6.2.1.45	evolution	5 amino acids and 8 bases are different in cDNA and DNA sequences of CrUBE1 between Wuzishatangju and Shatangju, respectively	733931	
6.2.1.45	evolution	MUB inhibition of E1 is conserved between plants and humans	745858	
6.2.1.45	evolution	yeast Ub-activating enzyme E1 is a modular protein, evolved from small prokaryotic proteins, which had specific functions, and in E1 enzyme they form domains that work together as part of a big enzyme	-, 760825	
6.2.1.45	malfunction	a defect in the UBA1 gene results in detrimental effects on cell cycle progression, and deletion of the UBA1 gene is lethal to the organism	-, 760825	
6.2.1.45	malfunction	identification of loss-of-function mutations in the Drosophila ubiquitin activating enzyme, the most upstream enzyme in the ubiquitin pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reach adulthood, but mutants exhibit further reduced lifespan and show inappropriate Ras activation in the brain. Removing just one functional copy of Ras restores the lifespan of heterozygous E1 mutants to that of wild-type flies and increase the survival of homozygous E1 mutants. E1 homozygous mutants also show severe motor impairment involved in early mortality. Phenotypes, detailed overview	735079	
6.2.1.45	malfunction	impaired UBA1 activity in a range of neurodegenerative conditions, including Parkinson's disease, Alzheimer's disease, Huntington's disease and spinal muscular atrophy	766918	
6.2.1.45	malfunction	lethality of RNA antisense silencing of Giardia E1	-, 733043	
6.2.1.45	malfunction	local delivery of potent chemical UBA1 inhibitor PYR-41 and UBA1 shRNA lentivirus both result in a substantial decrease in intimal hyperplasia at 2 weeks and 4 weeks after balloon injury. UBA1 inhibition also reduces Ki-67 positive cell percentage and inflammatory response in the carotid artery wall. In vitro UBA1 inhibition is able to ameliorate TNF-alpha-induced nuclear factor-kappa B (NF-kappaB) activation by reducing IkappaB degradation in vascular smooth muscle cells (VSMCs). UBA1 inhibition also leads to the accumulation of short-lived proteins such as p53, p21 and c-jun, which may account for the UBA1 inhibition-induced cell cycle delay. Thus, VSMCs proliferation is blocked. UBA1 inhibition effectively suppresses neointimal thickening through its anti-proliferative and anti-inflammatory effects	744190	
6.2.1.45	malfunction	mammary epithelial MCF-10A cells expressing shRNA against UBA6 fail in establishing cell cycle arrest in response to detachment from extracellular matrix, confluency with fully engaged cell-cell contact or growth factor deprivation. Moreover, UBA6-deficient MCF-10A cells undergo spontaneous epithelial-mesenchymal transition (EMT) under growth factor deprivation and exhibit accelerated kinetics of TGF-beta-induced EMT. UBA6 knockdown perturbs acinar morphogenesis and leads to formation of gigantic cell aggregates in mammary epithelial 3-D culture. UBA6 depletion suppresses contact innhibition of the cell cycle. UBA6 downregulation promotes cancer progression such as EMT and invasion in a population of human breast cancers	745952	
6.2.1.45	malfunction	the LMO2 protein interacts with the E1 ubiquitin-activating enzyme UBA6 at the C-terminal ubiquitin fold domain (UFD), which mediates the recognition and recruitment of the E2-conjugating enzyme USE1. Functionally, the LMO2-UBA6 interaction disturbes the interaction between UBA6 and USE1 and leads to the decline of the overall cellular FAT10ylation level as well as the FAT10ylation and degradation of a known FAT10 substrate p62	744237	
6.2.1.45	metabolism	early pregnancy influences expression of STAT1, Mx1, IP-10 and UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep	760342	
6.2.1.45	metabolism	the ubiquitin E1 activating enzyme ubiquitin-activating enzyme 1 (UBE1) is a putative substrate of FAT10. The ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) directly targets its substrates for proteasomal degradation by becoming covalently attached via its C-terminal diglycine motif to internal lysine residues of its substrate proteins. UBE1 and FAT10 formed a stable isopeptide linkage. The conjugation machinery consists of the bispecific E1 activating enzyme ubiquitin-like modifier activating enzyme 6 (UBA6), the likewise bispecific E2 conjugating enzyme UBA6-specific E2 enzyme 1 (USE1), and possibly E3 ligases, overview. UBE1 and FAT10 form a stable non-reducible conjugate, FAT10ylation of UBE1 depends on the diglycine motif of FAT10	735013	
6.2.1.45	metabolism	the ubiquitin-activating enzyme E1 (UBA1, E1) is the apex of the ubiquitin proteasome pathway	744190	
6.2.1.45	metabolism	ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin	-, 760825	
6.2.1.45	metabolism	ubiquitin-activating enzyme E1 catalyzes the first step in the ubiquitination reaction, which targets a protein for degradation via a proteasome pathway. The enzyme plays an important role in metabolic processes	733931	
6.2.1.45	metabolism	ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy	766918	
6.2.1.45	additional information	conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation. UBE1 uses Cys632 in the active site	735013	
6.2.1.45	additional information	sequence and structure comparisons, overview	733532	
6.2.1.45	additional information	the enzyme has six ATP binding sites, one catalytic residue, and one E2 binding domain	733931	
6.2.1.45	additional information	UBA5 is the smallest and structurally simplest E1. The active site Cys of UBA5 (Cys 250) is located within the adenylation domain, but this domain is not sufficient for the formation of a thioester bond between the UFM1 C terminus and the UBA5 catalytic Cys. Modeling of a cis-binding mechanism of UFM1 to UBA5. Trans-binding mechanism of UFM1 transfer to the E2, UFC1. Homodimerization of UBA5 is essential for activating UFM1	744655	
6.2.1.45	physiological function	a lysine 48-linked polyubiquitin chain, assembled upon an internal lysine residue of a substrate protein, becomes the principle signal for recognition and target degradation by the 26S proteasome. E1 is not only essential for the initial ATP-dependent activation of ubiquitin in the ubiquitin degradtion pathway, but also capable of the catalytic extension of the polyubiquitin chain on a mono-ubiquitinated substrate	725376	
6.2.1.45	physiological function	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. Overexpression of the enzyme UBE1 enhances the replication of the virus, and knockdown of UBE1 decreases virus replication. te virus manipulates UBE1 for increased viral replication, and the SAP domain is involved in this process, overview	734563	
6.2.1.45	physiological function	early pregnancy reduces expression of UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep	760342	
6.2.1.45	physiological function	enzyme E1 is an essential gene for parasite viability and is implicated in encystation.Enzyme overexpression greatly increases the encystation rate, indicating a relationship between E1 and Giardia differentiation	-, 733043	
6.2.1.45	physiological function	in mouse embryo fibroblast cell A31N-ts20, which is thermosensitive for ubiquitin-activating enzyme E1, the enzymatic activity of the enzyme is heat-inactivatable in vitro; and a major mechanism responsible for E1 inactivation in vivo consists of accelerated destruction. In vivo, ubiquitination of the various protein substrates in A31N-ts20 cells requires different amounts of E1 enzyme	727412	
6.2.1.45	physiological function	isoform Uba6 forms a covalent link with ubiquitin in vitro and in vivo, which is sensitive to reducing conditions. In an in vitro polyubiquitylation assay, recombinant Uba6 can activate ubiquitin and transfer it onto the ubiquitin-conjugating enzyme UbcH5B. Ubiquitin activated by Uba6 can be used for ubiquitylation of p53 by MDM2 and supports the autoubiquitylation of the E3 ubiquitin ligases HectH9 and E6-AP	674842	
6.2.1.45	physiological function	knockdown of E1 decreases the abundance of ubiquitinated proteins in leukemia and myeloma cells and induces cell death. Inhibitor 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione, i.e. PYZD-4409, induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells. Mechanistically, genetic or chemical inhibition of E1 increases expression of E1 stress markers. ER membrane protein BI-1 overexpression blocks cell death after E1 inhibition	707854	
6.2.1.45	physiological function	plays an important role in the first step of the proteasome pathway to activate ubiquitin. The UBE1 is a two-step intramolecular and ATP-dependent reaction to generate a high-energy E1-thiol-ester-ubiquitin intermediate. The activated ubiquitin are then transferred to ubiquitin-conjugating enzyme E2	709881	
6.2.1.45	physiological function	protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Ezrin and CUGBP1 undergo Uba6-dependent polyubiquitination. Uba1 is not required, in contrast to Uba6, for polyubiquitination and proteasomal degradation of ezrin and CUGBP1. Distinctive substrate pools exist for Uba1 and Uba6 that reflect non-redundant biological roles for Uba6	745863	
6.2.1.45	physiological function	protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Polyubiquitination and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1. Ezrin and CUGBP1 undergo Uba6-dependent polyubiquitination. Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. Distinctive substrate pools exist for Uba1 and Uba6 that reflect non-redundant biological roles for Uba6	745863	
6.2.1.45	physiological function	the enzyme (Uba6) initiates signal transduction by activating ubiquitin and the ubiquitin-like protein FAT10 in a two-step process involving sequential catalysis of adenylation and thioester bond formation	767593	
6.2.1.45	physiological function	the enzyme regulates the ubiquitin conjugation cascade	766440	
6.2.1.45	physiological function	the ubiquitin-activating enzyme E1 (UBA1) plays a critical role in protein degradation and in pathological processes. UBA1 participates the development of vascular restenosis	744190	
6.2.1.45	physiological function	UBA1 is essential for autophagy in certain cell types	766918	
6.2.1.45	physiological function	UBA6 is the specific E1 that activates FAT10 and USE1 (also known as UBE2Z), an E2-conjugating enzyme that interacts exclusively with UBA6, accepts both ubiquitin and FAT10 from UBA6. UBA6 is one of the eight known E1 ubiquitin-activating enzymes and is the only E1 enzyme that can activate both ubiquitin and ubiquitin-like protein HLA-F adjacent transcript 10 (FAT10). In eukaryotic cells, the post-translational modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is the most common trigger for protein degradation and is involved in the regulation of a wide range of biological processes. FAT10 (HLA-F-adjacent transcript 10), which belongs to the UBL family, is activated specifically through the UBA6-USE1 cascade and targets substrates covalently for 26S proteasomal degradation. The E1 ubiquitin-activating enzyme interacts with LMO2, a well-recognized transcriptional regulator in hematopoietic and endothelial systems, that is involved in the regulatory hierarchy of UBA6-USE1-FAT10ylation pathway by targeting the E1 enzyme UBA6	744237	
6.2.1.45	physiological function	UBE1s catalyze the first steps in the ubiquitin conjugation cascade and are potentially involved in compatible pollination and ubiquitinmediated S-RNase degradation	733931	
6.2.1.45	physiological function	ubiquitin-activating enzyme (E1) activates ubiquitin (Ub) conjugating enzyme (E2)	745858	
6.2.1.45	physiological function	ubiquitin-activating enzyme (E1) is a key regulator in protein ubiquitination, which lies on the upstream of the ubiquitin-related pathways and determines the activation of the downstream enzyme cascade	733532	
6.2.1.45	physiological function	ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin. E1 along with other enzymes plays a role in the regulation of cell cycle proteins like histone H2A and p53, which are essential for cell cycling	-, 760825	
6.2.1.45	physiological function	ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin. The SCCH domain and to some extent the ubiquitin fold domain (UFD) apparently interfere with cellular functions such as survival under various stresses	-, 760825	
6.2.1.45	physiological function	ubiquitin-activating enzyme 1 does not act as a second E1 activating enzyme for ubiquitin-like modifier HLA-F adjacent transcript but FAT10ylation of UBE1 leads to its proteasomal degradation	735013	
6.2.1.45	physiological function	ubiquitination is the process of covalent conjugation of ubiquitin (UB) to cellular proteins mediated by E1 (UB activating enzyme)-E2 (UB conjugating enzyme)-E3 (UB ligase) enzyme cascade. Ubiquitination plays critical roles in various diseases including cancer. E1 catalyzes the formation of the thioester bond between the C-terminus of UB and the active site cysteine of E1 in presence of ATP, initiating UB transfer to E2 and subsequently to target proteins that are recruited by E3. The non-canonical ubiquitin activating enzyme UBA6 suppresses epithelial-mesenchymal transition of mammary epithelial cells. Ubiquitination pathways initiated specifically by UBA6 set a suppressive barrier against critical steps of mammary carcinogenesis such as loss of polarity, anoikis resistance and epithelial-mesenchymal transition (EMT). The Rho-GTPase CDC42 is one of the specific targets of UBA6-initiated ubiquitination and plays a key role in the function of UBA6 in controlling epithelial homeostasis, since a CDC42 inhibitor, ML141, rescues UBA6-deficient cells from the EMT phenotype. UBA6 is low or undetectable in a substantial population of invasive breast cancer tissues, suggesting the cancer-associated roles for the non-canonical E1	745952