Macrophage Migration Inhibitory Factor (MIF)

GIF; GLIF; MMIF; Glycosylation-Inhibiting Factor; L-dopachrome isomerase; L-dopachrome tautomerase; Phenylpyruvate tautomerase

SPN	W114
HGNC	7097
MGI	96982
PubMed	11032394
RGD	621163
UniProt	P14174
Wiki	MIF

One of the first cytokines described, MIF (macrophage migration inhibitory factor) was originally identified in studies of delayed hypersensitivity reactions where it was shown to inhibit macrophage migration. It is an important mediator of the innate immune response with potential roles in the pathophysiology of inflammatory, autoimmune, and neoplastic disorders. The human MIF gene encodes a 115 amino acid, 12.5 kDa secreted protein. Crystallographic studies suggest that MIF exists as a homotrimer, although some reports show that it may exist as a dimer or monomer as well. Although MIF exhibits no homology with other known cytokines, it shares structural homology with several bacterial enzymes. It has been speculated that MIF is an inflammatory mediator possibly associated with rheumatoid arthritis (RA) severity.

Reference

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"Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF)."
Biochemistry 33:14144-14155(1994) [PubMed] [Europe PMC] [Abstract]

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"A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens."
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Nature 408:211-216(2000) [PubMed] [Europe PMC] [Abstract]

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"The apoptosis-associated protein BNIPL interacts with two cell proliferation-related proteins, MIF and GFER."
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"MIF signal transduction initiated by binding to CD74."
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"The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets."
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"Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor."
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"Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity."
Biochemistry 38:7346-7354(1999) [PubMed] [Europe PMC] [Abstract]

"Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography."
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"Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor."
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"Structural and kinetic analyses of macrophage migration inhibitory factor active site interactions."
Biochemistry 48:132-139(2009) [PubMed] [Europe PMC] [Abstract]

"MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations."
Proc. Natl. Acad. Sci. U.S.A. 110:10994-10999(2013) [PubMed] [Europe PMC] [Abstract]