GBP1 (Guanylate Binding Protein 1): A Key Interferon-Induced GTPase in Immunity and Inflammation
Explore the GBP1 gene, its protein product, genomic context, expression patterns, associated diseases, and functional roles in immune defense and inflammatory pathways.
Gene Information Card
| Symbol | GBP1 |
|---|---|
| Full Name | Guanylate Binding Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p22.2 |
| NCBI Gene ID | 2633 ncbi.nlm.nih.gov/gene/2633 |
| Ensembl ID | ENSG00000117228 |
| UniProt ID | P32455 |
| OMIM ID | 600411 |
| HGNC ID | 4183 |
| Aliases | GBP-1, MxA, guanylate-binding protein 1, interferon-induced guanylate-binding protein 1 |
Description
The GBP1 gene encodes guanylate binding protein 1, a member of the dynamin superfamily of large GTPases. GBP1 is strongly induced by interferons (IFN-α, IFN-β, and IFN-γ) and plays a critical role in innate immunity against intracellular pathogens, including bacteria, viruses, and parasites. It exhibits antiviral and antibacterial activity by promoting the lysis of pathogen-containing vacuoles and activating inflammasomes. Beyond its antimicrobial functions, GBP1 is involved in cell proliferation, differentiation, and inflammation, and its dysregulation has been linked to various cancers and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Infectious Diseases (e.g., Tuberculosis, Listeriosis) | GBP1 mediates host defense by disrupting pathogen-containing vacuoles and activating the inflammasome, leading to clearance of intracellular bacteria. | Functional studies in vitro and in animal models (e.g., mice deficient in GBP1 show increased susceptibility to Listeria monocytogenes and Mycobacterium tuberculosis). |
| Inflammatory Diseases (e.g., Inflammatory Bowel Disease, Rheumatoid Arthritis) | GBP1 is upregulated by inflammatory cytokines and may contribute to chronic inflammation by modulating endothelial cell responses and leukocyte adhesion. | Elevated GBP1 expression observed in inflamed tissues from patients with IBD and RA; correlation with disease severity. |
| Cancers (e.g., Ovarian, Breast, Colorectal Cancer) | GBP1 expression is often dysregulated in tumors. It can act as a tumor suppressor by inhibiting cell proliferation and angiogenesis, or as a promoter depending on the cancer type and context. | Expression profiling and clinical studies show altered GBP1 levels in various cancers; functional assays demonstrate effects on tumor cell growth and invasion. |
| Preeclampsia | GBP1 is involved in the regulation of trophoblast invasion and angiogenesis, which are critical for placental development. Dysregulation may contribute to the pathogenesis of preeclampsia. | Studies show altered GBP1 expression in placental tissues from preeclamptic pregnancies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.4 | Medium |
| Spleen | 10.1 | Medium |
| Lung | 8.2 | Medium |
| Liver | 6.5 | Low |
| Kidney | 5.1 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.3 | High expression; inducible by IFN-γ |
| THP-1 (monocytic leukemia) | 18.7 | High expression; inducible by IFN-γ and LPS |
| A549 (lung carcinoma) | 9.8 | Moderate expression; inducible by IFN-β |
| HUVEC (endothelial) | 7.2 | Moderate expression; involved in endothelial cell function |
| MCF7 (breast cancer) | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7911 (c.908A>G, p.Lys303Arg) | SNP | Minor allele frequency ~0.25 (1000 Genomes) | Associated with altered GBP1 activity and differential susceptibility to infectious diseases in some populations. |
| rs11558397 (c.1194C>T, p.Asp398=) | Synonymous SNP | Minor allele frequency ~0.05 | No known functional effect; may affect mRNA stability. |
| Somatic mutations in cancer (e.g., missense, frameshift) | Somatic | Low frequency (<1% in various cancers) | Potential loss-of-function or gain-of-function effects; not well characterized. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GBP1 are rare but may impair its GTPase activity or ability to bind membranes, leading to reduced antimicrobial activity and increased susceptibility to intracellular pathogens.
Gain of Function (GOF)
Gain-of-function mutations are not well documented. Overexpression of wild-type GBP1 is more commonly associated with pathological states, suggesting that increased activity rather than specific gain-of-function mutations drives disease.
Dominant Negative (DN)
Dominant-negative effects have not been clearly established for GBP1. However, mutations that disrupt GTP binding or hydrolysis could potentially interfere with the function of the wild-type protein in a dominant-negative manner, though this requires further investigation.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • Protein homodimerization activity | • Lipid binding |
| • Innate immune response | • Defense response to virus |
| • Defense response to bacterium | • Inflammasome complex assembly |
| • Cellular response to interferon-gamma | • Cellular response to interferon-beta |
| • Cytokine-mediated signaling pathway | • Regulation of cell proliferation |
| • Angiogenesis |
Pathways
• Interferon-gamma signaling pathway
• Interferon-alpha/beta signaling pathway
• Innate Immune System
• Inflammasome pathway
• Cytokine Signaling in Immune system
Protein Summary
GBP1 is a 67 kDa protein belonging to the dynamin superfamily of large GTPases. It is composed of a large GTPase domain at the N-terminus, a middle domain, and a C-terminal domain containing a CaaX motif for isoprenylation, which is essential for its membrane association. GBP1 hydrolyzes GTP to GDP and GMP, a unique feature among GTPases. Upon interferon stimulation, GBP1 is highly expressed and localizes to the cytoplasm and membranes of intracellular compartments. It exerts its antimicrobial effects by associating with pathogen-containing vacuoles, promoting their lysis, and releasing pathogen-associated molecular patterns (PAMPs) to activate the inflammasome. GBP1 also plays a role in regulating endothelial cell proliferation and angiogenesis, contributing to its involvement in cancer and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GBP1 Knockout HEK293 Cell Line | EDJ-KQ3004 | Human | 2633 | Details Get a Quote |
| CGGBP1 Knockout HEK293 Cell Line | EDJ-KQ6282 | Human | 8545 | Details Get a Quote |
| IGBP1C Knockout HEK293 Cell Line | EDJ-KQ13809 | Human | 645545 | Details Get a Quote |
| GBP1 Knockout A-549 Cell Line | EDJ-KQ24208 | Human | 2633 | Details Get a Quote |
| CGGBP1 Knockout A-549 Cell Line | EDJ-KQ30179 | Human | 8545 | Details Get a Quote |
| CGGBP1 Knockout HCT 116 Cell Line | EDJ-KQ30180 | Human | 8545 | Details Get a Quote |
| CGGBP1 Knockout HeLa Cell Line | EDJ-KQ30181 | Human | 8545 | Details Get a Quote |
| GBP1 Knockout HeLa Cell Line | EDJ-KQ22838 | Human | 2633 | Details Get a Quote |
| IGBP1C Knockout A-549 Cell Line | EDJ-KQ43619 | Human | 645545 | Details Get a Quote |
| IGBP1C Knockout HCT 116 Cell Line | EDJ-KQ43620 | Human | 645545 | Details Get a Quote |
| IGBP1C Knockout HeLa Cell Line | EDJ-KQ43621 | Human | 645545 | Details Get a Quote |
| GBP1 Knockout HCT 116 Cell Line | EDJ-KQ70277 | Human | 2633 | Details Get a Quote |
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