macrophage migration inhibitory factor; MIF; glycosylation-inhibiting factor; GIF; L-dopachrome isomerase; L-dopachrome tautomerase; phenylpyruvate tautomerase (MIF, GLIF, MMIF, CD74)
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Function
- pro-inflammatory cytokine
- involved in the innate immune response to bacterial pathogens
- expression of MMIF at sites of inflammation suggests a role as mediator in regulating macrophages in host defense
- counteracts the anti-inflammatory activity of glucocorticoids
- has phenylpyruvate tautomerase & dopachrome tautomerase activity (in vitro)
- physiological substrate is unknown
- not clear whether the tautomerase activity has any physiological relevance, or whether it is important for cytokine activity
- interacts with CXCR2 extracellular domain
- interacts with cell surface receptor CD74 extracellular domain, COPS5 & BNIPL
keto-phenylpyruvate = enol-phenylpyruvate
L-dopachrome = 5,6-dihydroxyindole-2-carboxylate
- KM=249 uM for phenylpyruvate
- KM=168 uM for p-hydroxyphenylpyruvate
- Vmax=2113 umol/min/mg enzyme toward phenylpyruvate
- Vmax=524 umol/min/mg enzyme toward p-hydroxyphenylpyruvate
Structure
- homotrimer.
- belongs to the MIF family
Compartment
- secreted, cytoplasm
- does not have a cleavable signal sequence & is secreted via a specialized, non-classical pathway
- secreted by macrophages upon stimulation by bacterial lipopolysaccharide (LPS), or by M tuberculosis antigens
Expression
- up-regulated in concanavalin-A-treated lymphocytes
- up-regulated in macrophages upon exposure to M tuberculosis antigens
Pathology
- a genetic variant occurs in nearly 20% of individuals
- genetic variant in MMIF is associated with susceptibility to juvenile rheumatoid arthritis
- susceptibility to COVID-19 & development of severe disease[3]
- susceptibility to inflammatory arthritis
- serum levels of MMIF are elevated in patients with severe sepsis or septic shock
Comparative biology
- gene deletion of MIF or its receptor CD74 in a T cell-dependent model of collagen-induced arthritis in mice completely eliminates arthritis development[4]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P14174.html
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/mif/
- ↑ 3.0 3.1 Shin JJ, Fan W, Par-Young J et al MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM. 2023 Mar 27;116(3):205-212. PMID: https://pubmed.ncbi.nlm.nih.gov/36222594 PMCID: PMC9620729 Free PMC article https://pmc.ncbi.nlm.nih.gov/articles/PMC9620729/
- ↑ 4.0 4.1 Doherty E, Osmani L, Bilsborrow J et al Pathogenic role of MIF receptor (CD74) expressing T cells in inflammatory arthritis. Proc Natl Acad Sci U S A. 2026 Jan 13;123(2):e2509156123. Epub 2026 Jan 8. PMID: https://pubmed.ncbi.nlm.nih.gov/41505516 PMCID: PMC12799170 (available on 2026-07-08)