Search
macrophage migration inhibitory factor; MIF; glycosylation-inhibiting factor; GIF; L-dopachrome isomerase; L-dopachrome tautomerase; phenylpyruvate tautomerase (MIF, GLIF, MMIF)
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 the CD74 extracellular domain, COPS5 & BNIPL
keto-phenylpyruvate = enol-phenylpyruvate
L-dopachrome = 5,6-dihydroxyindole-2-carboxylate
Kinetic parameters:
- 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:
- genetic variations in MMIF are associated with susceptibility to juvenile rheumatoid arthritis
- serum levels of MMIF are elevated in patients with severe sepsis or septic shock
- high levels of plasma MMIF are correlated with low survival
- drugs that inhibit tautomerase activity protect against death due to sepsis
General
cytokine
phosphoprotein
Properties
SIZE: entity length = 115 aa
MW = 12 kD
COMPARTMENT: cytoplasm
MOTIF: proline residue {P2}
binding site
SITE: 33-33
FOR-BINDING-OF: Substrate
Tyr phosphorylation site {Y37}
binding site
SITE: 65-65
FOR-BINDING-OF: Substrate; via amide nitrogen
binding site
SITE: 98-98
FOR-BINDING-OF: Substrate
Database Correlations
OMIM correlations
UniProt P14174
Pfam PF01187
Entrez Gene 4282
Kegg hsa:4282
ENZYME correlations
References
- UniProt :accession P14174
- NIEHS-SNPs
http://egp.gs.washington.edu/data/mif/