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Gene Review

GBP1  -  guanylate binding protein 1, interferon...

Homo sapiens

Synonyms: GBP-1, GTP-binding protein 1, Guanine nucleotide-binding protein 1, HuGBP-1, Interferon-induced guanylate-binding protein 1
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Disease relevance of GBP1


Psychiatry related information on GBP1


High impact information on GBP1

  • Further studies localized the defect in signal transduction to the interaction between cell-surface receptors and the guanine nucleotide-binding protein [10].
  • Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2 [11].
  • From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity [11].
  • Odorant activation of the enzyme is ligand and tissue specific, and occurs only in the presence of GTP, suggesting the involvement of receptor(s) coupled to a guanine nucleotide binding protein (G-protein) [12].
  • These findings strongly support the idea that the coupling factor linking receptor and PPI phosphodiesterase is a guanine nucleotide binding protein analogous to those involved in the activation and inhibition of adenylate cyclase [13].

Chemical compound and disease context of GBP1


Biological context of GBP1

  • Analysis of endometrial biopsies by Northern blotting and RT-PCR demonstrated that GBP1 mRNA is specifically induced at the midsecretory phase of the menstrual cycle [19].
  • We have isolated DNA clones containing the interferon (IFN)-inducible guanylate-binding protein-1-encoding gene (GBP1) from a human genomic library [1].
  • The interferon-inducible GBP1 gene: structure and mapping to human chromosome 1 [1].
  • The 2880 bp corresponding to the GBP1 cDNA were subdivided into eleven exons which were interrupted by a total of 9500 bp of intron DNA [1].
  • GBP1 overexpression is associated with a paclitaxel resistance phenotype [2].

Anatomical context of GBP1


Associations of GBP1 with chemical compounds

  • Here we present the structure of human GBP1 in complex with the non-hydrolysable GTP analogue GppNHp [21].
  • Parallel analysis of the Cancer Cell Line Profiling Array determined that GBP1 expression in a majority of cell lines derived from human tumors of different tissue origin was induced to variable levels following exposure to multiple stress agents including paclitaxel and doxorubicin [2].
  • These two mutants had a dominant-negative effect, preventing endogenous wild-type hGBP-1 from efficiently redistributing after aluminum fluoride treatment [22].
  • Guanylate-binding proteins (GBPs) were originally described as proteins that are strongly induced by interferons and are capable of binding to agarose-immobilized guanine nucleotides. hGBP1, the first of two members of this protein family in humans, was recently shown to represent a novel type of GTPase that hydrolyzes GTP predominantly to GMP [23].
  • A conserved tyrosine kinase-activated signal transduction pathway has recently been identified that comprises the plasma membrane-bound small guanine-nucleotide-binding protein Ras and the protein kinases Raf, MAP-kinase kinase and MAP kinase [24].

Physical interactions of GBP1


Enzymatic interactions of GBP1


Regulatory relationships of GBP1


Other interactions of GBP1


Analytical, diagnostic and therapeutic context of GBP1


  1. The interferon-inducible GBP1 gene: structure and mapping to human chromosome 1. Strehlow, I., Lohmann-Matthes, M.L., Decker, T. Gene (1994) [Pubmed]
  2. GBP1 overexpression is associated with a paclitaxel resistance phenotype. Duan, Z., Foster, R., Brakora, K.A., Yusuf, R.Z., Seiden, M.V. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  3. The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines. Guenzi, E., Töpolt, K., Cornali, E., Lubeseder-Martellato, C., Jörg, A., Matzen, K., Zietz, C., Kremmer, E., Nappi, F., Schwemmle, M., Hohenadl, C., Barillari, G., Tschachler, E., Monini, P., Ensoli, B., Stürzl, M. EMBO J. (2001) [Pubmed]
  4. Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases. Lubeseder-Martellato, C., Guenzi, E., Jörg, A., Töpolt, K., Naschberger, E., Kremmer, E., Zietz, C., Tschachler, E., Hutzler, P., Schwemmle, M., Matzen, K., Grimm, T., Ensoli, B., Stürzl, M. Am. J. Pathol. (2002) [Pubmed]
  5. Mononuclear leukocyte levels of G proteins in depressed patients with bipolar disorder or major depressive disorder. Young, L.T., Li, P.P., Kamble, A., Siu, K.P., Warsh, J.J. The American journal of psychiatry. (1994) [Pubmed]
  6. The nature of bipolar disorder. Manji, H.K., Lenox, R.H. The Journal of clinical psychiatry. (2000) [Pubmed]
  7. Rapid stimulation of amyloid precursor protein release by epidermal growth factor: role of protein kinase C. Slack, B.E., Breu, J., Muchnicki, L., Wurtman, R.J. Biochem. J. (1997) [Pubmed]
  8. Coupling of D1 dopamine receptors to the guanine nucleotide binding protein Gs is deficient in Huntington's disease. De Keyser, J., De Backer, J.P., Ebinger, G., Vauquelin, G. Brain Res. (1989) [Pubmed]
  9. Nucleotide binding and self-stimulated GTPase activity of human guanylate-binding protein 1 (hGBP1). Kunzelmann, S., Praefcke, G.J., Herrmann, C. Meth. Enzymol. (2005) [Pubmed]
  10. An immunodeficiency characterized by defective signal transduction in T lymphocytes. Chatila, T., Wong, R., Young, M., Miller, R., Terhorst, C., Geha, R.S. N. Engl. J. Med. (1989) [Pubmed]
  11. Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Prakash, B., Praefcke, G.J., Renault, L., Wittinghofer, A., Herrmann, C. Nature (2000) [Pubmed]
  12. Odorant-sensitive adenylate cyclase may mediate olfactory reception. Pace, U., Hanski, E., Salomon, Y., Lancet, D. Nature (1985) [Pubmed]
  13. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Cockcroft, S., Gomperts, B.D. Nature (1985) [Pubmed]
  14. Atrial natriuretic factor reduces cyclic adenosine monophosphate content of human fibroblasts by enhancing phosphodiesterase activity. Lee, M.A., West, R.E., Moss, J. J. Clin. Invest. (1988) [Pubmed]
  15. Inositol 1,4,5-triphosphate-induced granule secretion in platelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptors involves a guanine nucleotide binding protein-dependent mechanism distinct from that of thrombin. Brass, L.F., Shaller, C.C., Belmonte, E.J. J. Clin. Invest. (1987) [Pubmed]
  16. Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL-60) cells. Brandt, S.J., Dougherty, R.W., Lapetina, E.G., Niedel, J.E. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  17. Evidence that a guanine nucleotide-binding protein linked to a muscarinic receptor inhibits directly phospholipase C. Bizzarri, C., Di Girolamo, M., D'Orazio, M.C., Corda, D. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  18. 2-Azido-[32P]NAD+, a photoactivatable probe for G-protein structure: evidence for holotransducin oligomers in which the ADP-ribosylated carboxyl terminus of alpha interacts with both alpha and gamma subunits. Vaillancourt, R.R., Dhanasekaran, N., Johnson, G.L., Ruoho, A.E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  19. Messenger ribonucleic acid encoding interferon-inducible guanylate binding protein 1 is induced in human endometrium within the putative window of implantation. Kumar, S., Li, Q., Dua, A., Ying, Y.K., Bagchi, M.K., Bagchi, I.C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  20. Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1. Nantais, D.E., Schwemmle, M., Stickney, J.T., Vestal, D.J., Buss, J.E. J. Leukoc. Biol. (1996) [Pubmed]
  21. Triphosphate structure of guanylate-binding protein 1 and implications for nucleotide binding and GTPase mechanism. Prakash, B., Renault, L., Praefcke, G.J., Herrmann, C., Wittinghofer, A. EMBO J. (2000) [Pubmed]
  22. Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor. Modiano, N., Lu, Y.E., Cresswell, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  23. GTPase properties of the interferon-induced human guanylate-binding protein 2. Neun, R., Richter, M.F., Staeheli, P., Schwemmle, M. FEBS Lett. (1996) [Pubmed]
  24. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Leevers, S.J., Paterson, H.F., Marshall, C.J. Nature (1994) [Pubmed]
  25. Nuclear factor-kappaB motif and interferon-alpha-stimulated response element co-operate in the activation of guanylate-binding protein-1 expression by inflammatory cytokines in endothelial cells. Naschberger, E., Werner, T., Vicente, A.B., Guenzi, E., Töpolt, K., Leubert, R., Lubeseder-Martellato, C., Nelson, P.J., Stürzl, M. Biochem. J. (2004) [Pubmed]
  26. Guanine nucleotide-binding protein interacting but unstimulating sequence located in insulin-like growth factor II receptor. Its autoinhibitory characteristics and structural determinants. Nishimoto, I., Ogata, E., Okamoto, T. J. Biol. Chem. (1991) [Pubmed]
  27. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Lee, M.J., Van Brocklyn, J.R., Thangada, S., Liu, C.H., Hand, A.R., Menzeleev, R., Spiegel, S., Hla, T. Science (1998) [Pubmed]
  28. Solubilization of human placental tumor necrosis factor receptors as a complex with a guanine nucleotide-binding protein. Hayakawa, M., Hori, T., Shibamoto, S., Tsujimoto, M., Oku, N., Ito, F. Arch. Biochem. Biophys. (1991) [Pubmed]
  29. Characterization of the binding of a potent, selective, radioiodinated antagonist to the human neurokinin-1 receptor. Cascieri, M.A., Ber, E., Fong, T.M., Sadowski, S., Bansal, A., Swain, C., Seward, E., Frances, B., Burns, D., Strader, C.D. Mol. Pharmacol. (1992) [Pubmed]
  30. Protein kinase cross-talk: membrane targeting of the beta-adrenergic receptor kinase by protein kinase C. Winstel, R., Freund, S., Krasel, C., Hoppe, E., Lohse, M.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  31. Activation of Pyk2 by stress signals and coupling with JNK signaling pathway. Tokiwa, G., Dikic, I., Lev, S., Schlessinger, J. Science (1996) [Pubmed]
  32. The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway. Cortez, D., Stoica, G., Pierce, J.H., Pendergast, A.M. Oncogene (1996) [Pubmed]
  33. Mutational analysis of phospholipase C-beta 2. Identification of regions required for membrane association and stimulation by guanine-nucleotide-binding protein beta gamma subunits. Schnabel, P., Camps, M., Carozzi, A., Parker, P.J., Gierschik, P. Eur. J. Biochem. (1993) [Pubmed]
  34. Antisera against a guanine nucleotide binding protein from retina cross-react with the beta subunit of the adenylyl cyclase-associated guanine nucleotide binding proteins, Ns and Ni. Gierschik, P., Codina, J., Simons, C., Birnbaumer, L., Spiegel, A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  35. cGMP influences guanine nucleotide binding to frog photoreceptor G-protein. Robinson, P.R., Radeke, M.J., Cote, R.H., Bownds, M.D. J. Biol. Chem. (1986) [Pubmed]
  36. The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression. Guenzi, E., Töpolt, K., Lubeseder-Martellato, C., Jörg, A., Naschberger, E., Benelli, R., Albini, A., Stürzl, M. EMBO J. (2003) [Pubmed]
  37. Materials specificity and directed assembly of a gold-binding peptide. Tamerler, C., Duman, M., Oren, E.E., Gungormus, M., Xiong, X., Kacar, T., Parviz, B.A., Sarikaya, M. Small (Weinheim an der Bergstrasse, Germany) (2006) [Pubmed]
  38. Characterization by two-dimensional peptide mapping of the gamma subunits of Ns and Ni, the regulatory proteins of adenylyl cyclase, and of transducin, the guanine nucleotide-binding protein of rod outer segments of the eye. Hildebrandt, J.D., Codina, J., Rosenthal, W., Birnbaumer, L., Neer, E.J., Yamazaki, A., Bitensky, M.W. J. Biol. Chem. (1985) [Pubmed]
  39. Nucleotide-binding characteristics of human guanylate-binding protein 1 (hGBP1) and identification of the third GTP-binding motif. Praefcke, G.J., Geyer, M., Schwemmle, M., Robert Kalbitzer, H., Herrmann, C. J. Mol. Biol. (1999) [Pubmed]
  40. Expression of functional stimulatory guanine nucleotide binding protein in nonfunctioning thyroid adenomas is not correlated to adenylate cyclase activity and growth of these tumors. Hamacher, C., Studer, H., Zbaeren, J., Schatz, H., Derwahl, M. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
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