GBP5 (Guanylate Binding Protein 5): A Key Regulator of Inflammasome Activation and Host Defense
Explore the GBP5 gene, its protein product, genomic context, expression patterns, and clinical significance in infectious and inflammatory diseases.
Gene Information Card
| Symbol | GBP5 |
|---|---|
| Full Name | Guanylate Binding Protein 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p22.2 |
| NCBI Gene ID | 115362 ncbi.nlm.nih.gov/gene/115362 |
| Ensembl ID | ENSG00000154451 |
| UniProt ID | Q96PP8 |
| OMIM ID | 611467 |
| HGNC ID | 19895 |
| Aliases | GBP-5 |
Description
GBP5 (Guanylate Binding Protein 5) is a member of the dynamin superfamily of large GTPases. It is strongly induced by interferons (IFN) and plays a critical role in the innate immune response. GBP5 is a key regulator of the NLRP3 inflammasome, promoting its activation in response to specific bacterial and viral pathogens. Beyond its role in inflammasome activation, GBP5 also exhibits antiviral activity against certain viruses, including influenza A virus and encephalomyocarditis virus. Its expression is tightly regulated and its dysregulation has been implicated in various inflammatory and infectious diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Infectious Diseases (e.g., Salmonella, Francisella, Influenza A) | GBP5 is essential for the activation of the NLRP3 inflammasome in response to these pathogens. It promotes the assembly of the inflammasome complex, leading to the cleavage and activation of caspase-1 and the subsequent maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18. | Experimental evidence from in vitro and in vivo mouse models demonstrates that GBP5 knockout cells and mice have impaired NLRP3 inflammasome activation and reduced cytokine production upon infection with these pathogens. |
| Inflammatory Diseases (e.g., Atherosclerosis, Gout) | GBP5-mediated NLRP3 inflammasome activation contributes to the inflammatory response in these conditions. In atherosclerosis, GBP5 expression is upregulated in atherosclerotic plaques and promotes the release of IL-1β, contributing to plaque progression. In gout, monosodium urate (MSU) crystals activate the NLRP3 inflammasome in a GBP5-dependent manner. | Clinical studies show elevated GBP5 expression in atherosclerotic plaques compared to healthy arteries. In vitro studies demonstrate that MSU crystal-induced IL-1β secretion is reduced in GBP5-deficient macrophages. |
| Cancer (e.g., Colorectal Cancer) | The role of GBP5 in cancer is complex and context-dependent. It may influence tumor immunity by modulating the inflammatory microenvironment. Some studies suggest a tumor-suppressive role through its involvement in immune surveillance, while others indicate a pro-tumorigenic role via chronic inflammation. | Expression data from cancer databases (e.g., TCGA) and clinical studies show altered GBP5 expression in various tumors. Functional studies in cell lines and animal models are ongoing to clarify its precise role. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 16.2 | Medium |
| Spleen | 12.8 | Medium |
| Lung | 10.5 | Medium |
| Bone Marrow | 8.9 | Low |
| Liver | 4.3 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (Monocyte) | 25.4 | High baseline expression; further induced by IFN-γ and LPS. |
| HeLa (Cervical Cancer) | 3.1 | Low baseline expression; inducible by IFN-γ. |
| A549 (Lung Cancer) | 8.7 | Moderate baseline expression; inducible by IFN-γ and viral infection. |
| HUVEC (Endothelial) | 2.5 | Low baseline expression; inducible by inflammatory cytokines. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs14304 (c.900A>G, p.Pro300Pro) | Synonymous SNP | Allele frequency varies by population (e.g., ~30% in East Asians, ~10% in Europeans) | No known functional effect; used as a genetic marker in association studies. |
| rs56083757 (c.1123C>T, p.Arg375Trp) | Missense SNP | Rare (MAF < 0.01) | Predicted to be damaging by in silico tools (e.g., SIFT, PolyPhen). Functional studies are limited, but it may affect protein stability or GTPase activity. |
| Somatic mutations in cancer | Various (missense, frameshift, etc.) | Low frequency (< 1%) in various cancers (e.g., colorectal, lung) | Functional impact is largely unknown. Some mutations may alter protein function and contribute to tumor progression or immune evasion, but this requires further investigation. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GBP5 are not well-documented in human populations. However, experimental knockdown or knockout of GBP5 in cell lines and mice leads to impaired NLRP3 inflammasome activation and reduced host defense against specific pathogens, indicating that loss of GBP5 function compromises innate immunity.
Gain of Function (GOF)
Gain-of-function mutations in GBP5 have not been clearly identified. However, overexpression of GBP5 has been shown to enhance NLRP3 inflammasome activation, suggesting that increased GBP5 expression or activity could lead to hyper-inflammatory states.
Dominant Negative (DN)
No dominant-negative mutations have been reported for GBP5. Given its function as a multimeric protein, it is theoretically possible that certain mutations could exert a dominant-negative effect by disrupting complex formation, but this has not been experimentally demonstrated.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GTPase activity |
| • Protein homodimerization activity | • Innate immune response |
| • Inflammasome complex assembly | • Regulation of inflammatory response |
| • Cellular response to interferon-gamma | • Cellular response to lipopolysaccharide |
| • Defense response to virus | • Cytokine production |
Pathways
• NLRP3 Inflammasome Pathway
• Interferon-gamma Signaling Pathway
• Innate Immune System
• Cytokine Signaling in Immune system
Protein Summary
The GBP5 protein is a 586-amino acid large GTPase belonging to the guanylate-binding protein (GBP) family. It consists of a large N-terminal GTPase domain, a middle helical domain, and a C-terminal domain containing a CaaX motif for isoprenylation, which is crucial for its membrane association. GBP5 is primarily cytosolic but can associate with membranes upon activation. It functions as a homodimer and exhibits GTPase activity, hydrolyzing GTP to GDP. Its key role is in the activation of the NLRP3 inflammasome. Upon detection of specific pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs), GBP5 interacts with NLRP3, promoting its oligomerization and the assembly of the inflammasome complex. This leads to the activation of caspase-1, which cleaves pro-IL-1β and pro-IL-18 into their mature, secreted forms. GBP5 also has direct antiviral activity against certain viruses by interfering with viral entry or replication.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GBP5 Knockout HEK293 Cell Line | EDJ-KQ7520 | Human | 115362 | Details Get a Quote |
| GBP5 Knockout HeLa Cell Line | EDJ-KQ57953 | Human | 115362 | Details Get a Quote |
| GBP5 Knockout A-549 Cell Line | EDJ-KQ66444 | Human | 115362 | Details Get a Quote |
| GBP5 Knockout HCT 116 Cell Line | EDJ-KQ74866 | Human | 115362 | Details Get a Quote |
