1996;35:1328-34 pubmed
    ..These results provide conclusive evidence that the MGMT protein, following its inactivation, is degraded via the ubiquitin proteolytic pathway. ..
  34. Anindya R, Aygün O, Svejstrup J. Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Mol Cell. 2007;28:386-97 pubmed
    ..Nedd4-dependent RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together, our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment and RNAPII ubiquitylation. ..
  35. Wang X, Shi Y, Wang J, Huang G, Jiang X. Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation. Biochem J. 2008;414:221-9 pubmed publisher
  36. Perez Patiño C, Parrilla I, Barranco I, Vergara Barberán M, Simó Alfonso E, Herrero Martínez J, et al. New In-Depth Analytical Approach of the Porcine Seminal Plasma Proteome Reveals Potential Fertility Biomarkers. J Proteome Res. 2018;17:1065-1076 pubmed publisher
    ..penalized linear regression LASSO revealed differentially expressed SP proteins for farrowing rate (FURIN, AKR1B1, UBA1, PIN1, SPAM1, BLMH, SMPDL3A, KRT17, KRT10, TTC23, and AGT) and litter size (PN-1, THBS1, DSC1, and CAT)...
  37. Shu Q, Lai S, Wang X, Zhang Y, Yang X, Bi H, et al. Administration of ubiquitin-activating enzyme UBA1 inhibitor PYR-41 attenuates angiotensin II-induced cardiac remodeling in mice. Biochem Biophys Res Commun. 2018;505:317-324 pubmed publisher
    ..However, the functional role of E1 (UBA1) in regulation of hypertrophic remodeling in angiotensin II (Ang II)-infused mice remains unknown...
  38. Fuller H, Gillingwater T, Wishart T. Commonality amid diversity: Multi-study proteomic identification of conserved disease mechanisms in spinal muscular atrophy. Neuromuscul Disord. 2016;26:560-9 pubmed publisher
    ..analysis of distinct proteomic datasets reveals conserved changes in pathways converging on GAP43, GAPDH, NCAM, UBA1, LMNA, ANXA2 and COL6A3...
  39. Zhang C, Chen Y, Gan X, Huang Z, Zou M, Fu W, et al. SAK-HV Decreases the Self-Ubiquitination of MEKK1 to Promote Macrophage Proliferation via MAPK/ERK and JNK Pathways. Int J Mol Sci. 2017;18: pubmed publisher
    ..We screened out Uba1 as the SAK-HV-interacting protein in the RAW264...
  40. Kumar B, Lecompte K, Klein J, Haas A. Ser(120) of Ubc2/Rad6 regulates ubiquitin-dependent N-end rule targeting by E3{alpha}/Ubr1. J Biol Chem. 2010;285:41300-9 pubmed publisher
    ..These studies suggest a mechanism for the integrated regulation of diverse ubiquitin-dependent signaling pathways through E2 phosphorylation that yields differential effects on its cognate ligases. ..
  41. Pao K, Wood N, Knebel A, Rafie K, Stanley M, Mabbitt P, et al. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Nature. 2018;556:381-385 pubmed publisher
    ..These findings implicate non-lysine ubiquitination in cellular regulation of higher eukaryotes and suggest that E3 enzymes have an unappreciated mechanistic diversity. ..
  42. E Y, Yuan J, Yang F, Wang L, Ma J, Li J, et al. PGPR strain Paenibacillus polymyxa SQR-21 potentially benefits watermelon growth by re-shaping root protein expression. AMB Express. 2017;7:104 pubmed publisher
    ..The results of this study indicated that SQR-21 inoculation on the watermelon roots benefits plant by inducing the expression of several proteins involved in growth, photosynthesis, and other metabolic and physiological activities. ..
  43. Bialas J, Groettrup M, Aichem A. Conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation. PLoS ONE. 2015;10:e0120329 pubmed publisher
    ..By mass spectrometry analysis the ubiquitin E1 activating enzyme ubiquitin-activating enzyme 1 (UBE1) was identified as putative substrate of FAT10...
  44. Misra M, Kuhn M, Löbel M, An H, Statsyuk A, Sotriffer C, et al. Dissecting the Specificity of Adenosyl Sulfamate Inhibitors Targeting the Ubiquitin-Activating Enzyme. Structure. 2017;25:1120-1129.e3 pubmed publisher
    ..Here, we report crystal structures of the yeast ubiquitin E1 (Uba1) with three adenosyl sulfamate inhibitors exhibiting different E1 specificities, which are all covalently linked to ..
  45. Choi M, Chun J, Kwak S, Bang S, Jin Y, Lee Y, et al. Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome. Toxicol Appl Pharmacol. 2018;355:68-79 pubmed publisher
    ..We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR...
  46. Ye C, Tang H, Zhao Z, Lei C, You C, Zhang J, et al. MDM2 mediates fibroblast activation and renal tubulointerstitial fibrosis via a p53-independent pathway. Am J Physiol Renal Physiol. 2017;312:F760-F768 pubmed publisher
    ..Taken together, our findings provide the first evidence that MDM2 is involved in fibroblast activation and TIF, which associates with Notch1 ubiquitination and proteasome degradation. ..
  47. Das R, Mariano J, Tsai Y, Kalathur R, Kostova Z, Li J, et al. Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Mol Cell. 2009;34:674-85 pubmed publisher
    ..These findings uncover a mechanism whereby allosteric effects on an E2 enhance E2-RING finger interactions and, consequently, ubiquitylation. ..
  48. Barghout S, Patel P, Wang X, Xu G, Kavanagh S, Halgas O, et al. Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia. Leukemia. 2019;33:37-51 pubmed publisher
    ..One such potential therapeutic strategy is to target the ubiquitin-like modifier-activating enzyme 1 (UBA1), the initiating enzyme in the ubiquitylation cascade in which proteins are tagged with ubiquitin moieties to ..
  49. Li S, Izumi T, Hu J, Jin H, Siddiqui A, Jacobson S, et al. Rescue of enzymatic function for disease-associated RPE65 proteins containing various missense mutations in non-active sites. J Biol Chem. 2014;289:18943-56 pubmed publisher
  50. Koszela J, Pham N, Evans D, Mann S, Pérez Pi I, Shave S, et al. Real-time tracking of complex ubiquitination cascades using a fluorescent confocal on-bead assay. BMC Biol. 2018;16:88 pubmed publisher
    ..We demonstrate the power of the UPS-CONA technique by simultaneously following ubiquitin transfer from Ube1 through Ube2L3 to E6AP...
  51. Mitchell M, Wilcox S, Watson J, Lerner J, Woods D, Scheffler J, et al. The origin and loss of the ubiquitin activating enzyme gene on the mammalian Y chromosome. Hum Mol Genet. 1998;7:429-34 pubmed
    ..One well-studied example of an X-Y homologous gene is the ubiquitin activating enzyme gene ( UBE1 ), which is X-linked with a distinct Y-linked gene in many eutherian ('placental') and metatherian (marsupial) ..
  52. Kerns K, Morales P, Sutovsky P. Regulation of Sperm Capacitation by the 26S Proteasome: An Emerging New Paradigm in Spermatology. Biol Reprod. 2016;94:117 pubmed publisher
    ..The E1-type ubiquitin-activating enzyme (UBA1) inhibitor PYR-41 also alters acrosomal membrane remodeling during capacitation...
  53. Lv Z, Rickman K, Yuan L, Williams K, Selvam S, Woosley A, et al. S. pombe Uba1-Ubc15 Structure Reveals a Novel Regulatory Mechanism of Ubiquitin E2 Activity. Mol Cell. 2017;65:699-714.e6 pubmed publisher
    ..Here, we report the structure of S. pombe Uba1 in complex with Ubc15, a Ub E2 with intrinsically low E1-E2 Ub thioester transfer activity...
  54. Nouspikel T, Hanawalt P. Impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme. Proc Natl Acad Sci U S A. 2006;103:16188-93 pubmed
    ..quot; ..
  55. Zhang C, Song L, Choudhary M, Zhou B, Sun G, Broderick K, et al. Genome-wide analysis of genes encoding core components of the ubiquitin system in soybean (Glycine max) reveals a potential role for ubiquitination in host immunity against soybean cyst nematode. BMC Plant Biol. 2018;18:149 pubmed publisher
    ..This study sets up an essential foundation for further functional characterization of the soybean UBS in various physiological processes, such as host immunity against SCN. ..
  56. Chen A, Kleiman F, Manley J, Ouchi T, Pan Z. Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase. J Biol Chem. 2002;277:22085-92 pubmed
    ..These results raise the possibility that BRCA1*BARD1 acts to assemble non-lysine 48-linked polyubiquitin chains that may serve as part of a signaling platform required for coordinating DNA repair-related events. ..
  57. Tokgöz Z, Siepmann T, Streich F, Kumar B, Klein J, Haas A. E1-E2 interactions in ubiquitin and Nedd8 ligation pathways. J Biol Chem. 2012;287:311-21 pubmed publisher
    ..A functional survey of 11 representative human E2 paralogs reveals similar Km for binding to human Uba1 ternary complex (Km(ave)=121±72 nm) and kcat for ubiquitin transfer (kcat(ave)=4.0±1...
  58. Song A, Yang H, Gao Y, Zhou C, Zhang Y, Hu H. A ubiquitin shuttle DC-UbP/UBTD2 reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes. PLoS ONE. 2014;9:e107509 pubmed publisher
    ..We identified two Ub-related enzymes, the deubiquitinating enzyme USP5 and the Ub-activating enzyme UbE1, as interacting partners of DC-UbP from HEK 293T cells...
  59. Dennis K, Valentine W. Ziram and sodium N,N-dimethyldithiocarbamate inhibit ubiquitin activation through intracellular metal transport and increased oxidative stress in HEK293 cells. Chem Res Toxicol. 2015;28:682-90 pubmed publisher
    ..These studies suggest that E1 is a sensitive redox sensor that can be modulated by exposure to environmental agents and can regulate downstream cellular processes. ..
  60. Powis R, Karyka E, Boyd P, Côme J, Jones R, Zheng Y, et al. Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy. JCI Insight. 2016;1:e87908 pubmed publisher
    ..SMN depletion, by increasing levels of one key ubiquitination enzyme (ubiquitin-like modifier activating enzyme 1 [UBA1]), represents a viable approach for treating SMA...
  61. Ravindran R, Polk P, Robinson L, Tatchell K. New ubiquitin-dependent mechanisms regulating the Aurora B-protein phosphatase 1 balance in Saccharomyces cerevisiae. J Cell Sci. 2018;131: pubmed publisher
    ..We report here a novel mutation altering the Saccharomyces cerevisiae E1 ubiquitin-activating enzyme (uba1-W928R) that suppresses the temperature sensitivity and chromosome loss phenotype of a well-characterized Aurora ..
  62. Necchi V, Sommi P, Ricci V, Solcia E. In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure. PLoS ONE. 2010;5:e9716 pubmed publisher
  63. Samuel W, Kutty R, Duncan T, Vijayasarathy C, Kuo B, Chapa K, et al. Fenretinide induces ubiquitin-dependent proteasomal degradation of stearoyl-CoA desaturase in human retinal pigment epithelial cells. J Cell Physiol. 2014;229:1028-38 pubmed publisher
    ..Therefore, the effect of fenretinide on SCD should be considered in its potential therapeutic role against cancer, type-2 diabetes, and retinal diseases. ..
  64. Pisano A, Ceglia S, Palmieri C, Vecchio E, Fiume G, De Laurentiis A, et al. CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation. J Biol Chem. 2015;290:13958-71 pubmed publisher
    ..By characterizing CRL3(IBTK) as a novel ubiquitin ligase, this study provides new insights into regulatory mechanisms of cellular pathways, such as the Pdcd4-dependent translation of mRNAs. ..
  65. Fan J, Miyauchi Ishida S, Arimoto K, Liu D, Yan M, Liu C, et al. Type I IFN induces protein ISGylation to enhance cytokine expression and augments colonic inflammation. Proc Natl Acad Sci U S A. 2015;112:14313-8 pubmed publisher
  66. Jain J, Jain S, Walker L, Tekwani B. Inhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads. BMC Pharmacol Toxicol. 2017;18:40 pubmed publisher
  67. Wu P, Hanlon M, Eddins M, Tsui C, Rogers R, Jensen J, et al. A conserved catalytic residue in the ubiquitin-conjugating enzyme family. EMBO J. 2003;22:5241-50 pubmed
    ..We propose that the conserved asparagine side chain stabilizes the oxyanion intermediate formed during lysine attack. The E2 asparagine is the first non-covalent catalytic group to be proposed in any Ub conjugation factor. ..
  68. Itoh Y, Suzuki M. Design, synthesis, and biological evaluation of novel ubiquitin-activating enzyme inhibitors. Bioorg Med Chem Lett. 2018;28:2723-2727 pubmed publisher
    ..Compound 4b increased p53 levels in MCF-7 breast cancer cells and inhibited their growth. These findings suggest that reversible E1 inhibitors are potential anticancer agents. ..
  69. Tokgöz Z, Bohnsack R, Haas A. Pleiotropic effects of ATP.Mg2+ binding in the catalytic cycle of ubiquitin-activating enzyme. J Biol Chem. 2006;281:14729-37 pubmed
    ..The latter mechanistic effect explicates the observed loss-of-function phenotype associated with mutation of residues paralogous to Asp(576) within the activating enzymes for other ubiquitin-like proteins. ..
  70. Colin J, Garibal J, Clavier A, Rincheval Arnold A, Gaumer S, Mignotte B, et al. The drosophila Bcl-2 family protein Debcl is targeted to the proteasome by the β-TrCP homologue slimb. Apoptosis. 2014;19:1444-56 pubmed publisher
    ..identify regulators of mammalian bax-induced apoptosis in Drosophila, we identified the ubiquitin activating enzyme Uba1 as a suppressor of bax-induced cell death...
  71. Shruthi K, Reddy S, Reddy G. Ubiquitin-proteasome system and ER stress in the retina of diabetic rats. Arch Biochem Biophys. 2017;627:10-20 pubmed publisher
    ..The declined UPS components: E1 and HRD1 in the retina of diabetic rats could elicit ER stress, and the prolonged ER stress may trigger CHOP-mediated neuronal apoptosis. ..
  72. Adam K, Lambert M, Lestang E, Champenois G, Dusanter Fourt I, Tamburini J, et al. Control of Pim2 kinase stability and expression in transformed human haematopoietic cells. Biosci Rep. 2015;35: pubmed publisher
    ..We show that Pim2 inhibitors and proteasome inhibitors, such as bortezomib, have additive effects to inhibit the growth of myeloma cells, suggesting that Pim2 could be an interesting target for the treatment of multiple myeloma. ..
  73. Barriere H, Nemes C, Du K, Lukacs G. Plasticity of polyubiquitin recognition as lysosomal targeting signals by the endosomal sorting machinery. Mol Biol Cell. 2007;18:3952-65 pubmed
  74. Lin A, Guttman J. The Escherichia coli adherence factor plasmid of enteropathogenic Escherichia coli causes a global decrease in ubiquitylated host cell proteins by decreasing ubiquitin E1 enzyme expression through host aspartyl proteases. Int J Biochem Cell Biol. 2012;44:2223-32 pubmed publisher
    ..coli to inactivate host protein ubiquitylation could enable more efficient effector protein functionality, providing increased bacterial control of host cells during enteropathogenic E. coli pathogenesis. ..
  75. Yurchenko V, Xue Z, Sadofsky M. The RAG1 N-terminal domain is an E3 ubiquitin ligase. Genes Dev. 2003;17:581-5 pubmed
    ..This finding suggests a new way in which V(D)J recombination can be regulated and coupled to other aspects of cell physiology. ..
  76. Chen L, Madura K. Evidence for distinct functions for human DNA repair factors hHR23A and hHR23B. FEBS Lett. 2006;580:3401-8 pubmed
    ..We also determined that hHR23A and hHR23B could be co-purified with unique proteolytic and stress-responsive factors from human breast cancer tissues, indicating that they have unique functions in vivo. ..
  77. Kudo M, Sugasawa K, Hori T, Enomoto T, Hanaoka F, Ui M. Human ubiquitin-activating enzyme (E1): compensation for heat-labile mouse E1 and its gene localization on the X chromosome. Exp Cell Res. 1991;192:110-7 pubmed
    ..Thus we conclude that the functional gene for human E1 is located on the X chromosome. ..
  78. Umebayashi K, Stenmark H, Yoshimori T. Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation. Mol Biol Cell. 2008;19:3454-62 pubmed publisher
    ..We propose that sustained tyrosine phosphorylation of EGFR facilitates its polyubiquitination in endosomes and counteracts rapid deubiquitination, thereby ensuring Hrs-dependent lysosomal sorting. ..
  79. Wang R, Zhang P, Li J, Guan H, Shi G. Ubiquitination is absolutely required for the degradation of hypoxia-inducible factor--1 alpha protein in hypoxic conditions. Biochem Biophys Res Commun. 2016;470:117-122 pubmed publisher
    ..Further inhibition of E1 at 39.5 °C by siRNA, or E1 inhibitor Ube1-41 completely blocked HIF-1? degradation...
  80. Qin Z, Cui B, Jin J, Song M, Zhou B, Guo H, et al. The ubiquitin-activating enzyme E1 as a novel therapeutic target for the treatment of restenosis. Atherosclerosis. 2016;247:142-53 pubmed publisher
    The ubiquitin-activating enzyme E1 (UBA1, E1), the apex of the ubiquitin proteasome pathway, plays a critical role in protein degradation and in pathological processes...
  81. Wang S, Juan J, Zhang Z, Du Y, Xu Y, Tong J, et al. Inhibition of the deubiquitinase USP5 leads to c-Maf protein degradation and myeloma cell apoptosis. Cell Death Dis. 2017;8:e3058 pubmed publisher
    ..and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
  82. Yoshida K, Kang W, Nakamura A, Kawano N, Hanai M, Miyado M, et al. Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg. Reprod Toxicol. 2018;76:71-77 pubmed publisher
    The ubiquitin-proteasome system, which is initiated by a single ubiquitin-activating enzyme E1 (UBE1), is involved in male reproduction via spermatogenesis and function in mammals...
  83. Yi Y, Manandhar G, Sutovsky M, Jonáková V, Park C, Sutovsky P. Inhibition of 19S proteasomal regulatory complex subunit PSMD8 increases polyspermy during porcine fertilization in vitro. J Reprod Immunol. 2010;84:154-63 pubmed publisher
  84. Xie S. Expression, purification, and crystal structure of N-terminal domains of human ubiquitin-activating enzyme (E1). Biosci Biotechnol Biochem. 2014;78:1542-9 pubmed publisher
    ..The main structure of both IAD and FCCH superimposed well with their corresponding domains in yeast Uba1, but their relative positions vary significantly...
  85. Bellesi M, de Vivo L, Tononi G, Cirelli C. Effects of sleep and wake on astrocytes: clues from molecular and ultrastructural studies. BMC Biol. 2015;13:66 pubmed publisher
    ..Sleep upregulates a few select genes, like Cirp and Uba1, whereas wake upregulates many genes related to metabolism, the extracellular matrix and cytoskeleton, including ..
  86. Zhu Z, Yang F, Zhang K, Cao W, Jin Y, Wang G, et al. Comparative Proteomic Analysis of Wild-Type and SAP Domain Mutant Foot-and-Mouth Disease Virus-Infected Porcine Cells Identifies the Ubiquitin-Activating Enzyme UBE1 Required for Virus Replication. J Proteome Res. 2015;14:4194-206 pubmed publisher
    ..One of the identified proteins UBE1 was further analyzed and displayed a novel role for the SAP domain of L(pro)...
  87. Zacksenhaus E, Sheinin R. Molecular cloning, primary structure and expression of the human X linked A1S9 gene cDNA which complements the ts A1S9 mouse L cell defect in DNA replication. EMBO J. 1990;9:2923-9 pubmed
    The temperature-sensitive ts A1S9 mutation of mouse L cells was previously shown to affect nuclear DNA replication and to be complemented by active and inactive human X chromosomes in human-ts A1S9 somatic cell hybrids...
  88. Zenke Kawasaki Y, Dohi Y, Katoh Y, Ikura T, Ikura M, Asahara T, et al. Heme induces ubiquitination and degradation of the transcription factor Bach1. Mol Cell Biol. 2007;27:6962-71 pubmed
    ..These results suggest that heme within a cell regulates the polyubiquitination and degradation of Bach1. ..
  89. Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M. Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5. J Biol Chem. 1996;271:2795-800 pubmed
    ..In addition, UbcH5 but not UbcH6 or UbcH7 efficiently interacts with the heet protein RSP5. These results indicate that E6-AP can interact with at least two species of E2 and that different hect proteins may interact with different E2s. ..
  90. Saito Y, Doi K, Yamagishi N, Ishihara K, Hatayama T. Screening of Hsp105alpha-binding proteins using yeast and bacterial two-hybrid systems. Biochem Biophys Res Commun. 2004;314:396-402 pubmed
    ..The interaction was validated by the results of a pull-down assay and indirect immunofluorescence analysis. The significance of Hsp105alpha and Hsp105alpha-binding proteins in cells was discussed. ..
  91. Kitahara R. High-Pressure NMR Spectroscopy Reveals Functional Sub-states of Ubiquitin and Ubiquitin-Like Proteins. Subcell Biochem. 2015;72:199-214 pubmed publisher
    ..The recognition of E1 by ubiquitin is best explained by conformational selection rather than by induced-fit motion. ..
  92. Zhang Y, Huang X, Zhao X, Hu Y, Sun H, Kong W. Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence. ORL J Otorhinolaryngol Relat Spec. 2017;79:153-163 pubmed publisher
    ..We also found that overexpression of UCHL1 increased the UPS-related proteins UBE1, PSMA7, ubiquitinated proteins, and monoubiquitin, and proteasomal activity...