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P34884 (MIF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Macrophage migration inhibitory factor

Short name=MIF
EC=5.3.2.1
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 names
Name:Mif
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length115 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

Keto-phenylpyruvate = enol-phenylpyruvate. Ref.12

L-dopachrome = 5,6-dihydroxyindole-2-carboxylate. Ref.12

Subunit structure

Homotrimer. Interacts with BNIPL By similarity. Interacts with the CD74 extracellular domain. Interacts with COPS5 and with the CXCR2 extracellular domain. Ref.12 Ref.16

Subcellular location

Secreted. 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. Ref.3 Ref.11

Miscellaneous

MIF tautomerase inhibitors improve survival in case of sepsis.

Sequence similarities

Belongs to the MIF family.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasm
Secreted
   Molecular functionCytokine
Isomerase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator

Inferred from mutant phenotype PubMed 12878730. Source: MGI

cell aging

Inferred from mutant phenotype PubMed 12878730. Source: MGI

cell proliferation

Inferred from electronic annotation. Source: Ensembl

cell surface receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from direct assay PubMed 17045821. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from direct assay PubMed 17045821. Source: BHF-UCL

negative regulation of cell aging

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

negative regulation of cellular protein metabolic process

Inferred from direct assay PubMed 11756671. Source: BHF-UCL

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

negative regulation of mature B cell apoptotic process

Inferred from direct assay PubMed 18056708. Source: BHF-UCL

negative regulation of myeloid cell apoptotic process

Inferred from mutant phenotype PubMed 11756671. Source: BHF-UCL

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 10364264PubMed 17045821. Source: BHF-UCL

positive regulation of MAP kinase activity

Inferred from direct assay PubMed 10364264. Source: BHF-UCL

positive regulation of adaptive immune response

Non-traceable author statement PubMed 18056708. Source: BHF-UCL

positive regulation of arachidonic acid secretion

Inferred from direct assay PubMed 10364264. Source: BHF-UCL

positive regulation of chemokine (C-X-C motif) ligand 2 production

Inferred from direct assay PubMed 18056708. Source: BHF-UCL

positive regulation of cytokine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of fibroblast proliferation

Inferred from direct assay PubMed 10364264. Source: BHF-UCL

positive regulation of lipopolysaccharide-mediated signaling pathway

Inferred from mutant phenotype PubMed 11756671. Source: BHF-UCL

positive regulation of myeloid leukocyte cytokine production involved in immune response

Inferred from mutant phenotype PubMed 11756671. Source: BHF-UCL

positive regulation of peptidyl-serine phosphorylation

Inferred from direct assay PubMed 17045821. Source: BHF-UCL

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 17045821. Source: BHF-UCL

positive regulation of prostaglandin secretion involved in immune response

Inferred from mutant phenotype PubMed 11756671. Source: BHF-UCL

positive regulation of protein kinase A signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 10364264. Source: BHF-UCL

prostaglandin biosynthetic process

Inferred from electronic annotation. Source: Ensembl

protein homotrimerization

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from mutant phenotype PubMed 12878730. Source: MGI

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from direct assay PubMed 11756671. Source: BHF-UCL

   Molecular_functionchemoattractant activity

Inferred from electronic annotation. Source: Ensembl

cytokine activity

Inferred from direct assay PubMed 10364264PubMed 17045821. Source: BHF-UCL

dopachrome isomerase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phenylpyruvate tautomerase activity

Inferred from mutant phenotype PubMed 16285950. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.1 Ref.8 Ref.15
Chain2 – 115114Macrophage migration inhibitory factor
PRO_0000158066

Sites

Active site21Proton acceptor; via imino nitrogen
Binding site331Substrate
Binding site651Substrate; via amide nitrogen By similarity
Binding site981Substrate

Amino acid modifications

Modified residue781N6-acetyllysine; alternate Ref.13
Modified residue781N6-succinyllysine; alternate Ref.13

Experimental info

Mutagenesis21P → G: Loss of tautomerase activity, reduced activation of intracellular signaling pathways, and reduced interaction with CXCR2 and COPS5. Ref.12 Ref.15

Secondary structure

....................... 115
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P34884 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 92D207B81B149945

FASTA11512,504
        10         20         30         40         50         60 
MPMFIVNTNV PRASVPEGFL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF SGTNDPCALC 

        70         80         90        100        110 
SLHSIGKIGG AQNRNYSKLL CGLLSDRLHI SPDRVYINYY DMNAANVGWN GSTFA 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS23934.1.
PIRA44499.
RefSeqNP_034928.1. NM_010798.2.
UniGeneMm.2326.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MFFX-ray2.00A/B/C2-115[»]
1MFIX-ray1.80A/B/C2-115[»]
2GDGX-ray1.45A/B/C2-115[»]
ProteinModelPortalP34884.
SMRP34884. Positions 2-115.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201418. 1 interaction.
IntActP34884. 4 interactions.
MINTMINT-1869498.
STRING10090.ENSMUSP00000041149.

Chemistry

ChEMBLCHEMBL1926491.

PTM databases

PhosphoSiteP34884.

Proteomic databases

MaxQBP34884.
PaxDbP34884.
PRIDEP34884.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000038169; ENSMUSP00000041149; ENSMUSG00000033307.
GeneID17319.
KEGGmmu:17319.
UCSCuc007ftc.1. mouse.

Organism-specific databases

CTD4282.
MGIMGI:96982. Mif.

Phylogenomic databases

eggNOGNOG08790.
HOGENOMHOG000112325.
HOVERGENHBG003240.
InParanoidP34884.
KOK07253.
OMAQLSSEIC.
OrthoDBEOG7GXPDN.
PhylomeDBP34884.
TreeFamTF313853.

Gene expression databases

BgeeP34884.
CleanExMM_MIF.
GenevestigatorP34884.

Family and domain databases

InterProIPR001398. Macrophage_inhib_fac.
IPR019829. Macrophage_inhib_fac_CS.
IPR014347. Tautomerase/MIF_sf.
[Graphical view]
PANTHERPTHR11954. PTHR11954. 1 hit.
PfamPF01187. MIF. 1 hit.
[Graphical view]
ProDomPD004816. Macrophage_inhib_fac. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF55331. SSF55331. 1 hit.
PROSITEPS01158. MIF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP34884.
NextBio291888.
PROP34884.
SOURCESearch...

Entry information

Entry nameMIF_MOUSE
AccessionPrimary (citable) accession number: P34884
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot