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P34884

- MIF_MOUSE

UniProt

P34884 - MIF_MOUSE

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Protein

Macrophage migration inhibitory factor

Gene

Mif

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

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
Complete GO annotation...

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-KW
  3. extracellular space Source: BHF-UCL
  4. extracellular vesicular exosome Source: Ensembl
Complete GO annotation...

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.
ExpressionAtlasiP34884. baseline and differential.
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

        10         20         30         40         50
MPMFIVNTNV PRASVPEGFL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF
60 70 80 90 100
SGTNDPCALC SLHSIGKIGG AQNRNYSKLL CGLLSDRLHI SPDRVYINYY
110
DMNAANVGWN GSTFA
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.
ExpressionAtlasi P34884. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 135 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