UBE2G1

What is UBE2G1 protein?

UBE2G1 (ubiquitin conjugating enzyme E2 G1) gene is a protein coding gene which situated on the short arm of chromosome 17 at locus 17p13. UBE2G1 (UBC7) or ubiquitin-conjugating enzyme E2G 1 is a member of the E2 ubiquitin-conjugating enzyme family and catalyzes the covalent attachment of ubiquitin to other proteins which are involved in degradation of muscle-specific proteins. UBC7 is highly expressed in skeletal muscle. UBC7 is involved in the selective ubiquitylation of different substrates by the same E3 complex. The UBE2G1 protein is consisted of 170 amino acids and its molecular mass is approximately 19.5 kDa.

What is the function of UBE2G1 protein?

The UBE2G1 protein is a key E2 ubiquitin-conjugating enzyme that plays an important role in protein degradation within cells. It works with the ubiquitin-activating enzyme (E1 enzyme) to transfer ubiquitin molecules to target proteins, labeling them for degradation. The function of UBE2G1 is not limited to protein degradation, but also involves cell cycle regulation, DNA repair, signal transduction and immune response. By ubiquitinating different substrates, UBE2G1 helps maintain a stable internal cell environment and normal physiological function.

Fig1. SCF-catalyzed substrate ubiquitylation is extensively buffered at the initiation and elongation steps in human cells compared to the simper yeast SCF system. (Spencer Hill, 2019)

UBE2G1 Related Signaling Pathway

UBE2G1 protein is mainly involved in the signaling pathway of the ubiquitin-proteasome system. In the process of protein degradation, ubiquitination involves three types of enzymes: ubiquitin-activating enzyme (E1), ubiquitin-binding enzyme (E2), and ubiquitin-protein ligase (E3). UBE2G1, as a member of the E2 enzyme class, is responsible for accepting ubiquitin from the E1 complex and covalently attaching it to the target protein. This process may be especially important for marking the degradation of specific proteins in muscles. Through the degradation pathway of the ubiquitin-proteasome system, cells are able to regulate a variety of biological processes, including the cell cycle, regulation of gene transcription, and elimination of abnormal or short-lived proteins.

UBE2G1 Related Diseases

UBE2G1 protein is closely associated with a variety of diseases, including breast cancer, prostate cancer, colon cancer, lung cancer, hepatitis B, congenital heart disease and so on. In addition, UBE2G1 protein has been implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Bioapplications of UBE2G1

Since these biological processes are closely related to the development of a variety of diseases, such as cancer, neurodegenerative diseases, and certain genetic diseases, the application of UBE2G1 protein is mainly focused on disease mechanism research and potential drug development.

Case study 1: Gang Lu, 2018

The cereblon modulating agents (CMs) including lenalidomide, pomalidomide and CC-220 repurpose the Cul4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase complex to induce the degradation of specific neomorphic substrates via polyubiquitination in conjunction with E2 ubiquitin-conjugating enzymes, which have until now remained elusive. Here the researchers show that the ubiquitin-conjugating enzymes UBE2G1 and UBE2D3 cooperatively promote the K48-linked polyubiquitination of CRL4CRBN neomorphic substrates via a sequential ubiquitination mechanism. Blockade of UBE2G1 diminishes the ubiquitination and degradation of neomorphic substrates, and consequent antitumor activities elicited by all tested CMs. For example, UBE2G1 inactivation significantly attenuated the degradation of myeloma survival factors IKZF1 and IKZF3 induced by lenalidomide and pomalidomide, hence conferring drug resistance. UBE2G1-deficient myeloma cells, however, remained sensitive to a more potent IKZF1/3 degrader CC-220.

Fig1. Immunoblot analysis of U937_Cas9 parental or UBE2G1-/- cells with or without stable expression of UBE2G1 wild-type or C90S mutant.

Fig2. Cell proliferation of 293T parental and UBE2G1-/- (clone 13) cells with or without ectopic overexpression of UBE2G1 wild-type or C90S mutant.

Case study 2: Jia Peng, 2022

The large yellow croaker (Larimichthys crocea) is one of the most economically valuable mariculture fish in China. Infection of Pseudomonas plecoglossicida can cause an outbreak of "internal organ white-spot disease", which seriously affects the aquaculture of the large yellow croaker. Ubiquitylation is closely related to the post-translation modification of proteins and plays a vital role in many hosts' immune defense pathways, while the E2-binding enzyme is a key factor in ubiquitination.

The previous genome-wide association study found that the ubiquitin-binding enzyme E2G1 (designed LcUbe2g1) was one of the candidate genes related to disease resistance in large yellow croaker. In this study, the researchers analyzed the molecular characteristics, function, and immune mechanism of the LcUbe2g1. The results of the RT-qPCR and immunohistochemistry analysis revealed that its transcription and translation were significantly activated by the infection of P. plecoglossicida in large yellow croaker. Immunocytochemistry experiments verified the co-localization of LcUBE2G1 and the ubiquitin proteins in the head kidney cells of large yellow croaker. Through GST pull-down, we found that LcUBE2G1 interacted with NEDD8 to co-regulate the ubiquitination process.

Fig3. Relative transcript levels of LcUbe2g1 in different tissues.

Fig4. SDS-PAGE analysis of GST pull-down results of recombinant LcUBE2G1 fusion protein.

UBE2G1 has several biochemical functions, for example, ATP binding,ubiquitin conjugating enzyme activity,ubiquitin protein ligase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by UBE2G1 itself. We selected most functions UBE2G1 had, and list some proteins which have the same functions with UBE2G1. You can find most of the proteins on our site.

UBE2G1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with UBE2G1 here. Most of them are supplied by our site. Hope this information will be useful for your research of UBE2G1.

CUL1;RBCK1;Tmed10