GNA13

What is GNA13 protein?

GNA13 gene (G protein subunit alpha 13) is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q24. The GNA13 protein contains several conserved domains, such as the G-α domain, which is involved in the regulation of G protein activity. GNA13 is expressed in both cytoplasm and nucleus and is associated with a variety of cellular processes, including Rho protein signaling, branching of blood vessel morphogenesis, and platelet activation. The GNA13 protein is consisted of 377 amino acids and GNA13 molecular weight is approximately 44.1 kDa.

What is the function of GNA13 protein?

The GNA13 protein is a G-protein alpha subunit that is involved in cell signaling, particularly in the G-protein-coupled receptors (GPCRs) mediated signaling pathway. It plays a role in regulating key biological processes such as cell proliferation, migration, invasion and angiogenesis. In cancer, the function of GNA13 may depend on the specific cellular environment, and it can act as an oncogene that promotes tumor progression or as a tumor suppressor gene that inhibits tumor growth. In addition, the activity and function of GNA13 may be regulated by its post-translational modifications, such as palmitoylation, which affect its stability, subcellular localization, and function in cells. In some cancer types, such as breast and colorectal cancer, GNA13 expression and activity are strongly associated with tumor aggressiveness and prognosis.

GNA13 related signaling pathway

GNA13 protein-related signaling pathways involve its function as a G protein alpha subunit, regulating a variety of intracellular signaling pathways by binding to G protein β/γ subunit complexes and responding to the activation of G protein-coupled receptors (GPCRs). GNA13 promotes cytoskeletal rearrangement and cell migration primarily by activating Rho family small G proteins, such as RhoA. In addition, GNA13 is involved in signaling pathways including phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and nuclear factor κB (NF-κB), which play a key role in cell proliferation, survival, inflammatory response, and tumor development. In some cancers, GNA13 activation is associated with increased aggressiveness and metastatic ability of tumor cells, while in other cases, such as diffuse large B-cell lymphoma, inactivated mutations in GNA13 may lead to loss of tumor suppressor function, which in turn promotes tumor occurrence and development.

Fig1. Gα13-mediated signaling pathway in germinal center (GC) cells and diffuse large B-cell lymphoma (DLBCL) cells. (Viktoriya Syrovatkina, 2019)

GNA13 related diseases

GNA13 protein has been implicated in many diseases, especially in malignant tumors. It plays an important role in regulating cell morphology, contraction, migration and differentiation. In a variety of cancers, GNA13 can regulate the proliferation, invasion and metastasis of cancer cells, showing potential carcinogenic effects. For example, in breast, colorectal, hepatocellular, ovarian, and lung cancers, GNA13 expression levels are strongly associated with tumor aggressiveness and prognosis. In addition, GNA13 may also be involved in the development of placental implantable diseases, and its expression in placental implantable diseases is associated with enhanced invasion and migration of trophoblast cells.

Bioapplications of GNA13

Recombinant human GNA13 protein (rhGNA13) has wide application prospect in biomedical field. As part of the G protein alpha subunit, rhGNA13 plays an important role in the study of fundamental biological processes such as cell signaling, cell proliferation, migration, and differentiation. In drug development, rhGNA13 can be used as a research tool to screen and test drugs that may affect G protein signaling pathways, which is critical for developing therapies to treat cancer and other GNA13-related diseases. In addition, rhGNA13 can also be used to study its role in tumorigenesis, development, and explore its potential function in placental implantable diseases, thereby providing new strategies for the early diagnosis and treatment of these diseases. With a better understanding of GNA13's role in different diseases, the biological applications of rhGNA13 may be further expanded into precision medicine and personalized therapy.

Case Study 1: Sharmin Hasan, 2023

Gα13, a G protein from the G12/13 family, can drive cancer growth through overexpression of its wildtype form, a distinct mechanism from other G proteins. This research indicates that Gα13 activates SRF in HEK293 cells, and its overexpression causes it to move from membranes to the cytoplasm, an effect countered by additional G protein subunits. Moreover, palmitoylation is crucial for Gα13's SRF signaling, a requirement not seen with other modifications in the wildtype protein.

Fig1. Sensitivity of wildtype Gα13 signalling to Rho inhibition.

Fig2. Cytoplasmic localization of overexpressed Gα13.

Case Study 2: Suhail Ahmed Kabeer Rasheed, 2018

Solid tumor treatment often fails because certain cancer-initiating cells with TIC traits survive. GPCRs, which often use GNA13 as a G protein, are linked to cancer growth and TIC traits. This research shows that higher GNA13 levels in various solid tumors correlate with patient survival and metastasis. In HNSCC cells, GNA13 promotes drug resistance and TIC-like features, but inhibiting GNA13 or its key pathways with small molecules can overcome these effects, making cancer cells more susceptible to standard treatments.

Fig3. Blocking GNA13 in GNA13-high cells abrogates TIC markers while overexpression in GNA13-low cells induces them.

Fig4. GNA13 induces NFκB and JNK/MAPK/AP-1 signaling pathways.

GNA13 has several biochemical functions, for example, D5 dopamine receptor binding,G-protein beta/gamma-subunit complex binding,GTP binding. Some of the functions are cooperated with other proteins, some of the functions could acted by GNA13 itself. We selected most functions GNA13 had, and list some proteins which have the same functions with GNA13. You can find most of the proteins on our site.

GNA13 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 GNA13 here. Most of them are supplied by our site. Hope this information will be useful for your research of GNA13.

ARHGEF1;b4dyc6_human;F2R;CXCR5;CXCR4;q96be0_human