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FLASH GENE
Symbol MIF contributors: mct - updated : 21-01-2015
HGNC name macrophage migration inhibitory factor (glycosylation-inhibiting factor)
HGNC id 7097
Location 22q11.23      Physical location : 24.236.564 - 24.237.409
Synonym name
  • glycosylation-inhibiting factor
  • phenylpyruvate tautomerase
  • L-dopachrome tautomerase
  • glycosylation-inhibiting factor
  • Synonym symbol(s) GIF, GLIF, MMIF
    EC.number 5.3.3.12, 5.3.2.1
    DNA
    TYPE functioning gene
    STRUCTURE 0.85 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    RTDR1 22q11.2 rhabdoid tumor deletion region gene 1 GNAZ 22q11.22 guanine nucleotide binding protein (G protein), alpha z polypeptide RAB36 22q11.2 RAB36, member RAS oncogene family BCR 22q11.23 breakpoint cluster region FBXW3 22q11 F-box and WD-40 domain protein 3 LOC343851 22q11.23 similar to hypothetical protein FLJ31547 FLJ31568 22q11.23 hypothetical protein FLJ31568 LOC388882 22 hypothetical gene supported by BC036910 LOC388883 22 similar to Gag-Pro-Pol protein IGLL1 22q11.22 immunoglobulin lambda-like polypeptide 1 LOC391321 22 similar to Rhabdoid tumor deletion region protein 1 LOC51233 22q11.2 hypothetical protein LOC51233 LOC388884 22 similar to Immunoglobulin lambda-like polypeptide 1 precursor (Immunoglobulin-related 14.1 protein) (Immunoglobulin omega polypeptide) (Lambda 5) (CD179b antigen) ASLL 22q11.22 argininosuccinate lyase-like Rgr 22q11.23 Ral-GDS related protein Rgr ZNF70 22q11.22 zinc finger protein 70 (Cos17) VPREB3 22q11.2 pre-B lymphocyte gene 3 FLJ36561 22q11.23 hypothetical protein FLJ36561 MMP11 22q11.22 matrix metalloproteinase 11 (stromelysin 3) SMARCB1 22q11.23 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 FLJ43842 22q11.23 FLJ43842 protein SLC2A11 22q11.2 solute carrier family 2 (facilitated glucose transporter), member 11 MIF 22q11.22 macrophage migration inhibitory factor (glycosylation-inhibiting factor) LOC284890 22q11.23 similar to lymphocyte activation-associated protein; kelch (Drosophila)-like 5 DDT 22q11.23 D-dopachrome tautomerase GSTT2 22q11.23 glutathione S-transferase theta 2 HS322B1A 22q12 hypothetical protein HS322B1A LOC391322 22 similar to D-dopachrome tautomerase (Phenylpyruvate tautomerase II) GSTT1 22q11.23 glutathione S-transferase theta 1 LOC343854 22q11.23 similar to RIKEN cDNA 4930583C14 CABIN1 22q11.2-q12.3 similar to RIKEN cDNA 4930583C14 BK65A6.2 GGTLA1 22q11.2 gamma-glutamyltransferase-like activity 1 LOC339661 22q11.23 similar to Gamma-glutamyltransferase-like protein 4 DKFZP434P211 22q11.22 POM121-like protein LOC388885 22 LOC388885 KIAA0376 22q11.2-q12.3 LOC388885 ADORA2A 22q11.22 adenosine A2a receptor UPB1 22q11.2 ureidopropionase, beta MGC1842 22q11.2 hypothetical protein MGC1842 SNRPD3 22q11.21 small nuclear ribonucleoprotein D3 polypeptide 18kDa GGT1 22q11.23 gamma-glutamyltransferase 1 LOC388886 22 similar to hypothetical protein LOC192734
    regionally located closely linked to the related gene DDT
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 561 - 115 - 2000 11089976
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    endocrinebraindiencephalonpituitary  
    Endocrinepancreas   highly
     parathyroid   highly
    Hearing/Equilibriumearinnercochlea   Mus musculusFetal
    Respiratorylung   highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Connective    
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumcochlea cell Mus musculusFetal
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C-terminal region highly conserved and participating in several intramolecular interactions that suggest a role in modulating the stability and biochemical activity of MIF
  • mono polymer homomer , trimer
    HOMOLOGY
    Homologene
    FAMILY
  • MIF family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text near the plasma membrane
    basic FUNCTION
  • lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation
  • playing a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids
  • also acting as a phenylpyruvate tautomerase, and additional role in integrin signaling pathways
  • catalyzes the tautomerization of d-dopachrome methyl ester
  • involved in the regulation and having different roles in the reparative, reproductive and inflammatory-like processes occuring in endometrium during every menstrual cycle
  • plays an important role in acute and chronic inflammatory diseases such as septic shock, rheumatoid arthritis and colitis
  • essential and crucial role in cell proliferation and the cell cycle
  • may regulate the pro-apoptotic activity of BCL2L11 and inhibit the release of cytochrome c from mitochondria
  • plays a complex role in malarial pathogenesis
  • chemokine-like inflammatory mediator that triggers leukocyte recruitment by binding to CXCR2 and CXCR4
  • proinflammatory cytokine secreted by activated T cells and macrophages that has antiapoptotic, proproliferative, and chemotactic effects
  • potential skeletal muscle cytokine with probable functions beyond inflammatory pathology in the complex regenerative response to muscle fiber damage
  • with SOD2 appear to be early predictors for survival in septic patients
  • key proinflammatory mediator, which plays a pivotal role in inflammatory and immune diseases
  • important factor responsible for early polymorphonuclear cell activation and can be a target of immunomodulation after injury
  • promotes leukocyte recruitment to sites of inflammation
  • MIF and CD74 play previously unappreciated roles in CCL2-induced macrophage adhesion and migration, and they indicate that MIF and CD74 mediate this effect via both common and independent mechanisms
  • MIF and its receptor, CD74, are involved in regulating the migration of human mesenchymal stem cells (MSCs
  • is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear
  • CELLULAR PROCESS cell cycle, progression
    PHYSIOLOGICAL PROCESS immunity/defense
    text modulating the cell-cycle through inhibiting COPS5 and stimulus-enhanced AP-1(JUN) activity through the suppression of antiinflammatory effects of glucocorticoids
    PATHWAY
    metabolism
    signaling
    involved in mitogenic response and the control of cell cycle progression
    a component
  • complexing with JAB1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • modulating AP-1 and COPS5 activity
  • BNIPL
  • ligand of CXCR2, CXCR4, CD74 (contributed to atherogenic recruitment via CXCR2 and CD74)
  • interacting with CXCR4 and CD74 (CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling)
  • USO1 is an intracellular binding partner for MIF (MIF interacts with USO1 in the cytoplasm and the stimulated secretion of MIF results in the accumulation of both proteins in supernatants, which is consistent with MIF release from cells in conjunction with USO1)
  • ARRB1 plays a central role in coupling MIF endocytosis to sustained ERK activation
  • thrombin (thrombin binding region in the sixth EGF like repeat)THBD and ICAM1 were induced with MIF addition in a dose-dependent and time-dependent manner
  • MIF inhibits the migration of cartilage end plate-derived stem cells by reacting with CD74
  • presence of CD74 on statoacoustic ganglion (SAG) neurons supports the existence of a signaling pathway by which MIF influences SAG survival and outgrowth
  • MIF promotes the migration of B cells through a ZAP70-dependent pathway mediated by cooperative engagement of CXCR4 and CD74
  • on epithelial tumor cells promotes MIF binding and MIF-mediated cell migration
  • MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer
    tumoral     --over  
    in primary non-invasive breast cancer cell
    constitutional     --over  
    in endothelial cells, smooth muscle cells (SMCs) and macrophages during the development of atherosclerotic lesions
    tumoral     --over  
    CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis
    Susceptibility
  • to systemic juvenile rheumatoid arthritis
  • to development of duodenal ulcers
  • Variant & Polymorphism insertion/deletion , other
  • polymorphisms associated to systemic juvenile rheumatoid arthritis
  • tetranucleotide repeat polymorphism of MIF gene promoter might be associated with the development of duodenal ulcers
  • Candidate gene could represent a candidate gene for autism spectrum disorder
    Marker
    Therapy target
  • targeting MIF, it might therefore be possible to achieve therapeutic regression and stabilization of advanced atherosclerotic lesions
  • therapeutic target to treat non-insulin-dependent diabetes mellitus
  • viable therapeutic target for treating inflammatory diseases and neoplasia
  • SystemTypeDisorderPubmed
    diabete  
    ANIMAL & CELL MODELS
  • Mif knockout mice are hearing impaired with altered innervation to the organ of Corti, as well as fewer sensory hair cells