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P34884

- MIF_MOUSE

UniProt

P34884 - MIF_MOUSE

Protein

Macrophage migration inhibitory factor

Gene

Mif

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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 By similarity.By similarity

    Catalytic activityi

    Keto-phenylpyruvate = enol-phenylpyruvate.1 Publication
    L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei2 – 21Proton acceptor; via imino nitrogen
    Binding sitei33 – 331Substrate
    Binding sitei65 – 651Substrate; via amide nitrogenBy similarity
    Binding sitei98 – 981Substrate

    GO - Molecular functioni

    1. chemoattractant activity Source: Ensembl
    2. cytokine activity Source: BHF-UCL
    3. dopachrome isomerase activity Source: UniProtKB
    4. phenylpyruvate tautomerase activity Source: MGI

    GO - Biological processi

    1. cell aging Source: MGI
    2. cell proliferation Source: Ensembl
    3. cell surface receptor signaling pathway Source: Ensembl
    4. DNA damage response, signal transduction by p53 class mediator Source: MGI
    5. inflammatory response Source: UniProtKB-KW
    6. innate immune response Source: UniProtKB-KW
    7. negative regulation of apoptotic process Source: BHF-UCL
    8. negative regulation of cell aging Source: Ensembl
    9. negative regulation of cell cycle arrest Source: Ensembl
    10. negative regulation of cellular protein metabolic process Source: BHF-UCL
    11. negative regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
    12. negative regulation of gene expression Source: Ensembl
    13. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
    14. negative regulation of mature B cell apoptotic process Source: BHF-UCL
    15. negative regulation of myeloid cell apoptotic process Source: BHF-UCL
    16. positive regulation of adaptive immune response Source: BHF-UCL
    17. positive regulation of arachidonic acid secretion Source: BHF-UCL
    18. positive regulation of B cell proliferation Source: Ensembl
    19. positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
    20. positive regulation of cytokine secretion Source: Ensembl
    21. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
    22. positive regulation of fibroblast proliferation Source: BHF-UCL
    23. positive regulation of lipopolysaccharide-mediated signaling pathway Source: BHF-UCL
    24. positive regulation of MAP kinase activity Source: BHF-UCL
    25. positive regulation of myeloid leukocyte cytokine production involved in immune response Source: BHF-UCL
    26. positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
    27. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
    28. positive regulation of prostaglandin secretion involved in immune response Source: BHF-UCL
    29. positive regulation of protein kinase A signaling Source: Ensembl
    30. positive regulation of protein phosphorylation Source: BHF-UCL
    31. prostaglandin biosynthetic process Source: Ensembl
    32. protein homotrimerization Source: Ensembl
    33. regulation of cell proliferation Source: MGI

    Keywords - Molecular functioni

    Cytokine, Isomerase

    Keywords - Biological processi

    Immunity, Inflammatory response, Innate immunity

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Macrophage migration inhibitory factor (EC:5.3.2.1)
    Short name:
    MIF
    Alternative name(s):
    Delayed early response protein 6
    Short name:
    DER6
    Glycosylation-inhibiting factor
    Short name:
    GIF
    L-dopachrome isomerase
    L-dopachrome tautomerase (EC:5.3.3.12)
    Phenylpyruvate tautomerase
    Gene namesi
    Name:Mif
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:96982. Mif.

    Subcellular locationi

    Secreted 2 Publications. Cytoplasm By similarity
    Note: Does not have a cleavable signal sequence and is secreted via a specialized, non-classical pathway. Secreted by macrophages upon stimulation by bacterial lipopolysaccharide (LPS), or by M.tuberculosis antigens By similarity.By similarity

    GO - Cellular componenti

    1. cell surface Source: Ensembl
    2. cytoplasm Source: UniProtKB-SubCell
    3. extracellular space Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2 – 21P → G: Loss of tautomerase activity, reduced activation of intracellular signaling pathways, and reduced interaction with CXCR2 and COPS5. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed3 Publications
    Chaini2 – 115114Macrophage migration inhibitory factorPRO_0000158066Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei78 – 781N6-acetyllysine; alternate1 Publication
    Modified residuei78 – 781N6-succinyllysine; alternate1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP34884.
    PaxDbiP34884.
    PRIDEiP34884.

    PTM databases

    PhosphoSiteiP34884.

    Expressioni

    Gene expression databases

    BgeeiP34884.
    CleanExiMM_MIF.
    GenevestigatoriP34884.

    Interactioni

    Subunit structurei

    Homotrimer. Interacts with BNIPL By similarity. Interacts with the CD74 extracellular domain. Interacts with COPS5 and with the CXCR2 extracellular domain.By similarity2 Publications

    Protein-protein interaction databases

    BioGridi201418. 1 interaction.
    IntActiP34884. 4 interactions.
    MINTiMINT-1869498.
    STRINGi10090.ENSMUSP00000041149.

    Structurei

    Secondary structure

    1
    115
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi3 – 108
    Helixi12 – 143
    Helixi19 – 3113
    Helixi35 – 373
    Beta strandi39 – 435
    Beta strandi47 – 504
    Beta strandi58 – 669
    Helixi70 – 8819
    Helixi92 – 943
    Beta strandi95 – 1017
    Helixi104 – 1063
    Beta strandi107 – 1093

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1MFFX-ray2.00A/B/C2-115[»]
    1MFIX-ray1.80A/B/C2-115[»]
    2GDGX-ray1.45A/B/C2-115[»]
    ProteinModelPortaliP34884.
    SMRiP34884. Positions 2-115.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP34884.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the MIF family.Curated

    Phylogenomic databases

    eggNOGiNOG08790.
    HOGENOMiHOG000112325.
    HOVERGENiHBG003240.
    InParanoidiP34884.
    KOiK07253.
    OMAiQLSSEIC.
    OrthoDBiEOG7GXPDN.
    PhylomeDBiP34884.
    TreeFamiTF313853.

    Family and domain databases

    InterProiIPR001398. Macrophage_inhib_fac.
    IPR019829. Macrophage_inhib_fac_CS.
    IPR014347. Tautomerase/MIF_sf.
    [Graphical view]
    PANTHERiPTHR11954. PTHR11954. 1 hit.
    PfamiPF01187. MIF. 1 hit.
    [Graphical view]
    ProDomiPD004816. Macrophage_inhib_fac. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SUPFAMiSSF55331. SSF55331. 1 hit.
    PROSITEiPS01158. MIF. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P34884-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPMFIVNTNV PRASVPEGFL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF    50
    SGTNDPCALC SLHSIGKIGG AQNRNYSKLL CGLLSDRLHI SPDRVYINYY 100
    DMNAANVGWN GSTFA 115
    Length:115
    Mass (Da):12,504
    Last modified:January 23, 2007 - v2
    Checksum:i92D207B81B149945
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z23048 mRNA. Translation: CAA80583.1.
    U19825 Genomic DNA. Translation: AAA91637.1.
    L10613 mRNA. Translation: AAA37693.1.
    U20156 Genomic DNA. Translation: AAA91638.1.
    L39357 Genomic DNA. Translation: AAA74321.1.
    BC024895 mRNA. Translation: AAH24895.1.
    BC086928 mRNA. Translation: AAH86928.1.
    L07607 mRNA. Translation: AAA37111.1.
    CCDSiCCDS23934.1.
    PIRiA44499.
    RefSeqiNP_034928.1. NM_010798.2.
    UniGeneiMm.2326.

    Genome annotation databases

    EnsembliENSMUST00000038169; ENSMUSP00000041149; ENSMUSG00000033307.
    GeneIDi17319.
    KEGGimmu:17319.
    UCSCiuc007ftc.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z23048 mRNA. Translation: CAA80583.1 .
    U19825 Genomic DNA. Translation: AAA91637.1 .
    L10613 mRNA. Translation: AAA37693.1 .
    U20156 Genomic DNA. Translation: AAA91638.1 .
    L39357 Genomic DNA. Translation: AAA74321.1 .
    BC024895 mRNA. Translation: AAH24895.1 .
    BC086928 mRNA. Translation: AAH86928.1 .
    L07607 mRNA. Translation: AAA37111.1 .
    CCDSi CCDS23934.1.
    PIRi A44499.
    RefSeqi NP_034928.1. NM_010798.2.
    UniGenei Mm.2326.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1MFF X-ray 2.00 A/B/C 2-115 [» ]
    1MFI X-ray 1.80 A/B/C 2-115 [» ]
    2GDG X-ray 1.45 A/B/C 2-115 [» ]
    ProteinModelPortali P34884.
    SMRi P34884. Positions 2-115.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201418. 1 interaction.
    IntActi P34884. 4 interactions.
    MINTi MINT-1869498.
    STRINGi 10090.ENSMUSP00000041149.

    Chemistry

    ChEMBLi CHEMBL1926491.

    PTM databases

    PhosphoSitei P34884.

    Proteomic databases

    MaxQBi P34884.
    PaxDbi P34884.
    PRIDEi P34884.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000038169 ; ENSMUSP00000041149 ; ENSMUSG00000033307 .
    GeneIDi 17319.
    KEGGi mmu:17319.
    UCSCi uc007ftc.1. mouse.

    Organism-specific databases

    CTDi 4282.
    MGIi MGI:96982. Mif.

    Phylogenomic databases

    eggNOGi NOG08790.
    HOGENOMi HOG000112325.
    HOVERGENi HBG003240.
    InParanoidi P34884.
    KOi K07253.
    OMAi QLSSEIC.
    OrthoDBi EOG7GXPDN.
    PhylomeDBi P34884.
    TreeFami TF313853.

    Miscellaneous databases

    EvolutionaryTracei P34884.
    NextBioi 291888.
    PROi P34884.
    SOURCEi Search...

    Gene expression databases

    Bgeei P34884.
    CleanExi MM_MIF.
    Genevestigatori P34884.

    Family and domain databases

    InterProi IPR001398. Macrophage_inhib_fac.
    IPR019829. Macrophage_inhib_fac_CS.
    IPR014347. Tautomerase/MIF_sf.
    [Graphical view ]
    PANTHERi PTHR11954. PTHR11954. 1 hit.
    Pfami PF01187. MIF. 1 hit.
    [Graphical view ]
    ProDomi PD004816. Macrophage_inhib_fac. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SUPFAMi SSF55331. SSF55331. 1 hit.
    PROSITEi PS01158. MIF. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia."
      Bernhagen J., Calandra T., Mitchell R.A., Martin S.B., Tracey K.J., Voelter W., Manogue K.R., Cerami A., Bucala R.
      Nature 365:756-759(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-28.
      Tissue: Pituitary.
    2. "Growth factor-induced delayed early response genes."
      Lanahan A.A., Williams J.B., Sanders L.K., Nathans D.
      Mol. Cell. Biol. 12:3919-3929(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
    3. "Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor."
      Mikayama T., Nakano T., Gomi H., Nakagawa Y., Liu Y.C., Iwamatsu A., Weiser W.Y., Ishizaka K., Sato M., Ishii Y.
      Proc. Natl. Acad. Sci. U.S.A. 90:10056-10060(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
    4. "Cloning and characterization of the gene for mouse macrophage migration inhibitory factor (MIF)."
      Mitchell R., Bacher M., Bernhagen J., Pushkarskaya T., Seldin M.F., Bucala R.
      J. Immunol. 154:3863-3870(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/Sv.
    5. "Structural characterization and chromosomal location of the mouse macrophage migration inhibitory factor gene and pseudogenes."
      Bozza M., Kolakowski L.F. Jr., Jenkins N.A., Gilbert D.J., Copeland N.G., David J.R., Gerard C.
      Genomics 27:412-419(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/Sv.
    6. "Genomic cloning of mouse MIF (macrophage inhibitory factor) and genetic mapping of the human and mouse expressed gene and nine mouse pseudogenes."
      Kozak C.A., Adamson M.C., Buckler C.E., Segovia L., Paralkar V., Wistow G.
      Genomics 27:405-411(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/Sv.
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Kidney and Mammary gland.
    8. Lubec G., Klug S.
      Submitted (MAR-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-12, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Hippocampus.
    9. "A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens."
      Wistow G.J., Shaughnessy M., Lee D.C., Hodin J., Zelenka P.S.
      Proc. Natl. Acad. Sci. U.S.A. 90:1272-1275(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-115.
      Tissue: Lens.
    10. "Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF)."
      Bernhagen J., Mitchell R.A., Calandra T., Voelter W., Cerami A., Bucala R.
      Biochemistry 33:14144-14155(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    11. "Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor."
      Crichlow G.V., Cheng K.F., Dabideen D., Ochani M., Aljabari B., Pavlov V.A., Miller E.J., Lolis E., Al-Abed Y.
      J. Biol. Chem. 282:23089-23095(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, ROLE OF TAUTOMERASE INHIBITORS IN IMPROVED SURVIVAL IN CASE OF SEPSIS.
    12. "A tautomerase-null macrophage migration-inhibitory factor (MIF) gene knock-in mouse model reveals that protein interactions and not enzymatic activity mediate MIF-dependent growth regulation."
      Fingerle-Rowson G., Kaleswarapu D.R., Schlander C., Kabgani N., Brocks T., Reinart N., Busch R., Schuetz A., Lue H., Du X., Liu A., Xiong H., Chen Y., Nemajerova A., Hallek M., Bernhagen J., Leng L., Bucala R.
      Mol. Cell. Biol. 29:1922-1932(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CD74; CXCR2 AND COPS5, CATALYTIC ACTIVITY, MUTAGENESIS OF PRO-2.
    13. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-78, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-78, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.
    14. "Crystal structure of macrophage migration inhibitory factor complexed with (E)-2-fluoro-p-hydroxycinnamate at 1.8 A resolution: implications for enzymatic catalysis and inhibition."
      Taylor A.B., Johnson W.H. Jr., Czerwinski R.M., Li H.S., Hackert M.L., Whitman C.P.
      Biochemistry 38:7444-7452(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
    15. "Mechanism of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor: properties of the P1G, P1A, Y95F, and N97A mutants."
      Stamps S.L., Taylor A.B., Wang S.C., Hackert M.L., Whitman C.P.
      Biochemistry 39:9671-9678(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), TAUTOMERASE ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE, MUTAGENESIS OF PRO-2.
    16. "Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate."
      Golubkov P.A., Johnson W.H. Jr., Czerwinski R.M., Person M.D., Wang S.C., Whitman C.P., Hackert M.L.
      Bioorg. Chem. 34:183-199(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH INHIBITOR, TAUTOMERASE ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT.

    Entry informationi

    Entry nameiMIF_MOUSE
    AccessioniPrimary (citable) accession number: P34884
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 134 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    MIF tautomerase inhibitors improve survival in case of sepsis.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3