Guanylate-binding protein 1 (GBP1)

Guanylate-binding protein 1 (GBP1) is a large, interferon-inducible GTPase that plays a key role in cell-intrinsic immunity against intracellular pathogens, such as bacteria and viruses[3][4]. Structurally, GBP1 consists of an N-terminal large GTPase domain and a C-terminal helical domain with a CaaX isoprenylation site, which regulates membrane binding. Upon GTP binding, GBP1 undergoes nucleotide-dependent conformational changes, dimerizes, oligomerizes, and forms scaffold-like coats around target membranes—including those of cytosolic bacteria—thus restricting their replication and promoting their clearance[3][4]. GBP1 is regulated by inflammatory cytokines (especially IFNγ), as well as by stress-related transcription factors like p53 and the p38-MAPK pathway[2]. It also regulates cell survival, apoptosis, cytoskeletal organization, and acts as a key modulator of inflammation and cellular stress responses. In tumors, GBP1's role is complex, functioning as both a tumor suppressor and a facilitator of chemoresistance, depending on context[2]. No direct small-molecule drugs currently target GBP1, but its expression is being explored as a biomarker and its pathways may represent future therapeutic opportunities.

Other names

Guanylate-binding protein 1GBP1GBP-1HuGBP-1hGBP1GTP-binding protein 1Guanine nucleotide-binding protein 1Interferon-induced guanylate-binding protein 1interferon-inducible guanylate-binding protein 167kDa GBPhuGBP-1

GTPase activity (hydrolyzes GTP to GDP and GMP). Oligomerization and membrane coat assembly to encapsulate pathogens. Association with membrane lipids (isoprenylation/farnesylation allowing membrane binding). Regulation via IFNγ pathway, p53, and p38-MAPK.