The present invention provides polynucleotides encoding human and murine guanylate binding protein polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The present invention further relates to diagnostic and therapeutic methods for applying the guanylate binding protein polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides, such as rheumatoid arthritis and/or conditions related to aberrant NF-.kappa.B activity, guanylate binding activity and GTPase activity. The present invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.