Macrophage migration inhibitory factor

Macrophage migration inhibitory factor (MIF or MMIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the MIF gene. MIF is an important regulator of innate immunity. The MIF protein superfamily also includes a second member with functionally related properties, the D-dopachrome tautomerase (D-DT).1ca7: MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE1cgq: MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH ALANINE INSERTED BETWEEN PRO-1 AND MET-21gcz: MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) COMPLEXED WITH INHIBITOR.1gd0: HUMAN MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)1gif: HUMAN GLYCOSYLATION-INHIBITING FACTOR1ljt: Crystal Structure of Macrophage Migration Inhibitory Factor complexed with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole-acetic acid methyl ester (ISO-1)1mif: MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)1p1g: MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH PRO-1 MUTATED TO GLY-12ooh: Crystal Structure of MIF bound to a Novel Inhibitor, OXIM-112oow: MIF Bound to a Fluorinated OXIM Derivative2ooz: Macrophage Migration Inhibitory Factor (MIF) Complexed with OXIM6 (an OXIM Derivative Not Containing a Ring in its R-group) Macrophage migration inhibitory factor (MIF or MMIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the MIF gene. MIF is an important regulator of innate immunity. The MIF protein superfamily also includes a second member with functionally related properties, the D-dopachrome tautomerase (D-DT). Bacterial antigens stimulate white blood cells to release MIF into the blood stream. The circulating MIF binds to CD74 on other immune cells to trigger an acute immune response. Hence, MIF is classified as an inflammatory cytokine. Furthermore, glucocorticoids also stimulate white blood cells to release MIF and hence MIF partially counteracts the inhibitory effects that glucocorticoids have on the immune system. Finally trauma activates the anterior pituitary gland to release MIF. Macrophage migration inhibitory factor assembles into a trimer composed of three identical subunits. Each of these monomers contain two antiparallel alpha helices and a four-stranded beta sheet. The monomers surround a central channel with 3-fold rotational symmetry. MIF contains two motifs with catalytic activity. The first is a 27 amino acid motif located at the N-terminus functions as a phenylpyruvate tautomerase that can catalyze the conversion of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). MIF also contains a Cys-Ala-Leu-Cys catalytic site between residues 57 and 60 that appears to function as a disulfide reductase. This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. MIF 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 a role in integrin signaling pathways. MIF binds to CD74, inducing its phosphorylation and the recruitment of CD44 which then activates non-receptor tyrosine kinases, leading ultimately to extracellular signal-regulated kinase phosphorylation. Macrophage migration inhibitory factor has been reported to interact with: MIF is a potential drug target for sepsis, rheumatoid arthritis, and cancer. Multiple protozoan parasites produce homologs MIF that have similar inflammatory functions to human MIF, and play a role in their pathogenesis, invasion and immune evasion. Examples of protozoans with MIF homologs that have been reported: