Literature summary for 6.2.1.45 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 .

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Protein Variants

Protein Variants	Comment	Organism
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

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	A0AVT1	-	-

Source Tissue

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

Substrates and Products (Substrate)

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

Synonyms

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

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

General Information

General Information	Comment	Organism
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
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

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Release 2023.1 (January 2023)