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Protein

Macrophage migration inhibitory factor

Gene

MIF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.3 Publications

Miscellaneous

Serum levels of MIF are elevated in patients with severe sepsis or septic shock. High levels of MIF are correlated with low survival. Drugs that inhibit tautomerase activity protect against death due to sepsis.

Catalytic activityi

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

Kineticsi

  1. KM=249 µM for phenylpyruvate1 Publication
  2. KM=168 µM for p-hydroxyphenylpyruvate1 Publication
  1. Vmax=2113 µmol/min/mg enzyme toward phenylpyruvate1 Publication
  2. Vmax=524 µmol/min/mg enzyme toward p-hydroxyphenylpyruvate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2Proton acceptor; via imino nitrogen1
Binding sitei33Substrate1
Binding sitei65Substrate; via amide nitrogen1
Binding sitei98Substrate1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine, Isomerase
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

BRENDAi5.3.2.1 2681
5.3.3.12 2681
ReactomeiR-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-6798695 Neutrophil degranulation
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
SIGNORiP14174

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage migration inhibitory factor (EC:5.3.2.1)
Short name:
MIF
Alternative name(s):
Glycosylation-inhibiting factor
Short name:
GIF
L-dopachrome isomerase
L-dopachrome tautomerase (EC:5.3.3.12)
Phenylpyruvate tautomerase
Gene namesi
Name:MIF
Synonyms:GLIF, MMIF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000240972.1
HGNCiHGNC:7097 MIF
MIMi153620 gene
neXtProtiNX_P14174

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Involvement in diseasei

Rheumatoid arthritis systemic juvenile (RASJ)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.Curated
Disease descriptionAn inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.
See also OMIM:604302

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi111N → C: Causes formation of interchain disulfide bonds with Cys-81 from another subunit. 1 Publication1

Organism-specific databases

DisGeNETi4282
MalaCardsiMIF
MIMi604302 phenotype
OpenTargetsiENSG00000240972
Orphaneti85414 Systemic-onset juvenile idiopathic arthritis
PharmGKBiPA30819

Chemistry databases

ChEMBLiCHEMBL2085
DrugBankiDB07718 3-(4-HYDROXY-PHENYL)PYRUVIC ACID
DB08334 3-FLUORO-4-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIME
DB08333 4-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIME
DB02728 7-Hydroxy-2-Oxo-Chromene-3-Carboxylic Acid Ethyl Ester
DB04272 Citric Acid

Polymorphism and mutation databases

DMDMi1170955

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00001580622 – 115Macrophage migration inhibitory factorAdd BLAST114

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78N6-acetyllysine; alternateCombined sources1
Modified residuei78N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP14174
MaxQBiP14174
PaxDbiP14174
PeptideAtlasiP14174
PRIDEiP14174
ProteomicsDBi53030
TopDownProteomicsiP14174

2D gel databases

SWISS-2DPAGEiP14174

PTM databases

iPTMnetiP14174
PhosphoSitePlusiP14174
SwissPalmiP14174

Expressioni

Inductioni

Up-regulated in concanavalin-A-treated lymphocytes. Up-regulated in macrophages upon exposure to M.tuberculosis antigens.2 Publications

Gene expression databases

BgeeiENSG00000240972 Expressed in 89 organ(s), highest expression level in left adrenal gland
CleanExiHS_MIF
ExpressionAtlasiP14174 baseline and differential
GenevisibleiP14174 HS

Organism-specific databases

HPAiCAB005284
HPA003868

Interactioni

Subunit structurei

Homotrimer. Interacts with CXCR2 extracellular domain (By similarity). Interacts with the CD74 extracellular domain, COPS5 and BNIPL.By similarity8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110428, 62 interactors
DIPiDIP-31137N
IntActiP14174, 23 interactors
MINTiP14174
STRINGi9606.ENSP00000215754

Chemistry databases

BindingDBiP14174

Structurei

Secondary structure

1115
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP14174
SMRiP14174
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14174

Family & Domainsi

Sequence similaritiesi

Belongs to the MIF family.Curated

Phylogenomic databases

eggNOGiKOG1759 Eukaryota
ENOG41122MF LUCA
GeneTreeiENSGT00910000144267
HOGENOMiHOG000112325
HOVERGENiHBG003240
InParanoidiP14174
KOiK07253
OMAiPDRIYIN
OrthoDBiEOG091G0ZNJ
PhylomeDBiP14174
TreeFamiTF313853

Family and domain databases

Gene3Di3.30.429.10, 1 hit
InterProiView protein in InterPro
IPR001398 Macrophage_inhib_fac
IPR019829 Macrophage_inhib_fac_CS
IPR014347 Tautomerase/MIF_sf
PANTHERiPTHR11954 PTHR11954, 1 hit
PfamiView protein in Pfam
PF01187 MIF, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD004816 Macrophage_inhib_fac, 1 hit
SUPFAMiSSF55331 SSF55331, 1 hit
PROSITEiView protein in PROSITE
PS01158 MIF, 1 hit

Sequencei

Sequence statusi: Complete.

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

P14174-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPMFIVNTNV PRASVPDGFL SELTQQLAQA TGKPPQYIAV HVVPDQLMAF
60 70 80 90 100
GGSSEPCALC SLHSIGKIGG AQNRSYSKLL CGLLAERLRI SPDRVYINYY
110
DMNAANVGWN NSTFA
Length:115
Mass (Da):12,476
Last modified:January 23, 2007 - v4
Checksum:i56D51107C05286B2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57 – 59CAL → WAF in ABQ95571 (Ref. 6) Curated3
Sequence conflicti67K → R in CAG46452 (Ref. 9) Curated1
Sequence conflicti79L → Q in CAG46452 (Ref. 9) Curated1
Sequence conflicti81C → F in ABQ95571 (Ref. 6) Curated1
Sequence conflicti106N → S in AAA36315 (PubMed:2552447).Curated1
Sequence conflicti113T → P in ABQ95571 (Ref. 6) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25639 mRNA Translation: AAA36315.1
L10612 mRNA Translation: AAA35892.1
Z23063 mRNA Translation: CAA80598.1
L19686 Genomic DNA Translation: AAA21814.1
AF469046 mRNA Translation: AAL78635.1
EF611126 mRNA Translation: ABQ95571.1
CR456520 mRNA Translation: CAG30406.1
AK311929 mRNA Translation: BAG34870.1
CR407644 mRNA Translation: CAG28572.1
CR541651 mRNA Translation: CAG46452.1
BT007148 mRNA Translation: AAP35812.1
DQ307455 Genomic DNA Translation: ABB96245.1
CH471095 Genomic DNA Translation: EAW59620.1
BC000447 mRNA Translation: AAH00447.1
BC007676 mRNA Translation: AAH07676.1
BC008914 mRNA Translation: AAH08914.1
BC013976 mRNA Translation: AAH13976.1
BC022414 mRNA Translation: AAH22414.1
BC053376 mRNA Translation: AAH53376.1
M95775 mRNA Translation: AAA36179.1
CCDSiCCDS13819.1
PIRiA48793
RefSeqiNP_002406.1, NM_002415.1
UniGeneiHs.407995

Genome annotation databases

EnsembliENST00000215754; ENSP00000215754; ENSG00000240972
ENST00000613839; ENSP00000482779; ENSG00000276701
GeneIDi4282
KEGGihsa:4282
UCSCiuc002zyr.2 human

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25639 mRNA Translation: AAA36315.1
L10612 mRNA Translation: AAA35892.1
Z23063 mRNA Translation: CAA80598.1
L19686 Genomic DNA Translation: AAA21814.1
AF469046 mRNA Translation: AAL78635.1
EF611126 mRNA Translation: ABQ95571.1
CR456520 mRNA Translation: CAG30406.1
AK311929 mRNA Translation: BAG34870.1
CR407644 mRNA Translation: CAG28572.1
CR541651 mRNA Translation: CAG46452.1
BT007148 mRNA Translation: AAP35812.1
DQ307455 Genomic DNA Translation: ABB96245.1
CH471095 Genomic DNA Translation: EAW59620.1
BC000447 mRNA Translation: AAH00447.1
BC007676 mRNA Translation: AAH07676.1
BC008914 mRNA Translation: AAH08914.1
BC013976 mRNA Translation: AAH13976.1
BC022414 mRNA Translation: AAH22414.1
BC053376 mRNA Translation: AAH53376.1
M95775 mRNA Translation: AAA36179.1
CCDSiCCDS13819.1
PIRiA48793
RefSeqiNP_002406.1, NM_002415.1
UniGeneiHs.407995

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CA7X-ray2.50A/B/C2-115[»]
1CGQX-ray2.00A/B/C2-115[»]
1GCZX-ray1.90A/B/C2-115[»]
1GD0X-ray1.50A/B/C2-115[»]
1GIFX-ray1.90A/B/C1-115[»]
1LJTX-ray2.00A/B/C2-115[»]
1MIFX-ray2.60A/B/C1-115[»]
1P1GX-ray2.50A/B/C2-115[»]
2OOHX-ray1.85A/B/C2-115[»]
2OOWX-ray1.75A/B/C2-115[»]
2OOZX-ray1.80A/B/C2-115[»]
3B9SX-ray1.80A/B/C2-115[»]
3CE4X-ray1.55A/B/C2-115[»]
3DJHX-ray1.25A/B/C2-115[»]
3DJIX-ray1.95A/B/C/D/E/F2-115[»]
3HOFX-ray1.90A/B/C1-115[»]
3IJGX-ray1.70A/B/C2-115[»]
3IJJX-ray1.25A/B/C2-115[»]
3JSFX-ray1.93A/B/C2-115[»]
3JSGX-ray1.58A/B/C2-115[»]
3JTUX-ray1.86A/B/C2-115[»]
3L5PX-ray1.80A/B/C2-115[»]
3L5RX-ray1.94A/B/C2-115[»]
3L5SX-ray1.86A/B/C2-115[»]
3L5TX-ray1.86A/B/C2-115[»]
3L5UX-ray1.90A/B/C2-115[»]
3L5VX-ray1.70A/B/C2-115[»]
3SMBX-ray1.60A/B/C2-115[»]
3SMCX-ray1.80A/B/C2-115[»]
3U18X-ray1.90A/B/C2-115[»]
3WNRX-ray2.01A/B/C2-115[»]
3WNSX-ray1.66A/B/C2-115[»]
3WNTX-ray2.07A/B/C2-115[»]
4ETGX-ray1.61A/B/C2-115[»]
4EUIX-ray1.70A/B/C2-115[»]
4EVGX-ray1.70A/B/C2-115[»]
4F2KX-ray1.53A/B/C2-115[»]
4GRNX-ray1.25A/B/C2-115[»]
4GROX-ray2.00A/B/C/D/E/F/G/H2-115[»]
4GRPX-ray1.27A/B/C2-115[»]
4GRQX-ray1.65A/B/C2-115[»]
4GRRX-ray1.47A/B/C3-115[»]
4GRUX-ray1.92A/B/C2-115[»]
4GUMX-ray2.33A/B/C/D/E/F/G/H/I2-115[»]
4K9GX-ray1.55A/B/C2-115[»]
4OSFX-ray1.62A/B/C2-115[»]
4OYQX-ray1.70A/B/C2-115[»]
4P01X-ray2.07A/B/C2-115[»]
4P0HX-ray1.93A/B/C2-115[»]
4PKKX-ray1.78A/B/C2-115[»]
4PKZX-ray1.90A/B/C2-115[»]
4PLUX-ray1.63A/B/C2-115[»]
4TRFX-ray1.63A/B/C2-115[»]
4TRUX-ray1.81A/B/C2-115[»]
4WR8X-ray2.60A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R2-115[»]
4WRBX-ray1.81A/B/C2-115[»]
4XX7X-ray1.77A/B/C2-115[»]
4XX8X-ray1.77A/B/C3-115[»]
4Z15X-ray1.60A/B/C3-115[»]
4Z1TX-ray1.50A/B/C3-115[»]
4Z1UX-ray2.05A/B/C/D/E/F3-115[»]
5B4OX-ray1.37A/B/C2-115[»]
5BS9X-ray1.98A/B/C2-115[»]
5BSCX-ray1.89A/B/C2-115[»]
5BSIX-ray2.00A/B/C/D/E/F/G/J2-115[»]
5BSJX-ray2.00A/B/C2-115[»]
5EIZX-ray1.96A/B/C2-115[»]
5HVSX-ray1.75A/B/C2-115[»]
5HVTX-ray1.75A/B/C2-115[»]
5HVVX-ray1.90A/B/C3-115[»]
5J7PX-ray1.85A/B/C2-115[»]
5J7QX-ray2.05A/B/C2-115[»]
5UMJX-ray1.61A/B/C2-115[»]
5UMKX-ray1.73A/B/C2-115[»]
5UZYX-ray1.71A/B/C2-115[»]
5V70X-ray1.94A/B/C2-115[»]
5V73X-ray1.68A/B/C2-115[»]
5XEJX-ray2.50A/B/C2-115[»]
6B1CX-ray2.16A/B/C2-115[»]
6B1KX-ray1.17A/B/C2-115[»]
6B2CX-ray2.00A/B/C2-115[»]
6BG6X-ray1.52A/B/C2-115[»]
6BG7X-ray2.54A/B/C2-115[»]
6CB5X-ray1.78A/B/C2-115[»]
6CBFX-ray2.30A/B/C2-115[»]
6CBGX-ray2.00A/B/C2-115[»]
6CBHX-ray2.00A/B/C2-115[»]
6FVEX-ray1.41A/B/C2-115[»]
6FVHX-ray1.40A/B/C2-115[»]
ProteinModelPortaliP14174
SMRiP14174
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110428, 62 interactors
DIPiDIP-31137N
IntActiP14174, 23 interactors
MINTiP14174
STRINGi9606.ENSP00000215754

Chemistry databases

BindingDBiP14174
ChEMBLiCHEMBL2085
DrugBankiDB07718 3-(4-HYDROXY-PHENYL)PYRUVIC ACID
DB08334 3-FLUORO-4-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIME
DB08333 4-HYDROXYBENZALDEHYDE O-(CYCLOHEXYLCARBONYL)OXIME
DB02728 7-Hydroxy-2-Oxo-Chromene-3-Carboxylic Acid Ethyl Ester
DB04272 Citric Acid

PTM databases

iPTMnetiP14174
PhosphoSitePlusiP14174
SwissPalmiP14174

Polymorphism and mutation databases

DMDMi1170955

2D gel databases

SWISS-2DPAGEiP14174

Proteomic databases

EPDiP14174
MaxQBiP14174
PaxDbiP14174
PeptideAtlasiP14174
PRIDEiP14174
ProteomicsDBi53030
TopDownProteomicsiP14174

Protocols and materials databases

DNASUi4282
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215754; ENSP00000215754; ENSG00000240972
ENST00000613839; ENSP00000482779; ENSG00000276701
GeneIDi4282
KEGGihsa:4282
UCSCiuc002zyr.2 human

Organism-specific databases

CTDi4282
DisGeNETi4282
EuPathDBiHostDB:ENSG00000240972.1
GeneCardsiMIF
H-InvDBiHIX0041297
HGNCiHGNC:7097 MIF
HPAiCAB005284
HPA003868
MalaCardsiMIF
MIMi153620 gene
604302 phenotype
neXtProtiNX_P14174
OpenTargetsiENSG00000240972
Orphaneti85414 Systemic-onset juvenile idiopathic arthritis
PharmGKBiPA30819
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1759 Eukaryota
ENOG41122MF LUCA
GeneTreeiENSGT00910000144267
HOGENOMiHOG000112325
HOVERGENiHBG003240
InParanoidiP14174
KOiK07253
OMAiPDRIYIN
OrthoDBiEOG091G0ZNJ
PhylomeDBiP14174
TreeFamiTF313853

Enzyme and pathway databases

BRENDAi5.3.2.1 2681
5.3.3.12 2681
ReactomeiR-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-6798695 Neutrophil degranulation
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
SIGNORiP14174

Miscellaneous databases

EvolutionaryTraceiP14174
GeneWikiiMacrophage_migration_inhibitory_factor
GenomeRNAii4282
PROiPR:P14174
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000240972 Expressed in 89 organ(s), highest expression level in left adrenal gland
CleanExiHS_MIF
ExpressionAtlasiP14174 baseline and differential
GenevisibleiP14174 HS

Family and domain databases

Gene3Di3.30.429.10, 1 hit
InterProiView protein in InterPro
IPR001398 Macrophage_inhib_fac
IPR019829 Macrophage_inhib_fac_CS
IPR014347 Tautomerase/MIF_sf
PANTHERiPTHR11954 PTHR11954, 1 hit
PfamiView protein in Pfam
PF01187 MIF, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD004816 Macrophage_inhib_fac, 1 hit
SUPFAMiSSF55331 SSF55331, 1 hit
PROSITEiView protein in PROSITE
PS01158 MIF, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMIF_HUMAN
AccessioniPrimary (citable) accession number: P14174
Secondary accession number(s): A5Z1R8
, B2R4S3, Q2V4Y5, Q6FHV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 216 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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
  3. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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