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Glucose-6-phosphate isomerase (GPI) is a glycolytic enzyme that catalyzes the conversion of D-glucose-6-phosphate (Item No. 20376) to D-fructose-6-phosphate.1,2 It exists as a dimer where each monomer is composed of a large and small globular domain, which form a cleft that contains the catalytic active site, and a C-terminal tail.2,3 GPI is ubiquitously expressed and localized to the cytoplasm.1,2 It also functions as a neurotrophic growth factor and has a role in immunoglobulin synthesis.2 GPI is an autoantigen in rheumatoid arthritis (RA).4 Immunization with recombinant human GPI induces inflammatory cell infiltration, cartilage destruction, and bone erosion in the inflamed joints of mice, an effect that is reduced in Padi4 knockout mice, which lack peptidyl arginine deiminase 4 (PAD4), an enzyme involved in protein citrullination.5 Citrullinated GPI autoantibodies have been found in the serum of patients RA.4
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1. Autoantibodies to GPI in rheumatoid arthritis: Linkage between an animal model and human disease. Nat. Immunol. 2(8), 746-753 (2001).
2. The crystal structure of a multifunctional protein: Phosphoglucose isomerase/autocrine motility factor/neuroleukin. Proc. Natl. Acad. Sci. USA 96(10), 5412-5417 (1999).
3. The crystal structure of glucose-
4. Anti-
5. Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-