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Literature summary extracted from

  • Liu, X.; Sun, L.; Gursel, D.B.; Cheng, C.; Huang, S.; Rademaker, A.W.; Khan, S.A.; Yin, J.; Kiyokawa, H.
    The non-canonical ubiquitin activating enzyme UBA6 suppresses epithelial-mesenchymal transition of mammary epithelial cells (2017), Oncotarget, 8, 87480-87493 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
6.2.1.45 additional information MCF-10A cells stably expressing anti-UBA6 shRNA form similar structures as the wild-type cells, but also develop a number (about 5%) of tumor-like gigantic aggregates, approximately 30% of acini formed in the shUBA6 culture do not exhibit hollow lumen. UBA6 knockout cell phenotype, overview Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.2.1.45 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.2.1.45 ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine Homo sapiens
-
 AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.2.1.45 Homo sapiens A0AVT1
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.2.1.45 epithelial cell
-
 Homo sapiens
-
6.2.1.45 MCF-10A cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.2.1.45 ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
-
 Homo sapiens AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
 ?
6.2.1.45 additional information CDC42 is a substrate of UBA6-initiated ubiquitination Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.2.1.45 non-canonical ubiquitin activating enzyme
-
 Homo sapiens
6.2.1.45 UB activating enzyme
-
 Homo sapiens
6.2.1.45 Uba6
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
6.2.1.45 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
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 Homo sapiens
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 Homo sapiens