MIF - Macrophage migration inhibitory factor - human protein (Function)
 
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MIF »  Macrophage migration inhibitory factor   [ EC 5.3.2.1 ]  (MIF)
 
Protein also known as:  Glycosylation-inhibiting factor (GIF).
Gene name:  MIF
Family name: MIF
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.  
4
  • UniProtKB
GO molecular function 
Chemoattractant activitydefinition[GO:0042056]  
1
  • BHF-UCL
Cytokine activitydefinition[GO:0005125]  
1
  • UniProtKB
Cytokine receptor bindingdefinition[GO:0005126]  
1
  • BHF-UCL
Dopachrome isomerase activitydefinition[GO:0004167]  
1
  • UniProtKB
Phenylpyruvate tautomerase activitydefinition[GO:0050178]  
1
  • MGI
Protein bindingdefinition[GO:0005515]  
3
  • IntAct
  • BHF-UCL
  • UniProtKB
Receptor bindingdefinition[GO:0005102]  
1
  • BHF-UCL
GO biological process 
Carboxylic acid metabolic processdefinition[GO:0019752]  
1
  • BHF-UCL
Cell agingdefinition[GO:0007569] silver  
1
  • Ortholog Compara
Cell proliferationdefinition[GO:0008283]  
1
  • UniProtKB
Cell surface receptor signaling pathwaydefinition[GO:0007166]  
1
  • UniProtKB
DNA damage response, signal transduction by p53 class mediatordefinition[GO:0030330] silver  
1
  • Ortholog Compara
Inflammatory responsedefinition[GO:0006954]  
1
  • UniProtKB KW
Innate immune responsedefinition[GO:0045087]  
1
  • UniProtKB KW
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • UniProtKB
Negative regulation of cell agingdefinition[GO:0090344]  
1
  • BHF-UCL
Negative regulation of cell cycle arrestdefinition[GO:0071157]  
1
  • BHF-UCL
Negative regulation of cellular protein metabolic processdefinition[GO:0032269] silver  
1
  • Ortholog Compara
Negative regulation of DNA damage response, signal transduction by p53 class mediatordefinition[GO:0043518]  
1
  • BHF-UCL
Negative regulation of gene expressiondefinition[GO:0010629]  
1
  • BHF-UCL
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:1902166]  
1
  • BHF-UCL
Negative regulation of mature B cell apoptotic processdefinition[GO:0002906] silver  
1
  • Ortholog Compara
Negative regulation of myeloid cell apoptotic processdefinition[GO:0033033] silver  
1
  • Ortholog Compara
Positive chemotaxisdefinition[GO:0050918]  
1
  • GOC
Positive regulation of arachidonic acid secretiondefinition[GO:0090238] silver  
1
  • Ortholog Compara
Positive regulation of B cell proliferationdefinition[GO:0030890]  
1
  • BHF-UCL
Positive regulation of chemokine (C-X-C motif) ligand 2 productiondefinition[GO:2000343] silver  
1
  • Ortholog Compara
Positive regulation of cytokine secretiondefinition[GO:0050715]  
1
  • BHF-UCL
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
2
  • BHF-UCL
Positive regulation of fibroblast proliferationdefinition[GO:0048146]  
1
  • BHF-UCL
Positive regulation of lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031666] silver  
1
  • Ortholog Compara
Positive regulation of MAP kinase activitydefinition[GO:0043406] silver  
1
  • Ortholog Compara
Positive regulation of myeloid leukocyte cytokine production involved in immune responsedefinition[GO:0061081] silver  
1
  • Ortholog Compara
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
1
  • BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • BHF-UCL
Positive regulation of phosphorylationdefinition[GO:0042327]  
1
  • BHF-UCL
Positive regulation of prostaglandin secretion involved in immune responsedefinition[GO:0061078] silver  
1
  • Ortholog Compara
Positive regulation of protein kinase A signalingdefinition[GO:0010739]  
1
  • BHF-UCL
Prostaglandin biosynthetic processdefinition[GO:0001516]  
1
  • UniProtKB
Protein homotrimerizationdefinition[GO:0070207]  
1
  • UniProtKB
Regulation of macrophage activationdefinition[GO:0043030]  
1
  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 5.3.2.1: Keto-phenylpyruvate enol-phenylpyruvate.  
1
  • UniProtKB
EC 5.3.3.12: L-dopachrome 5,6-dihydroxyindole-2-carboxylate.  
1
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Phenylalanine metabolism  hsa00360+4282  
Tyrosine metabolism  hsa00350+4282  
Note 
Serum levels of MIF are elevated in patients with severe sepsis or septic shock. High levels of MIF are correlated with low survival. Drugs that inhibit tautomerase activity protect against death due to sepsis.  
1
  • UniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 168 uM for p-hydroxyphenylpyruvate
KM 249 uM for phenylpyruvate
Vmax 2113 umol/min/mg enzyme toward phenylpyruvate
Vmax 524 umol/min/mg enzyme toward p-hydroxyphenylpyruvate

Keywords

Biological process 
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Molecular function 
Cytokine  definition   [KW-0202]
Isomerase  definition   [KW-0413]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links