Migration Inhibitory Factor (MIF) Recombinant Protein

This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]

Function: Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity. Ref.23 Ref.24

Catalytic activity: Keto-phenylpyruvate = enol-phenylpyruvate. Ref.32 Ref.34L-dopachrome = 5,6-dihydroxyindole-2-carboxylate. Ref.32 Ref.34

Subunit structure: Homotrimer. Interacts with CXCR2 extracellular domain

By similarity. Interacts with the CD74 extracellular domain, COPS5 and BNIPL. Ref.18 Ref.21 Ref.22 Ref.25 Ref.33 Ref.34

Subcellular location: Secreted. Cytoplasm. Note: Does not have a cleavable signal sequence and is secreted via a specialized, non-classical pathway. Secreted by macrophages upon stimulation by bacterial lipopolysaccharide (LPS), or by M.tuberculosis antigens. Ref.1 Ref.2 Ref.18 Ref.23 Ref.25

Induction: Up-regulated in concanavalin-A-treated lymphocytes. Up-regulated in macrophages upon exposure to M.tuberculosis antigens. Ref.1 Ref.23

Involvement in disease: Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Miscellaneous: Serum levels of MIF are elevated in patients with severe sepsis or septic shock. High levels of MIF are correlated with low survival. Drugs that inhibit tautomerase activity protect against death due to sepsis.

Sequence similarities: Belongs to the MIF family.

Biophysicochemical propertiesKinetic parameters:KM=249 µM for phenylpyruvate Ref.20KM=168 µM for p-hydroxyphenylpyruvateVmax=2113 µmol/min/mg enzyme toward phenylpyruvateVmax=524 µmol/min/mg enzyme toward p-hydroxyphenylpyruvate