Macrophage migration inhibitory factor(MIF)

General information on MIF protein

MIF protein also known as macrophage migration inhibitory factor, glycosylation-inhibiting factor (GIF), phenylpyruvate or L-dopachrome is a protein encoded by MIF gene in humans. The protein is part of tautomerase superfamily of proteins. The proteins belonging to this superfamily are characterized by the utilization of N-terminal protein in their mechanism. Unlike many of the proteins part of this superfamily, MIF protein is not involved in cytokine activity. The protein is believed to mediate and regulate the function of macrophages in host defense and counteracts the anti-inflammatory activity of molecules such as glucocorticoids.
nnMIF protein is released upon stimulation of white blood cells by bacterial antigens. The MIF protein then binds to CD74 protein. The latter is a transmembrane molecule expressed by B-cells, mantle cells and particularly follicular center cells. The CD74-MIF protein complex triggers an acute immune response. Glucocorticoids also stimulate MIF protein release by acting on white blood cells. MIF protein may also be released following the activation of the anterior pituary gland as a result trauma.
nnMIF protein assembles into a trimer that consists of three identical subunits. Each monomer contain a four-stranded beta sheet and two antiparallel alpha helices. The monomers are located around a central channel with 3-fold rational symmetry.
nnMIF proteins contains two motifs responsible for its catalytic activity. One of the motifs has 27 amino acids and is located at the N-terminus of the protein chain. It functions as a phenylpyruvate tautomerase and catalyzes the conversion of 2-carboxy-2,3-dihydroindole-5,6-quinone (also known as dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (also known as DHICA). The other catalytic site is located between residues 57 and 60 and appears to act as a disulfide reductase. MIF protein has been reported to interact with a range of proteins such as BNIPL, CD74, COPS5, CXCR4 and RPS19. MIF protein has been considered as a potential drug target for cancer, sepsis and rheumatoid arthritis.