Genomes and Genes
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
- Takahashi E, Ayusawa D, Kaneda S, Itoh Y, Seno T, Hori T. The human ubiquitin-activating enzyme E1 gene (UBE1) mapped to band Xp11.3----p11.23 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1992;59:268-9 pubmedThe human gene for ubiquitin-activating enzyme E1 (UBE1) was localized by a direct mapping system that combined fluorescence in situ hybridization with replicated R-bands on prometaphase chromosomes...
- Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit R, et al. Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase. J Biol Chem. 2004;279:3916-24 pubmed..Hence, the results indicate that BRCA1-BARD1 mediates novel polyubiquitin chains that may be distinctly edited by 26 S proteasome from conventional Lys-48-linked polyubiquitin chains. ..
- Zhu H, Zhou Z, Huo R, Huang X, Lu L, Lin M, et al. Identification and characteristics of a novel E1 like gene nUBE1L in human testis. Acta Biochim Biophys Sin (Shanghai). 2004;36:227-34 pubmed..In conclusion, nUBE1L is a novel human E1 like gene highly expressed in adult testis, which plays key role in ubiquitin system, and accordingly influences spermatogenesis and male fertility. ..
- 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...
- 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. ..
- 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 pubmedb>UBE1 is known as the human ubiquitin-activating enzyme (E1), which activates ubiquitin in an ATP-dependent manner...
- 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 publisher..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...
- 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..enzyme USE1 which auto-FAT10ylates itself in cis, the tumor suppressor p53 and the ubiquitin-activating enzyme UBE1 (UBA1)...
- 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...
- 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. ..
- 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 publisherUba6 is a homolog of the ubiquitin-activating enzyme, Uba1, and activates two ubiquitin-like proteins (UBLs), ubiquitin and FAT10...
- Liu X, Sun L, Gursel D, Cheng C, Huang S, Rademaker A, et al. The non-canonical ubiquitin activating enzyme UBA6 suppresses epithelial-mesenchymal transition of mammary epithelial cells. Oncotarget. 2017;8:87480-87493 pubmed publisher..The two ubiquitin activating enzymes (E1) in human genome, UBA1 and UBA6, initiate ubiquitination by ATP-dependent activation of ubiquitin...
- Xia T, Dimitropoulou C, Zeng J, Antonova G, Snead C, Venema R, et al. Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase. Am J Physiol Heart Circ Physiol. 2007;293:H3080-7 pubmed..This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function. ..
- Ramser J, Ahearn M, Lenski C, Yariz K, Hellebrand H, von Rhein M, et al. Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy. Am J Hum Genet. 2008;82:188-93 pubmed publisher..3-Xq11.1). This resulted in detection of three rare novel variants in exon 15 of UBE1 that segregate with disease: two missense mutations (c.1617 G-->T, p.Met539Ile; c.1639 A-->G, p...
- He P, Tang Y, Cai W, Huang Y, Fang C, Jing H. [The quantitative analysis of Ub and UbE1 in focus of traumatic epilepsy]. Fa Yi Xue Za Zhi. 2010;26:84-7 pubmed..The expression of mRNA and protein of Ub and UbE1 were detected by RT-PCR and Western blot. Statistical analysis was used to compare the data between three groups...
- Li Y, Xie P, Lu L, Wang J, Diao L, Liu Z, et al. An integrated bioinformatics platform for investigating the human E3 ubiquitin ligase-substrate interaction network. Nat Commun. 2017;8:347 pubmed publisher..Here, the authors take an in silico naïve Bayesian classifier approach to integrate multiple lines of evidence for E3-substrate prediction, enabling prediction of the proteome-wide human E3 ligase interaction network. ..
- Zhou W, Zhu P, Wang J, Pascual G, Ohgi K, Lozach J, et al. Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation. Mol Cell. 2008;29:69-80 pubmed publisher..We suggest that distinct H2A ubiquitinases, each recruited based on interactions with different corepressor complexes, contribute to distinct transcriptional repression programs. ..
- Ungermannova D, Parker S, Nasveschuk C, Wang W, Quade B, Zhang G, et al. Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (e1). PLoS ONE. 2012;7:e29208 pubmed publisher..Thus, Largazole and select analogs are a novel class of ubiquitin E1 inhibitors and valuable tools for studying ubiquitination in vitro. This class of compounds could be further developed and potentially be a useful tool in cells. ..
- Ronchi V, Haas A. Measuring rates of ubiquitin chain formation as a functional readout of ligase activity. Methods Mol Biol. 2012;832:197-218 pubmed publisher..These kinetic methods provide mechanistic insights that are otherwise inaccessible by other experimental approaches and yield a precision in characterizing protein interactions that exceeds that of other techniques. ..
- Liu Z, Chen P, Gao H, Gu Y, Yang J, Peng H, et al. Ubiquitylation of autophagy receptor Optineurin by HACE1 activates selective autophagy for tumor suppression. Cancer Cell. 2014;26:106-20 pubmed publisher..By demonstrating that the HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells, our findings may open an avenue for developing autophagy-targeted therapeutic intervention into cancer. ..
- Tan X, Liang R, Chuang S. hHR23A is required to control the basal turnover of Chk1. Cell Signal. 2015;27:2304-13 pubmed publisher....
- Allen E, Ding J, Wang W, Pramanik S, Chou J, Yau V, et al. Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. Nature. 2005;438:224-8 pubmed..Our results identify gigaxonin as a ubiquitin scaffolding protein that controls MAP1B-LC degradation, and provide insight into the molecular mechanisms underlying human neurodegenerative disorders. ..
- Zacksenhaus E, Sheinin R, Wang H. Localization of the human A1S9 gene complementing the ts A1S9 mouse L-cell defect in DNA replication and cell cycle progression to Xp11.2----p11.4. Cytogenet Cell Genet. 1990;53:20-2 pubmedThe temperature-sensitive ts A1S9 mouse L-cell mutant is defective in an X-linked gene essential for progression of cells through the S phase of the cell division cycle...
- Nagai Y, Kaneda S, Nomura K, Yasuda H, Seno T, Yamao F. Ubiquitin-activating enzyme, E1, is phosphorylated in mammalian cells by the protein kinase Cdc2. J Cell Sci. 1995;108 ( Pt 6):2145-52 pubmed..These findings suggest that E1 is a target of Cdc2 kinase in the cell, implying that the ubiquitin system may be dynamically involved in cell cycle control through phosphorylation of this key enzyme. ..
- Narasimhan J, Potter J, Haas A. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. J Biol Chem. 1996;271:324-30 pubmed..Thus, interferon-responsive cells contain a pathway for UCRP ligation that is parallel but distinct from that of ubiquitin. ..
- Shang F, Deng G, Obin M, Wu C, Gong X, Smith D, et al. Ubiquitin-activating enzyme (E1) isoforms in lens epithelial cells: origin of translation, E2 specificity and cellular localization determined with novel site-specific antibodies. Exp Eye Res. 2001;73:827-36 pubmed..This observation suggests that E1A and E1B ubiquitinate different proteins and serve different functions in intact cells. ..
- Seufert W, McGrath J, Jentsch S. UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin-conjugating enzymes involved in protein degradation. EMBO J. 1990;9:4535-41 pubmed..This specific requirement for UBC1 after a state of quiescence suggests that degradation of certain proteins may be crucial at this transition point in the yeast life cycle. ..
- Pickart C, Kasperek E, Beal R, Kim A. Substrate properties of site-specific mutant ubiquitin protein (G76A) reveal unexpected mechanistic features of ubiquitin-activating enzyme (E1). J Biol Chem. 1994;269:7115-23 pubmed..The intermediacy of ubiquitin adenylate thus provides a previously unrecognized catalytic advantage in the E1 mechanism. ..
- Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, et al. The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem. 2001;276:14537-40 pubmed..These results suggest that the BRCA1-BARD1 complex contains a ubiquitin ligase activity that is important in prevention of breast and ovarian cancer development. ..
- Handley P, Mueckler M, Siegel N, Ciechanover A, Schwartz A. Molecular cloning, sequence, and tissue distribution of the human ubiquitin-activating enzyme E1. Proc Natl Acad Sci U S A. 1991;88:258-62 pubmed..Tissue distribution reveals a single 3.5-kilobase E1 message ubiquitous among tissues and cell lines. ..
- Huen M, Huang J, Yuan J, Yamamoto M, Akira S, Ashley C, et al. Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol Cell Biol. 2008;28:6104-12 pubmed publisher..We propose that the RNF8 RING domain selects and loads a subset of UBC13 molecules, distinct from those that exist as heterodimers, onto sites of double-strand breaks, which facilitates the amplification of DNA damage signals. ..
- Bruce M, Kanelis V, Fouladkou F, Debonneville A, Staub O, Rotin D. Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain. Biochem J. 2008;415:155-63 pubmed publisher..These findings also point to a novel mechanism employed by a ubiquitin ligase to regulate itself differentially compared with substrate ubiquitination and stability. ..
- Trausch J, Grenfell S, Handley Gearhart P, Ciechanover A, Schwartz A. Immunofluorescent localization of the ubiquitin-activating enzyme, E1, to the nucleus and cytoskeleton. Am J Physiol. 1993;264:C93-102 pubmed..The variable distribution of E1 among cell lines, including its apparent cytoskeletal association, suggests pleiotropic functions of this enzyme and the ubiquitin-conjugating system...
- Malakhova O, Zhang D. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response. J Biol Chem. 2008;283:8783-7 pubmed publisher..To our knowledge, this is the first example of a Ub-like protein with the ability to interfere with Ub-E2 and E3 interaction to inhibit protein ubiquitination...
- Schafer A, Kuhn M, Schindelin H. Structure of the ubiquitin-activating enzyme loaded with two ubiquitin molecules. Acta Crystallogr D Biol Crystallogr. 2014;70:1311-20 pubmed publisherThe activation of ubiquitin by the ubiquitin-activating enzyme Uba1 (E1) constitutes the first step in the covalent modification of target proteins with ubiquitin...
- Pauli E, Chan Y, Davis M, Gableske S, Wang M, Feister K, et al. The ubiquitin-specific protease USP15 promotes RIG-I-mediated antiviral signaling by deubiquitylating TRIM25. Sci Signal. 2014;7:ra3 pubmed publisher..Together, these data identify USP15 as a critical regulator of the TRIM25- and RIG-I-mediated antiviral immune response, thereby highlighting the intricate regulation of innate immune signaling. ..
- Xia Y, Pao G, Chen H, Verma I, Hunter T. Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein. J Biol Chem. 2003;278:5255-63 pubmed..We also found that co-expression of BRCA1 and BARD1 in living cells increased the abundance and stability of both proteins and that this depended on their ability to heterodimerize. ..
- Chong R, Wu K, Spratt D, Yang Y, Lee C, Nayak J, et al. Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination. Proc Natl Acad Sci U S A. 2014;111:8434-9 pubmed publisher....
- Choi J, Park B, Chi S, Bae K, Kim S, Cho S, et al. HAX1 regulates E3 ubiquitin ligase activity of cIAPs by promoting their dimerization. Oncotarget. 2014;5:10084-99 pubmed..Taken together, these results unveil a novel role of HAX1 in the non-canonical NF-κB pathway, and provide an important clue that HAX1 is a potential therapeutic target for the treatment of cancer. ..
- Groen E, Gillingwater T. UBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration. Trends Mol Med. 2015;21:622-632 pubmed publisher..Ubiquitin-like modifier activating enzyme 1 (UBA1), the E1 ubiquitin-activating enzyme, sits at the apex of the ubiquitin cascade and represents an important ..
- Turner T, Shao Q, Wang W, Wang Y, Wang C, Kinlock B, et al. Differential Contributions of Ubiquitin-Modified APOBEC3G Lysine Residues to HIV-1 Vif-Induced Degradation. J Mol Biol. 2016;428:3529-39 pubmed publisher....
- Ayusawa D, Kaneda S, Itoh Y, Yasuda H, Murakami Y, Sugasawa K, et al. Complementation by a cloned human ubiquitin-activating enzyme E1 of the S-phase-arrested mouse FM3A cell mutant with thermolabile E1. Cell Struct Funct. 1992;17:113-22 pubmed..Relevance of the unusually high incidence of the temperature-sensitive E1 mutation was discussed in terms of the E1 as a determinant of heat tolerance of cells. ..
- Balak C, Hunter J, Ahearn M, Wiley D, D URSO G, Baumbach Reardon L. Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular Atrophy. F1000Res. 2017;6:1636 pubmed publisher..spinal muscular atrophy (XL-SMA) results from mutations in the Ubiquitin-Like Modifier Activating Enzyme 1 ( UBA1)...
- Darnay B, Reddy S, Aggarwal B. Physical and functional association of a serine-threonine protein kinase to the cytoplasmic domain of the p80 form of the human tumor necrosis factor receptor in human histiocytic lymphoma U-937 cells. J Biol Chem. 1994;269:19687-90 pubmed..This p80 TNF receptor-associated protein and the associated kinase described here are referred to as p80-TRAP and p80-TRAK, respectively. ..
- Tiago A, Nkeh B, Candy G, Badenhorst D, Defterios D, Brooksbank R, et al. Association study of eight candidate genes with renin status in mild-to-moderate hypertension in patients of African ancestry. Cardiovasc J S Afr. 2001;12:75-80 pubmed..However, a potential small role for some loci may exist, and epistasis or genotype-phenotype interactions as well as alternative inheritance models and variants still need to be evaluated. ..
- Kirkpatrick D, Weldon S, Tsaprailis G, Liebler D, Gandolfi A. Proteomic identification of ubiquitinated proteins from human cells expressing His-tagged ubiquitin. Proteomics. 2005;5:2104-11 pubmed..This proteomics method, developed for the analysis of ubiquitinated proteins, is a step towards large-scale characterization of Ub-protein conjugates in numerous physiological and pathological states. ..
- Ohtsubo M, Nishimoto T. The gene coding a ubiquitin-activating enzyme may locate on X chromosome. Biochem Biophys Res Commun. 1988;153:1173-8 pubmed..The ubiquitin-activating enzyme may be required for completion of the S phase. ..
- Leng L, Xu C, Wei C, Zhang J, Liu B, Ma J, et al. A proteomics strategy for the identification of FAT10-modified sites by mass spectrometry. J Proteome Res. 2014;13:268-76 pubmed publisher..These results should be very useful for investigating the biological functions of FAT10. ..
- Nicassio F, Corrado N, Vissers J, Areces L, Bergink S, Marteijn J, et al. Human USP3 is a chromatin modifier required for S phase progression and genome stability. Curr Biol. 2007;17:1972-7 pubmed..Together, our results implicate USP3 as a novel chromatin modifier in the maintenance of genome integrity. ..
- Whitby F, Xia G, Pickart C, Hill C. Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes. J Biol Chem. 1998;273:34983-91 pubmed..One such residue, Ala-72 (Arg in ubiquitin), is shown to perform a key role in selecting against reaction with the ubiquitin E1 enzyme, thereby acting to prevent the inappropriate diversion of NEDD8 into ubiquitin-specific pathways. ..
- . Molecular cloning, sequence, and tissue distribution of the human ubiquitin-activating enzyme E1. Proc Natl Acad Sci U S A. 1991;88:7456 pubmed
- Takeuchi T, Iwahara S, Saeki Y, Sasajima H, Yokosawa H. Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme. J Biochem. 2005;138:711-9 pubmed..Thus, we provide evidence for a link between the ubiquitin conjugation system and the ISG15 conjugation system. ..
- Schwartz A, Trausch J, Ciechanover A, Slot J, Geuze H. Immunoelectron microscopic localization of the ubiquitin-activating enzyme E1 in HepG2 cells. Proc Natl Acad Sci U S A. 1992;89:5542-6 pubmed..The lumen of rough endoplasmic reticulum, Golgi complex, endosomes, and lysosomes were negative. The specific localization of E1 to distinct subcellular organelles suggests that E1 may play multiple physiological roles within the cell. ..
- Goebl M, Yochem J, Jentsch S, McGrath J, Varshavsky A, Byers B. The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science. 1988;241:1331-5 pubmed..The cell cycle function of CDC34 is thus likely to be mediated by the ubiquitin-conjugating activity of its product. ..
- Chou C, Hwang G, Hageman D, Han L, Agrawal P, Pisitkun T, et al. Identification of UT-A1 and AQP2 interacting proteins in rat inner medullary collecting duct. Am J Physiol Cell Physiol. 2017;:ajpcell.00082.2017 pubmed publisher..modifications: phosphorylation (protein kinases Cdc42bpb, Phkb, Camk2d and Mtor), ubiquitylation/deubiquitylation (Uba1, Usp9x), and neddylation (Nae1 and Uba3)...
- Gururaja T, Li W, Noble W, Payan D, Anderson D. Multiple functional categories of proteins identified in an in vitro cellular ubiquitin affinity extract using shotgun peptide sequencing. J Proteome Res. 2003;2:394-404 pubmed..This suggests a link between the ubiquitin system and these cellular processes. This map of cellular ubiquitin-associated proteins may be useful for further studies of ubiquitin system function. ..
- Sadri H, Steinhoff Wagner J, Hammon H, Bruckmaier R, Görs S, Sauerwein H. Mammalian target of rapamycin signaling and ubiquitin proteasome-related gene expression in 3 different skeletal muscles of colostrum- versus formula-fed calves. J Dairy Sci. 2017;100:9428-9441 pubmed publisher..The mRNA abundance of ubiquitin activating enzyme (UBA1) and ubiquitin conjugating enzyme 1 (UBE2G1) enzymes was not affected by diet, whereas that of ubiquitin ..
- Kang D, Chen J, Wong J, Fang G. The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition. J Cell Biol. 2002;156:249-59 pubmed..Thus, the Chfr pathway represents a novel checkpoint pathway that regulates the entry into mitosis by ubiquitin-dependent proteolysis. ..
- Pesiri V, Totta P, Marino M, Acconcia F. Ubiquitin-activating enzyme is necessary for 17β-estradiol-induced breast cancer cell proliferation and migration. IUBMB Life. 2014;66:578-85 pubmed publisher..These discoveries indicate a new molecular circuitry that can be further explored to define new opportunities for BC treatment. ..
- Gallegos J, Litersky J, Lee H, Sun Y, Nakayama K, Nakayama K, et al. SCF TrCP1 activates and ubiquitylates TAp63gamma. J Biol Chem. 2008;283:66-75 pubmed..Therefore, our study reveals that SCF(betaTrCP1) is an E3 ligase that activates p63 through ubiquitylation. ..
- Phillips A, Zhang Y, Cunningham C, Zhou L, Forrest W, Liu P, et al. Conformational dynamics control ubiquitin-deubiquitinase interactions and influence in vivo signaling. Proc Natl Acad Sci U S A. 2013;110:11379-84 pubmed publisher..Taken together, these results show that conformational dynamics are critical for ubiquitin-deubiquitinase interactions and imply that the fine tuning of motion has played a key role in the evolution of ubiquitin as a signaling hub. ..
- Cook J, Chock P. Phosphorylation of ubiquitin-activating enzyme in cultured cells. Proc Natl Acad Sci U S A. 1995;92:3454-7 pubmed..These observations suggest new hypotheses concerning mechanisms of metabolic regulation of the ubiquitin conjugation pathway. ..