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Protein

Macrophage migration inhibitory factor

Gene

Mif

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Active sitei2Proton acceptor; via imino nitrogen1
Binding sitei33Substrate1
Binding sitei65Substrate; via amide nitrogenBy similarity1
Binding sitei98Substrate1

GO - Molecular functioni

  • chemoattractant activity Source: MGI
  • cytokine activity Source: BHF-UCL
  • cytokine receptor binding Source: MGI
  • dopachrome isomerase activity Source: UniProtKB
  • phenylpyruvate tautomerase activity Source: MGI
  • receptor binding Source: MGI

GO - Biological processi

  • carboxylic acid metabolic process Source: MGI
  • cell aging Source: MGI
  • cell proliferation Source: MGI
  • cell surface receptor signaling pathway Source: MGI
  • DNA damage response, signal transduction by p53 class mediator Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: BHF-UCL
  • negative regulation of cell aging Source: MGI
  • negative regulation of cell cycle arrest Source: MGI
  • negative regulation of cellular protein metabolic process Source: BHF-UCL
  • negative regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
  • negative regulation of gene expression Source: MGI
  • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
  • negative regulation of mature B cell apoptotic process Source: BHF-UCL
  • negative regulation of myeloid cell apoptotic process Source: BHF-UCL
  • positive regulation of adaptive immune response Source: BHF-UCL
  • positive regulation of arachidonic acid secretion Source: BHF-UCL
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
  • positive regulation of cytokine secretion Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • positive regulation of fibroblast proliferation Source: BHF-UCL
  • positive regulation of lipopolysaccharide-mediated signaling pathway Source: BHF-UCL
  • positive regulation of MAP kinase activity Source: BHF-UCL
  • positive regulation of myeloid leukocyte cytokine production involved in immune response Source: BHF-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  • positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  • positive regulation of phosphorylation Source: MGI
  • positive regulation of prostaglandin secretion involved in immune response Source: BHF-UCL
  • positive regulation of protein kinase A signaling Source: MGI
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • prostaglandin biosynthetic process Source: MGI
  • protein homotrimerization Source: MGI
  • regulation of cell proliferation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Isomerase

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

BRENDAi5.3.2.1. 3474.
ReactomeiR-MMU-202733. Cell surface interactions at the vascular wall.
R-MMU-6798695. Neutrophil degranulation.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96982. Mif.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: MGI
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • extracellular region Source: MGI
  • extracellular space Source: BHF-UCL
  • myelin sheath Source: UniProtKB
  • nucleoplasm Source: MGI
  • vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2P → G: Loss of tautomerase activity, reduced activation of intracellular signaling pathways, and reduced interaction with CXCR2 and COPS5. 2 Publications1

Chemistry databases

ChEMBLiCHEMBL1926491.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved3 Publications
ChainiPRO_00001580662 – 115Macrophage migration inhibitory factorAdd BLAST114

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78N6-acetyllysine; alternateCombined sources1
Modified residuei78N6-succinyllysine; alternateCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP34884.
PaxDbiP34884.
PeptideAtlasiP34884.
PRIDEiP34884.
TopDownProteomicsiP34884.

PTM databases

iPTMnetiP34884.
PhosphoSitePlusiP34884.

Expressioni

Gene expression databases

BgeeiENSMUSG00000033307.
CleanExiMM_MIF.
ExpressionAtlasiP34884. baseline and differential.
GenevisibleiP34884. MM.

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

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • cytokine receptor binding Source: MGI
  • receptor binding Source: MGI

Protein-protein interaction databases

BioGridi201418. 1 interactor.
IntActiP34884. 4 interactors.
MINTiMINT-1869498.
STRINGi10090.ENSMUSP00000041149.

Chemistry databases

BindingDBiP34884.

Structurei

Secondary structure

1115
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 10Combined sources8
Helixi12 – 14Combined sources3
Helixi19 – 31Combined sources13
Helixi35 – 37Combined sources3
Beta strandi39 – 43Combined sources5
Beta strandi47 – 50Combined sources4
Beta strandi58 – 66Combined sources9
Helixi70 – 88Combined sources19
Helixi92 – 94Combined sources3
Beta strandi95 – 101Combined sources7
Helixi104 – 106Combined sources3
Beta strandi107 – 109Combined sources3

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP34884.

Family & Domainsi

Sequence similaritiesi

Belongs to the MIF family.Curated

Phylogenomic databases

eggNOGiKOG1759. Eukaryota.
ENOG41122MF. LUCA.
GeneTreeiENSGT00840000129866.
HOGENOMiHOG000112325.
HOVERGENiHBG003240.
InParanoidiP34884.
KOiK07253.
OMAiMGKPAQY.
OrthoDBiEOG091G0ZNJ.
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi201418. 1 interactor.
IntActiP34884. 4 interactors.
MINTiMINT-1869498.
STRINGi10090.ENSMUSP00000041149.

Chemistry databases

BindingDBiP34884.
ChEMBLiCHEMBL1926491.

PTM databases

iPTMnetiP34884.
PhosphoSitePlusiP34884.

Proteomic databases

EPDiP34884.
PaxDbiP34884.
PeptideAtlasiP34884.
PRIDEiP34884.
TopDownProteomicsiP34884.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4282.
MGIiMGI:96982. Mif.

Phylogenomic databases

eggNOGiKOG1759. Eukaryota.
ENOG41122MF. LUCA.
GeneTreeiENSGT00840000129866.
HOGENOMiHOG000112325.
HOVERGENiHBG003240.
InParanoidiP34884.
KOiK07253.
OMAiMGKPAQY.
OrthoDBiEOG091G0ZNJ.
PhylomeDBiP34884.
TreeFamiTF313853.

Enzyme and pathway databases

BRENDAi5.3.2.1. 3474.
ReactomeiR-MMU-202733. Cell surface interactions at the vascular wall.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiP34884.
PROiP34884.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000033307.
CleanExiMM_MIF.
ExpressionAtlasiP34884. baseline and differential.
GenevisibleiP34884. MM.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 156 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.