Scientific Background: UBA3 (also known as UBE1C) or ubiquitin-like modifier activating enzyme 3 is a member of the E1 ubiquitin-activating enzyme family. UBA3 associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. The mechanism of NEDD8 activation by APPBP1-UBA3 shows a high degree of conservation with ubiquitin activation by UBA1 (1). The NEDD8-activating enzyme, or NAE, composed of NAE1 and UBA3 subunits, is an essential component for the treatment of cancer disease (2).
2. Soucy, T. A. et.al: An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458: 732-736, 2009.
NCBI and Uniprot Product Information
NCBI Description
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Uniprot Description
Function: Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression. Ref.6 Ref.7 Ref.8
Enzyme regulation: Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.
Pathway: Protein modification; protein neddylation.
Subunit structure: Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand
By similarity. Interacts with TBATA
By similarity. Ref.8
Tissue specificity: Ubiquitously expressed. Ref.6
Miscellaneous: Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex.
Sequence similarities: Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.
Sequence caution: The sequence AAC27648.1 differs from that shown. Reason: Erroneous initiation.
Research Articles on UBA3 (UBE1C)
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Product Notes
The UBA3 (UBE1C) uba3 (Catalog #AAA515314) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant full-length human UBA3 (UBE1C) was expressed by baculovirus in Sf9 insect cells. AAA Biotech's UBA3 (UBE1C) can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the UBA3 (UBE1C) uba3 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "UBA3 (UBE1C), Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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