GPS2 Antibodies

Background

The G protein pathway inhibitory factor 2 encoded by the GPS2 gene is a key nuclear protein involved in multiple cellular regulatory processes. This protein, as an important component of the transcriptional regulatory complex, participates in biological processes such as fat production, stress response, and inflammation regulation by regulating gene expression. GPS2 interacts with various transcription factors through its N-terminal helical domain, while its C-terminal domain mediates binding to the histone deacetylase complex, thereby achieving epigenetic regulation of target genes. It was first cloned and identified by the team of Spanish scientist Ángel R. Nebreda in 1996 when studying the G protein signaling pathway. Initially, GPS2 was found to be a negative regulatory factor of the G protein signaling pathway. Subsequent studies revealed its extensive functions within the cell nucleus. Its multifunctional molecular structure makes it an important bridge connecting cytoplasmic signal transduction and nuclear transcriptional regulation, providing an important molecular basis for our understanding of the integration mechanism of the cell signal network and the occurrence and development of metabolic diseases.

Structure Function Application Advantage Our Products

Structure of GPS2

GPS2 is a nuclear protein with a molecular weight of approximately 36 kDa. There are slight differences in molecular weight and structure among different species. The table below summarizes the key characteristics of GPS2 in various species:

Species	Human	Mouse	Rat	Chicken
Molecular Weight (kDa)	36.5	36.3	36.4	35.8
Primary Structural Differences	Containing a conserved N-terminal helical domain and a C-terminal zinc finger motif	The homology with human is up to 98%, and the functional domain is completely conserved	Very similar to mice	The sequence is relatively conserved, but there is variation in the C-terminal regulatory region

This protein is composed of approximately 327 amino acids. Its core structure includes a coiled-coil domain located at the N-terminal end, which is responsible for interacting with various transcription factors; the C-terminal part contains a conserved zinc finger domain that mediates binding to the histone deacetylase complex. GPS2 recognizes specific chromatin regions through its zinc finger structure and recruits transcriptional regulatory complexes through the coiled-coil structure, achieving precise epigenetic regulation of target genes. An intramolecular hydrophobic core is formed within the protein to maintain structural stability, and its unique domain organization enables it to act as an adaptor molecule, connecting cellular signals with the nuclear transcriptional regulatory network.

Fig. 1 A schematic presentation of full-length GPS2 and their mutants and their interaction with NS5A.¹

Key structural properties of GPS2:

The N-terminal coiled-coil domain mediates protein interactions
The C-terminal zinc finger domain recognizes specific DNA or chromatin regions
The nuclear localization signal guides the protein to enter the cell nucleus
The hydrophobic core maintains the stability of the three-dimensional conformation
The phosphorylation sites regulate its transcriptional activity and protein stability
The conserved interface that binds to the histone deacetylase complex

Functions of GPS2

The main function of the GPS2 gene is to regulate gene transcription within the cell nucleus and is involved in various physiological processes, such as fat metabolism, stress response, and inflammation regulation.

Function	Description
Transcriptional co-inhibition	As a component of nuclear receptor co-inhibitors, GPS2 inhibits target gene transcription by recruiting histone deacetylase complexes.
Regulation of adipogenesis	Regulates the expression of key genes during adipocyte differentiation, influencing the formation and function of adipose tissue.
Regulation of inflammatory signals	Negatively regulates inflammatory responses by inhibiting the activity of inflammatory-related transcription factors such as NF-κB.
Stress response	Participates in the cellular response mechanisms to oxidative stress and DNA damage, maintaining cellular homeostasis.
Integration of signaling pathways	As a connecting molecule, it links the cytoplasmic signal transduction with the nuclear transcriptional regulatory network.

The function of GPS2 in the transcriptional regulatory network is environment-dependent. Its activity as a co-repressor or co-activator depends on the cell type, signaling environment, and interacting protein partners. This regulatory flexibility makes it a key molecular switch for maintaining cellular metabolic balance and responding to environmental changes.

Applications of GPS2 and GPS2 Antibody in Literature

1. Capaci, Valeria, et al. "Inherited Thrombocytopenia Related Genes: GPS2 Mediates the Interplay Between ANKRD26 and ETV6." Cells 14.1 (2024): 23. https://doi.org/10.3390/cells14010023

The study found that ANKRD26 binds to ETV6 through GPS2 and retains it in the cytoplasm, interfering with the transcriptional inhibitory function of ETV6. This mechanism reveals the common pathogenic pathway of the three thrombocytopenias (ANKRD26-RT, FPD/AML, and ETV6-RT), providing a new perspective for exploring the susceptibility mechanism of myeloid tumors.

2. Hu, Ting, et al. "GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis." Respiratory Research 25.1 (2024): 210. https://doi.org/10.1186/s12931-024-02831-0

The study found that smoking leads to low expression of GPS2 in the pulmonary artery, and its overexpression can improve pulmonary vascular remodeling and pulmonary hypertension. Mechanistically, GPS2 inhibits the Ras/Raf/ERK signaling pathway, thereby reducing the proliferation and migration of smooth muscle cells. This suggests that GPS2 may be a new therapeutic target for COPD-related pulmonary hypertension.

3. Xu, Guodong, Xiu Xin, and Congyi Zheng. "GPS2 is required for the association of NS5A with VAP-A and hepatitis C virus replication." PLoS One 8.11 (2013): e78195. https://doi.org/10.1371/journal.pone.0078195

The study found that GPS2 interacts with the NS5A protein of the hepatitis C virus. Its helical domain binds to domain I of NS5A. As a bridge, GPS2 enhances the binding of NS5A to the host factor VAP-A, promoting viral replication. Silencing GPS2 can inhibit HCV replication, suggesting that it may be a new target for antiviral treatment.

4. Huang, Zhiqiang, et al. "Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4." Nucleic Acids Research 51.3 (2023): 1067-1086. https://doi.org/10.1093/nar/gkac1230

The study found that as a subunit of the HDAC3 co-repressor complex, GPS2 inhibits IL4-induced macrophage alternative activation by antagonizing the activation of enhancers by KDM1A. This mechanism reveals the role of epigenetic regulation in inflammatory responses and provides new ideas for the treatment of metabolic diseases.

5. Liang, Ning, et al. "Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα." Nature communications 10.1 (2019): 1684. https://doi.org/10.1038/s41467-019-09524-z

The study found that the liver protein GPS2 regulates lipid metabolism by interacting with PPARα. Knockout of GPS2 can alleviate fatty liver and fibrosis. The expression of GPS2 is positively correlated with the genetic characteristics of NASH/fibrosis, suggesting that the GPS2-PPARα axis may be a potential therapeutic target for the progression of NAFLD to NASH.

Creative Biolabs: GPS2 Antibodies for Research

Creative Biolabs specializes in the production of high-quality GPS2 antibodies for research and industrial applications. Our portfolio includes monoclonal and polyclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom GPS2 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our GPS2 antibodies, custom preparations, or technical support, contact us at email.

Reference

Xu, Guodong, Xiu Xin, and Congyi Zheng. "GPS2 is required for the association of NS5A with VAP-A and hepatitis C virus replication." PLoS One 8.11 (2013): e78195. Distributed under Open Access license CC BY 4.0, and cropped from the original figure. https://doi.org/10.1371/journal.pone.0078195