P14174 · MIF_HUMAN
- ProteinMacrophage migration inhibitory factor
- GeneMIF
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids115 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens (PubMed:15908412, PubMed:17443469, PubMed:23776208).
The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense (PubMed:15908412, PubMed:17443469, PubMed:23776208).
Counteracts the anti-inflammatory activity of glucocorticoids (PubMed:15908412, PubMed:17443469, PubMed:23776208).
Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known (PubMed:11439086, PubMed:17526494).
It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (PubMed:11439086, PubMed:17526494).
The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense (PubMed:15908412, PubMed:17443469, PubMed:23776208).
Counteracts the anti-inflammatory activity of glucocorticoids (PubMed:15908412, PubMed:17443469, PubMed:23776208).
Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known (PubMed:11439086, PubMed:17526494).
It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (PubMed:11439086, PubMed:17526494).
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 activity
- 3-phenylpyruvate = enol-phenylpyruvate
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
249 μM | phenylpyruvate | |||||
168 μM | p-hydroxyphenylpyruvate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
2113 μmol/min/mg | toward phenylpyruvate | ||||
524 μmol/min/mg | toward p-hydroxyphenylpyruvate |
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 2 | Proton acceptor; via imino nitrogen | ||||
Sequence: P | ||||||
Binding site | 33 | substrate | ||||
Sequence: K | ||||||
Binding site | 65 | substrate | ||||
Sequence: I | ||||||
Binding site | 98 | substrate | ||||
Sequence: N |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMacrophage migration inhibitory factor
- EC number
- Short namesMIF
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP14174
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Rheumatoid arthritis systemic juvenile (RASJ)
- Note
- 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 alsoMIM:604302
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 111 | Causes formation of interchain disulfide bonds with Cys-81 from another subunit. | ||||
Sequence: N → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 362 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Chain | PRO_0000158062 | 2-115 | UniProt | Macrophage migration inhibitory factor | |||
Sequence: PMFIVNTNVPRASVPDGFLSELTQQLAQATGKPPQYIAVHVVPDQLMAFGGSSEPCALCSLHSIGKIGGAQNRSYSKLLCGLLAERLRISPDRVYINYYDMNAANVGWNNSTFA | |||||||
Modified residue (large scale data) | 14 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 78 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 78 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Up-regulated in concanavalin-A-treated lymphocytes. Up-regulated in macrophages upon exposure to M.tuberculosis antigens.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homotrimer (PubMed:23776208, PubMed:8610159).
Interacts with CXCR2 extracellular domain (By similarity).
Interacts with the CD74 extracellular domain, USO1, COPS5 and BNIPL (PubMed:11089976, PubMed:12681488, PubMed:12782713, PubMed:19454686, PubMed:23776208).
Interacts with CXCR2 extracellular domain (By similarity).
Interacts with the CD74 extracellular domain, USO1, COPS5 and BNIPL (PubMed:11089976, PubMed:12681488, PubMed:12782713, PubMed:19454686, PubMed:23776208).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P14174 | BCL2L11 O43521-2 | 5 | EBI-372712, EBI-526420 | |
BINARY | P14174 | EGFR P00533 | 3 | EBI-372712, EBI-297353 | |
BINARY | P14174 | HTRA1 Q92743 | 3 | EBI-372712, EBI-352256 | |
BINARY | P14174 | MIF P14174 | 7 | EBI-372712, EBI-372712 | |
BINARY | P14174 | NTAQ1 Q96HA8 | 4 | EBI-372712, EBI-741158 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length115
- Mass (Da)12,476
- Last updated2007-01-23 v4
- Checksum56D51107C05286B2
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 57-59 | in Ref. 6; ABQ95571 | ||||
Sequence: CAL → WAF | ||||||
Sequence conflict | 67 | in Ref. 9; CAG46452 | ||||
Sequence: K → R | ||||||
Sequence conflict | 79 | in Ref. 9; CAG46452 | ||||
Sequence: L → Q | ||||||
Sequence conflict | 81 | in Ref. 6; ABQ95571 | ||||
Sequence: C → F | ||||||
Sequence conflict | 106 | in Ref. 1; AAA36315 | ||||
Sequence: N → S | ||||||
Sequence conflict | 113 | in Ref. 6; ABQ95571 | ||||
Sequence: T → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M25639 EMBL· GenBank· DDBJ | AAA36315.1 EMBL· GenBank· DDBJ | mRNA | ||
L10612 EMBL· GenBank· DDBJ | AAA35892.1 EMBL· GenBank· DDBJ | mRNA | ||
Z23063 EMBL· GenBank· DDBJ | CAA80598.1 EMBL· GenBank· DDBJ | mRNA | ||
L19686 EMBL· GenBank· DDBJ | AAA21814.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF469046 EMBL· GenBank· DDBJ | AAL78635.1 EMBL· GenBank· DDBJ | mRNA | ||
EF611126 EMBL· GenBank· DDBJ | ABQ95571.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456520 EMBL· GenBank· DDBJ | CAG30406.1 EMBL· GenBank· DDBJ | mRNA | ||
AK311929 EMBL· GenBank· DDBJ | BAG34870.1 EMBL· GenBank· DDBJ | mRNA | ||
CR407644 EMBL· GenBank· DDBJ | CAG28572.1 EMBL· GenBank· DDBJ | mRNA | ||
CR541651 EMBL· GenBank· DDBJ | CAG46452.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007148 EMBL· GenBank· DDBJ | AAP35812.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ307455 EMBL· GenBank· DDBJ | ABB96245.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471095 EMBL· GenBank· DDBJ | EAW59620.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC000447 EMBL· GenBank· DDBJ | AAH00447.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007676 EMBL· GenBank· DDBJ | AAH07676.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008914 EMBL· GenBank· DDBJ | AAH08914.1 EMBL· GenBank· DDBJ | mRNA | ||
BC013976 EMBL· GenBank· DDBJ | AAH13976.1 EMBL· GenBank· DDBJ | mRNA | ||
BC022414 EMBL· GenBank· DDBJ | AAH22414.1 EMBL· GenBank· DDBJ | mRNA | ||
BC053376 EMBL· GenBank· DDBJ | AAH53376.1 EMBL· GenBank· DDBJ | mRNA | ||
M95775 EMBL· GenBank· DDBJ | AAA36179.1 EMBL· GenBank· DDBJ | mRNA |