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InterPro: IPR001398 Macrophage migration inhibitory factor
Protein matches
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UniProtKB Matches: 372 proteins |
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Accession
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IPR001398 Macrophage_inhib_fac |
Type
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Family |
Signatures
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InterPro Relationships
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Parent
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IPR014347 Tautomerase
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Contains
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IPR019829 Macrophage migration inhibitory factor, conserved site
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InterPro annotation
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Entry Details in BioMart
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Abstract
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Macrophage migration inhibitory factor (MIF) is a key regulatory cytokine within innate and adaptive immune responses, capable of promoting and modulating the magnitude of the response [1]. MIF is released from T-cells and macrophages, and acts within the neuroendocrine system. MIF is capable of tautomerase activity, although its biological function has not been fully characterised. It is induced by glucocorticoid and is capable of overriding the anti-inflammatory actions of glucocorticoid [2]. MIF regulates cytokine secretion and the expression of receptors involved in the immune response. It can be taken up into target cells in order to interact with intracellular signalling molecules, inhibiting p53 function, and/or activating components of the mitogen-activated protein kinase and Jun-activation domain-binding protein-1 (Jab-1) [1]. MIF has been linked to various inflammatory diseases, such as rheumatoid arthritis and atherosclerosis [3].
The MIF homologue D-dopachrome tautomerase (EC:4.1.1.84) is involved in detoxification through the conversion of dopaminechrome (and possibly norepinephrinechrome), the toxic quinine product of the neurotransmitter dopamine (and norepinephrine), to an indole derivative that can serve as a precursor to neuromelanin [4, 5].
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Structural links
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Database links
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Pfam Clan: CL0082.8
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Publications
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1.
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Donn RP, Ray DW.
Macrophage migration inhibitory factor: molecular, cellular and genetic aspects of a key neuroendocrine molecule.
J. Endocrinol. 182 1-9 2004
[PubMed: 15225126]
http://dx.doi.org/10.1677/joe.0.1820001
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2.
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Van Molle W, Libert C.
How glucocorticoids control their own strength and the balance between pro- and anti-inflammatory mediators.
Eur. J. Immunol. 35 3396-9 2005
[PubMed: 16331703]
http://dx.doi.org/10.1002/eji.200535556
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3.
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Morand EF, Leech M, Bernhagen J.
MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis.
5 399-410 2006
[PubMed: 16628200]
http://dx.doi.org/10.1038/nrd2029
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4.
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Matsunaga J, Sinha D, Solano F, Santis C, Wistow G, Hearing V.
Macrophage migration inhibitory factor (MIF)--its role in catecholamine metabolism.
Cell. Mol. Biol. (Noisy-le-grand) 45 1035-40 1999
[PubMed: 10644007]
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5.
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Sugimoto H, Taniguchi M, Nakagawa A, Tanaka I, Suzuki M, Nishihira J.
Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 A resolution.
Biochemistry 38 3268-79 1999
[PubMed: 10079069]
http://dx.doi.org/10.1021/bi982184o
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Additional Reading
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Suzuki M, Takamura Y, Maeno M, Tochinai S, Iyaguchi D, Tanaka I, Nishihira J, Ishibashi T.
Xenopus laevis macrophage migration inhibitory factor is essential for axis formation and neural development.
J. Biol. Chem. 279 2004 21406-14
[PubMed: 15024012]
http://dx.doi.org/10.1074/jbc.M311416200
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Golubkov PA, Johnson WH Jr, Czerwinski RM, Person MD, Wang SC, Whitman CP, Hackert ML.
Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate.
Bioorg. Chem. 34 2006 183-99
[PubMed: 16780921]
http://dx.doi.org/10.1016/j.bioorg.2006.05.001
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Lubetsky JB, Dios A, Han J, Aljabari B, Ruzsicska B, Mitchell R, Lolis E, Al-Abed Y.
The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents.
J. Biol. Chem. 277 2002 24976-82
[PubMed: 11997397]
http://dx.doi.org/10.1074/jbc.M203220200
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Crichlow GV, Cheng KF, Dabideen D, Ochani M, Aljabari B, Pavlov VA, Miller EJ, Lolis E, Al-Abed Y.
Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor.
J. Biol. Chem. 282 2007 23089-95
[PubMed: 17526494]
http://dx.doi.org/10.1074/jbc.M701825200
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Winner M, Meier J, Zierow S, Rendon BE, Crichlow GV, Riggs R, Bucala R, Leng L, Smith N, Lolis E, Trent JO, Mitchell RA.
A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells.
Cancer Res. 68 2008 7253-7
[PubMed: 18794110]
http://dx.doi.org/10.1158/0008-5472.CAN-07-6227
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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. 93 1996 5191-6
[PubMed: 8643551]
http://dx.doi.org/10.1073/pnas.93.11.5191
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InterPro 23.1
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