Macrophage migration inhibitory factor (MIF)
The protein contains 115 amino acids for an estimated molecular weight of 12476 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
(right-click above to access to more options from the contextual menu)
Biological Process
Carboxylic acid metabolic process
Cell aging
Cell population proliferation
Cell surface receptor signaling pathway
DNA damage response, signal transduction by p53 class mediator
Inflammatory response
Innate immune response
Interleukin-12-mediated signaling pathway
Leukocyte migration
Negative regulation of apoptotic process
Negative regulation of cell aging
Negative regulation of cell cycle arrest
Negative regulation of cell migration
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 macrophage chemotaxis
Negative regulation of mature B cell apoptotic process
Negative regulation of myeloid cell apoptotic process
Neutrophil degranulation
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 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
Positive regulation of tumor necrosis factor production
Prostaglandin biosynthetic process
Protein homotrimerization
Regulation of macrophage activation
The reference OMIM entry for this protein is 153620
Macrophage migration inhibitory factor; mif
Mmif
CLONING
Migration inhibitory factor for guinea pig macrophages was the first lymphokine to be discovered (Bloom and Bennett, 1966; David, 1966). Expression of MIF activity was found to correlate well with delayed hypersensitivity and cellular immunity in humans. MIF activity could be detected in the synovia of patients with rheumatoid arthritis. The expression of MIF at sites of inflammation suggested a role for the mediator in regulating the function of macrophages in host defense. Weiser et al. (1989) isolated a cDNA encoding human macrophage migration inhibitory factor. By Northern blot analysis, Paralkar and Wistow (1994) demonstrated a single size of MIF mRNA (about 800 nucleotides) in all human tissues examined. In contrast to previous reports, they found no evidence for multiple genes for MIF in the human genome.GENE STRUCTURE
Paralkar and Wistow (1994) showed that the MIF gene is remarkably small; it has 3 exons separated by introns of only 189 and 95 bp, and covers less than 1 kb. Kozak et al. (1995) found that the exon/intron structure of the mouse Mif gene resembles that of the human gene. Bozza et al. (1995) found that the mouse Mif gene spans less than 0.7 kb of chromosomal DNA and is composed of 3 exons. Esumi et al. (1998) presented evidence that the gene for D-dopachrome tautomerase (DDT; 602750) in human and mouse is identical in exon structure to MIF. Both genes have 2 introns that are located at equivalent positions, relative to a 2-fold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT. In addition to similarities in structure, the genes for DDT and MIF are closely linked on human chromosome 22 and mouse chromosome 10.GENE FUNCTION
Bernhagen et al. (1993) identified MIF as a major secreted protein released by anterior pituitary cells in culture and in vivo in response to stimulation with bacterial lipopolysaccharide. They concluded that it plays a central role in the toxic response to endotoxemia and possibly septic shock. Bucala (1996) reviewed studies that led to the discovery of a pituitary mediator that appeared to act as the counter-regulatory hormone for glucocorticoid action within the immune system. Isolated as a product of murine anterior pituitary cells, this peptide was sequenced and found to be the mouse homolog of MIF. MIF has the unique property of being released from macrophages and T cells in response to physiologic concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, antiinflammatory steroid concentrations. Once released, MIF 'overrides' or counter-regulates the immunosuppressive effects of steroids on immune cell activation and cytokine production. Bucala (1996) stated that because glucocorticoids are an integral part of the host's global response to infection or tissue invasion, the physiologic role of MIF is to act at an inflammatory site or lymph node to counterbalance the profound inhibitory effect of steroids on the immune response. Using full-length MIF as bait in a yeast 2-hybrid screen of a brain cDNA library, Kleemann et al. (2000) captured Jun activation domain-binding protein (JAB1, or COPS5; 604850) as an interacting partner of MIF. By coimmunoprecipitation and pull-down experiments, Kle ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 153620 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed