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P30904

- MIF_RAT

UniProt

P30904 - MIF_RAT

Protein

Macrophage migration inhibitory factor

Gene

Mif

Organism
Rattus norvegicus (Rat)
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.
    L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.

    Sites

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

    GO - Molecular functioni

    1. dopachrome isomerase activity Source: UniProtKB
    2. phenylpyruvate tautomerase activity Source: UniProtKB-EC
    3. protein complex binding Source: RGD

    GO - Biological processi

    1. aging Source: RGD
    2. brain development Source: RGD
    3. brain renin-angiotensin system Source: RGD
    4. cellular response to hydrogen peroxide Source: RGD
    5. cellular response to hypoxia Source: RGD
    6. drinking behavior Source: RGD
    7. hair follicle development Source: RGD
    8. inflammatory response Source: UniProtKB-KW
    9. innate immune response Source: UniProtKB-KW
    10. metabolic process Source: GOC
    11. positive regulation of acute inflammatory response Source: RGD
    12. positive regulation of axon regeneration Source: RGD
    13. positive regulation of glucose import Source: RGD
    14. positive regulation of glycolytic process Source: RGD
    15. positive regulation of immune response Source: RGD
    16. positive regulation of potassium ion transport Source: RGD
    17. positive regulation of smooth muscle cell migration Source: RGD
    18. response to drug Source: RGD
    19. response to estradiol Source: RGD
    20. response to glucocorticoid Source: RGD
    21. response to heat Source: RGD
    22. response to hormone Source: RGD
    23. response to inorganic substance Source: RGD
    24. response to insulin Source: RGD
    25. response to lipopolysaccharide Source: RGD
    26. response to mechanical stimulus Source: RGD
    27. response to menaquinone Source: RGD
    28. response to progesterone Source: RGD
    29. response to vitamin E Source: RGD
    30. skin development Source: RGD
    31. spermatogenesis Source: RGD
    32. wound healing Source: RGD

    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):
    Glutathione-binding 13 kDa protein
    L-dopachrome isomerase
    L-dopachrome tautomerase (EC:5.3.3.12)
    Phenylpyruvate tautomerase
    Gene namesi
    Name:Mif
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 20

    Organism-specific databases

    RGDi621163. Mif.

    Subcellular locationi

    Secreted By similarity. 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. cytoplasm Source: RGD
    2. extracellular space Source: RGD
    3. nucleus Source: RGD

    Keywords - Cellular componenti

    Cytoplasm, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 115114Macrophage migration inhibitory factorPRO_0000158068Add
    BLAST

    Amino acid modifications

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

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP30904.
    PRIDEiP30904.

    PTM databases

    PhosphoSiteiP30904.

    Expressioni

    Tissue specificityi

    Expressed in a wide variety of organs including brain, spleen, liver, muscle and kidney.

    Gene expression databases

    GenevestigatoriP30904.

    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 similarity.By similarity

    Protein-protein interaction databases

    IntActiP30904. 3 interactions.
    MINTiMINT-4590553.
    STRINGi10116.ENSRNOP00000008608.

    Structurei

    Secondary structure

    1
    115
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi3 – 86
    Helixi12 – 143
    Helixi19 – 3113
    Helixi35 – 373
    Beta strandi39 – 435
    Beta strandi58 – 669
    Helixi70 – 8819
    Helixi92 – 943
    Beta strandi95 – 1028

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FIMX-ray2.20A2-115[»]
    ProteinModelPortaliP30904.
    SMRiP30904. Positions 2-115.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP30904.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the MIF family.Curated

    Phylogenomic databases

    eggNOGiNOG08790.
    GeneTreeiENSGT00730000111101.
    HOGENOMiHOG000112325.
    HOVERGENiHBG003240.
    InParanoidiP30904.
    KOiK07253.
    OMAiKRSDFGW.
    OrthoDBiEOG7GXPDN.
    PhylomeDBiP30904.
    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.

    P30904-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPMFIVNTNV PRASVPEGFL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF    50
    SGTSDPCALC SLHSIGKIGG AQNRNYSKLL CGLLSDRLHI SPDRVYINYY 100
    DMNAANVGWN GSTFA 115
    Length:115
    Mass (Da):12,477
    Last modified:January 23, 2007 - v4
    Checksum:i8333F7B81B098445
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti51 – 511S → R in AAA62644. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S73424 mRNA. Translation: AAB32392.1.
    U20999 mRNA. Translation: AAA62644.1.
    U62326 mRNA. Translation: AAB04024.1.
    BC061545 mRNA. Translation: AAH61545.1.
    PIRiS27117.
    RefSeqiNP_112313.1. NM_031051.1.
    UniGeneiRn.2661.

    Genome annotation databases

    EnsembliENSRNOT00000008608; ENSRNOP00000008608; ENSRNOG00000006589.
    GeneIDi81683.
    KEGGirno:81683.
    UCSCiRGD:621163. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S73424 mRNA. Translation: AAB32392.1 .
    U20999 mRNA. Translation: AAA62644.1 .
    U62326 mRNA. Translation: AAB04024.1 .
    BC061545 mRNA. Translation: AAH61545.1 .
    PIRi S27117.
    RefSeqi NP_112313.1. NM_031051.1.
    UniGenei Rn.2661.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1FIM X-ray 2.20 A 2-115 [» ]
    ProteinModelPortali P30904.
    SMRi P30904. Positions 2-115.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P30904. 3 interactions.
    MINTi MINT-4590553.
    STRINGi 10116.ENSRNOP00000008608.

    PTM databases

    PhosphoSitei P30904.

    Proteomic databases

    PaxDbi P30904.
    PRIDEi P30904.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000008608 ; ENSRNOP00000008608 ; ENSRNOG00000006589 .
    GeneIDi 81683.
    KEGGi rno:81683.
    UCSCi RGD:621163. rat.

    Organism-specific databases

    CTDi 4282.
    RGDi 621163. Mif.

    Phylogenomic databases

    eggNOGi NOG08790.
    GeneTreei ENSGT00730000111101.
    HOGENOMi HOG000112325.
    HOVERGENi HBG003240.
    InParanoidi P30904.
    KOi K07253.
    OMAi KRSDFGW.
    OrthoDBi EOG7GXPDN.
    PhylomeDBi P30904.
    TreeFami TF313853.

    Miscellaneous databases

    EvolutionaryTracei P30904.
    NextBioi 615308.

    Gene expression databases

    Genevestigatori P30904.

    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. "Glutathione binding rat liver 13k protein is the homologue of the macrophage migration inhibitory factor."
      Sakai M., Nishihira J., Hibiya Y., Koyama Y., Nishi S.
      Biochem. Mol. Biol. Int. 33:439-446(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. Wen Y., Li G., Bekhor I.
      Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lens.
    3. Sleeman M.A., Huckle J.W., Robinson M., Jahoda C.A.B., Reynolds A.J., Whitehouse C.J.
      Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: PVG/C.
    4. "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].
      Tissue: Pituitary.
    5. "Rat liver protein linking chemical and immunological detoxification systems."
      Blocki F.A., Schlievert P.M., Wackett L.P.
      Nature 360:269-270(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-26.
    6. Lubec G., Diao W., Kang S.U.
      Submitted (JUL-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-12 AND 79-87, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: Sprague-Dawley.
      Tissue: Brain and Hippocampus.
    7. "Crystal structure of the macrophage migration inhibitory factor from rat liver."
      Suzuki M., Sugimoto H., Nakagawa A., Tanaka I., Nishihira J., Sakai M.
      Nat. Struct. Biol. 3:259-266(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
      Tissue: Liver.

    Entry informationi

    Entry nameiMIF_RAT
    AccessioniPrimary (citable) accession number: P30904
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 128 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

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

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3