Macrophage migration inhibitory factor

Details

Name
Macrophage migration inhibitory factor
Synonyms
  • 5.3.2.1
  • GIF
  • GLIF
  • Glycosylation-inhibiting factor
  • L-dopachrome isomerase
  • L-dopachrome tautomerase
  • MIF
  • MMIF
  • Phenylpyruvate tautomerase
Gene Name
MIF
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020563|Macrophage migration inhibitory factor
MPMFIVNTNVPRASVPDGFLSELTQQLAQATGKPPQYIAVHVVPDQLMAFGGSSEPCALC
SLHSIGKIGGAQNRSYSKLLCGLLAERLRISPDRVYINYYDMNAANVGWNNSTFA
Number of residues
115
Molecular Weight
12476.19
Theoretical pI
8.05
GO Classification
Functions
chemoattractant activity / cytokine activity / cytokine receptor binding / dopachrome isomerase activity / phenylpyruvate tautomerase activity / receptor binding
Processes
carboxylic acid metabolic process / cell aging / cell proliferation / cell surface receptor signaling pathway / DNA damage response, signal transduction by p53 class mediator / inflammatory response / innate immune response / negative regulation of apoptotic process / negative regulation of cell aging / negative regulation of cell cycle arrest / negative regulation of cellular protein metabolic process / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of gene expression / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / negative regulation of mature B cell apoptotic process / negative regulation of myeloid cell apoptotic process / positive chemotaxis / positive regulation of arachidonic acid secretion / positive regulation of B cell proliferation / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of cytokine secretion / positive regulation of ERK1 and ERK2 cascade / positive regulation of fibroblast proliferation / positive regulation of lipopolysaccharide-mediated signaling pathway / positive regulation of MAP kinase activity / positive regulation of myeloid leukocyte cytokine production involved in immune response / positive regulation of peptidyl-serine phosphorylation / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of prostaglandin secretion involved in immune response / positive regulation of protein kinase A signaling / prostaglandin biosynthetic process / protein homotrimerization / regulation of macrophage activation
Components
cell surface / cytoplasm / extracellular exosome / extracellular region / extracellular space / myelin sheath / nucleoplasm / vesicle
General Function
Receptor binding
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0020564|Macrophage migration inhibitory factor (MIF)
ATGCCGATGTTCATCGTAAACACCAACGTGCCCCGCGCCTCCGTGCCGGACGGGTTCCTC
TCCGAGCTCACCCAGCAGCTGGCGCAGGCCACCGGCAAGCCCCCCCAGTACATCGCGGTG
CACGTGGTCCCGGACCAGCTCATGGCCTTCGGCGGCTCCAGCGAGCCGTGCGCGCTCTGC
AGCCTGCACAGCATCGGCAAGATCGGCGGCGCGCAGAACCGCTCCTACAGCAAGCTGCTG
TGCGGCCTGCTGGCCGAGCGCCTGCGCATCAGCCCGGACAGGGTCTACATCAACTATTAC
GACATGAACGCGGCCAATGTGGGCTGGAACAACTCCACCTTCGCCTAA
Chromosome Location
22
Locus
22q11.23
External Identifiers
ResourceLink
UniProtKB IDP14174
UniProtKB Entry NameMIF_HUMAN
GenBank Protein ID188556
GenBank Gene IDM25639
GenAtlas IDMIF
HGNC IDHGNC:7097
General References
  1. Weiser WY, Temple PA, Witek-Giannotti JS, Remold HG, Clark SC, David JR: Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7522-6. [Article]
  2. Mikayama T, Nakano T, Gomi H, Nakagawa Y, Liu YC, Sato M, Iwamatsu A, Ishii Y, Weiser WY, Ishizaka K: Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10056-60. [Article]
  3. Bernhagen J, Mitchell RA, Calandra T, Voelter W, Cerami A, Bucala R: Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF). Biochemistry. 1994 Nov 29;33(47):14144-55. [Article]
  4. Paralkar V, Wistow G: Cloning the human gene for macrophage migration inhibitory factor (MIF). Genomics. 1994 Jan 1;19(1):48-51. [Article]
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  10. Zeng FY, Weiser WY, Kratzin H, Stahl B, Karas M, Gabius HJ: The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor. Arch Biochem Biophys. 1993 May 15;303(1):74-80. [Article]
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  12. Kleemann R, Hausser A, Geiger G, Mischke R, Burger-Kentischer A, Flieger O, Johannes FJ, Roger T, Calandra T, Kapurniotu A, Grell M, Finkelmeier D, Brunner H, Bernhagen J: Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature. 2000 Nov 9;408(6809):211-6. [Article]
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  14. Tan TH, Edgerton SA, Kumari R, McAlister MS, Roe SM, Nagl S, Pearl LH, Selkirk ME, Bianco AE, Totty NF, Engwerda C, Gray CA, Meyer DJ: Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis. Biochem J. 2001 Jul 15;357(Pt 2):373-83. [Article]
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  16. Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R: MIF signal transduction initiated by binding to CD74. J Exp Med. 2003 Jun 2;197(11):1467-76. [Article]
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  26. Sugimoto H, Suzuki M, Nakagawa A, Tanaka I, Nishihira J: Crystal structure of macrophage migration inhibitory factor from human lymphocyte at 2.1 A resolution. FEBS Lett. 1996 Jul 1;389(2):145-8. [Article]
  27. Kato Y, Muto T, Tomura T, Tsumura H, Watarai H, Mikayama T, Ishizaka K, Kuroki R: The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3007-10. [Article]
  28. Sun HW, Bernhagen J, Bucala R, Lolis E: Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5191-6. [Article]
  29. Lubetsky JB, Swope M, Dealwis C, Blake P, Lolis E: Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity. Biochemistry. 1999 Jun 1;38(22):7346-54. [Article]
  30. Orita M, Yamamoto S, Katayama N, Aoki M, Takayama K, Yamagiwa Y, Seki N, Suzuki H, Kurihara H, Sakashita H, Takeuchi M, Fujita S, Yamada T, Tanaka A: Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography. J Med Chem. 2001 Feb 15;44(4):540-7. [Article]
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  33. Fan C, Rajasekaran D, Syed MA, Leng L, Loria JP, Bhandari V, Bucala R, Lolis EJ: MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations. Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):10994-9. doi: 10.1073/pnas.1221817110. Epub 2013 Jun 17. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB027287-Hydroxy-2-Oxo-Chromene-3-Carboxylic Acid Ethyl EsterexperimentalunknownDetails
DB018803,4-Dihydroxycinnamic Acidexperimental, investigationalunknownDetails
DB077184-Hydroxyphenylpyruvic acidexperimentalunknownDetails
DB078883-(4-HYDROXYPHENYL)-4,5-DIHYDRO-5-ISOXAZOLE-ACETIC ACID METHYL ESTERexperimentalunknownDetails
DB083334-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIMEexperimentalunknownDetails
DB083343-FLUORO-4-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIMEexperimentalunknownDetails
DB083354-HYDROXYBENZALDEHYDE O-(3,3-DIMETHYLBUTANOYL)OXIMEexperimentalunknownDetails
DB087656-HYDROXY-1,3-BENZOTHIAZOLE-2-SULFONAMIDEexperimentalunknownDetails