Macrophage migration inhibitory factor
Encyclopedia
Macrophage migration inhibitory factor (MIF or MMIF) also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein
that in humans is encoded by the MIF gene
.
and a four-stranded beta sheet
. The monomers surround a central channel with 3-fold rotational symmetry
.
that can catalyze the conversion of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). MIF also contains a Cys-Ala-Leu-Cys catalytic site between residues 57 and 60 that appears to function as a disulfide
reductase
.
involved in cell-mediated immunity
, immunoregulation, and inflammation
. MIF plays a role in the regulation of macrophage
function in host defense through the suppression of anti-inflammatory effects of glucocorticoid
s. This lymphokine and the JAB1
protein form a complex in the cytosol
near the peripheral plasma membrane, which may indicate a role in integrin
signaling pathways.
It has also been shown to induce changes in the heart during sepsis
.
with:
(RA) severity.
Additionally, evidence suggests that there is a correlation between MIF production and metastatic potential in colorectal cancer
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the MIF gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Structure
Macrophage migration inhibitory factor assembles into a trimer composed of three identical subunits. Each of these monomers contain two antiparallel alpha helicesAlpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
and a four-stranded beta sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
. The monomers surround a central channel with 3-fold rotational symmetry
Rotational symmetry
Generally speaking, an object with rotational symmetry is an object that looks the same after a certain amount of rotation. An object may have more than one rotational symmetry; for instance, if reflections or turning it over are not counted, the triskelion appearing on the Isle of Man's flag has...
.
Enzymatic activity
MIF contains two motifs with catalytic activity. The first is a 27 amino acid motif located at the N-terminus functions as a phenylpyruvate tautomerasePhenylpyruvate tautomerase
In enzymology, a phenylpyruvate tautomerase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, keto-phenylpyruvate, and one product, enol-phenylpyruvate....
that can catalyze the conversion of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). MIF also contains a Cys-Ala-Leu-Cys catalytic site between residues 57 and 60 that appears to function as a disulfide
Disulfide
In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....
reductase
Reductase
-Examples:* 5-alpha reductase* Dihydrofolate reductase* HMG-CoA reductase* Methemoglobin reductase* Ribonucleotide reductase* Thioredoxin reductase* E. coli nitroreductase* Methylenetetrahydrofolate reductase...
.
Function
This gene encodes a lymphokineLymphokine
Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte. They are protein mediators typically produced by T cells to direct the immune system response by signalling between its cells...
involved in cell-mediated immunity
Cell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
, immunoregulation, and inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. MIF plays a role in the regulation of macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
function in host defense through the suppression of anti-inflammatory effects of glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
s. This lymphokine and the JAB1
COP9 constitutive photomorphogenic homolog subunit 5
COP9 constitutive photomorphogenic homolog subunit 5 , also known as COPS5 or Csn5, is a gene conserved from humans to Saccharomyces cerevisiae.-Interactions:...
protein form a complex in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
near the peripheral plasma membrane, which may indicate a role in integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
signaling pathways.
It has also been shown to induce changes in the heart during sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
.
Interactions
Macrophage migration inhibitory factor has been reported to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- BNIPLBNIPLBcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein is a protein that in humans is encoded by the BNIPL gene.-Interactions:BNIPL has been shown to interact with Macrophage migration inhibitory factor, GFER, CDC42, BCL2-like 1 and Bcl-2....
, - CD74CD74HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74 , is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide involved in the formation and transport of MHC class II protein...
, - COPS5COP9 constitutive photomorphogenic homolog subunit 5COP9 constitutive photomorphogenic homolog subunit 5 , also known as COPS5 or Csn5, is a gene conserved from humans to Saccharomyces cerevisiae.-Interactions:...
, - CXCR4CXCR4C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :...
.
Clinical significance
MIF is an inflammatory mediator associated with rheumatoid arthritisRheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
(RA) severity.
Additionally, evidence suggests that there is a correlation between MIF production and metastatic potential in colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
.