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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1 337 1
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.  
3
  • CuratedUniProtKB
GO molecular function 
Chemoattractant activitydefinition[GO:0042056]  
1
  • IDABHF-UCL
Cytokine activitydefinition[GO:0005125]  
1
  • IDAUniProtKB
Cytokine receptor bindingdefinition[GO:0005126]  
1
  • IPIBHF-UCL
Dopachrome isomerase activitydefinition[GO:0004167]  
1
  • IDAUniProtKB
Phenylpyruvate tautomerase activitydefinition[GO:0050178]  
1
  • IDAMGI
Protein bindingdefinition[GO:0005515]  
3
  • IPIIntAct
  • IPIBHF-UCL
  • IPIUniProtKB
Receptor bindingdefinition[GO:0005102]  
1
  • IPIBHF-UCL
GO biological process 
Carboxylic acid metabolic processdefinition[GO:0019752]  
1
  • IDABHF-UCL
Cell agingdefinition[GO:0007569] silver  
  • IEAOrtholog Compara
Cell proliferationdefinition[GO:0008283]  
1
  • IDAUniProtKB
Cell surface receptor signaling pathwaydefinition[GO:0007166]  
1
  • IDAUniProtKB
DNA damage response, signal transduction by p53 class mediatordefinition[GO:0030330] silver  
  • IEAOrtholog Compara
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Innate immune responsedefinition[GO:0045087]  
  • IEAUniProtKB KW
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IDAUniProtKB
Negative regulation of cell agingdefinition[GO:0090344]  
1
  • IDABHF-UCL
Negative regulation of cell cycle arrestdefinition[GO:0071157]  
1
  • IDABHF-UCL
Negative regulation of cellular protein metabolic processdefinition[GO:0032269] silver  
  • IEAOrtholog Compara
Negative regulation of DNA damage response, signal transduction by p53 class mediatordefinition[GO:0043518]  
1
  • IDABHF-UCL
Negative regulation of gene expressiondefinition[GO:0010629]  
1
  • IDABHF-UCL
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:1902166]  
1
  • IDABHF-UCL
Negative regulation of mature B cell apoptotic processdefinition[GO:0002906] silver  
  • IEAOrtholog Compara
Negative regulation of myeloid cell apoptotic processdefinition[GO:0033033] silver  
  • IEAOrtholog Compara
Positive chemotaxisdefinition[GO:0050918]  
1
  • IDAGOC
Positive regulation of arachidonic acid secretiondefinition[GO:0090238] silver  
  • IEAOrtholog Compara
Positive regulation of B cell proliferationdefinition[GO:0030890]  
1
  • IDABHF-UCL
Positive regulation of chemokine (C-X-C motif) ligand 2 productiondefinition[GO:2000343] silver  
  • IEAOrtholog Compara
Positive regulation of cytokine secretiondefinition[GO:0050715]  
1
  • IDABHF-UCL
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
2
  • IDABHF-UCL
Positive regulation of fibroblast proliferationdefinition[GO:0048146]  
1
  • IDABHF-UCL
Positive regulation of lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031666] silver  
  • IEAOrtholog Compara
Positive regulation of MAP kinase activitydefinition[GO:0043406] silver  
  • IEAOrtholog Compara
Positive regulation of myeloid leukocyte cytokine production involved in immune responsedefinition[GO:0061081] silver  
  • IEAOrtholog Compara
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
1
  • IDABHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • IDABHF-UCL
Positive regulation of phosphorylationdefinition[GO:0042327]  
1
  • IDABHF-UCL
Positive regulation of prostaglandin secretion involved in immune responsedefinition[GO:0061078] silver  
  • IEAOrtholog Compara
Positive regulation of protein kinase A signalingdefinition[GO:0010739]  
1
  • IDABHF-UCL
Prostaglandin biosynthetic processdefinition[GO:0001516]  
1
  • IDAUniProtKB
Protein homotrimerizationdefinition[GO:0070207]  
1
  • IPIUniProtKB
Regulation of macrophage activationdefinition[GO:0043030]  
1
  • NASUniProtKB
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.  
3
  • CuratedUniProtKB
EC 5.3.3.12: L-dopachrome 5,6-dihydroxyindole-2-carboxylate.  
3
  • CuratedUniProtKB
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.  
  • CuratedUniProtKB
 

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