UniProt functional annotation for P14174



	UniProt functional annotation for P14174

UniProt code: P14174.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:15908412, ECO:0000269|PubMed:17443469, ECO:0000269|PubMed:23776208}.

Catalytic activity: Reaction=3-phenylpyruvate = enol-phenylpyruvate; Xref=Rhea:RHEA:17097, ChEBI:CHEBI:16815, ChEBI:CHEBI:18005; EC=5.3.2.1;

Catalytic activity: Reaction=L-dopachrome = 5,6-dihydroxyindole-2-carboxylate; Xref=Rhea:RHEA:13041, ChEBI:CHEBI:16875, ChEBI:CHEBI:57509; EC=5.3.3.12;

Biophysicochemical properties: Kinetic parameters: KM=249 uM for phenylpyruvate {ECO:0000269|PubMed:11439086}; KM=168 uM for p-hydroxyphenylpyruvate {ECO:0000269|PubMed:11439086}; Vmax=2113 umol/min/mg enzyme toward phenylpyruvate {ECO:0000269|PubMed:11439086}; Vmax=524 umol/min/mg enzyme toward p-hydroxyphenylpyruvate {ECO:0000269|PubMed:11439086};

Subunit: Homotrimer. Interacts with CXCR2 extracellular domain (By similarity). Interacts with the CD74 extracellular domain, COPS5 and BNIPL. {ECO:0000250, ECO:0000269|PubMed:11089976, ECO:0000269|PubMed:11170644, ECO:0000269|PubMed:12681488, ECO:0000269|PubMed:12782713, ECO:0000269|PubMed:17526494, ECO:0000269|PubMed:19090677, ECO:0000269|PubMed:19454686, ECO:0000269|PubMed:23776208}.

Subcellular location: Secreted {ECO:0000269|PubMed:15908412, ECO:0000269|PubMed:19454686, ECO:0000269|PubMed:2552447, ECO:0000269|PubMed:8234256}. Cytoplasm {ECO:0000269|PubMed:11089976, ECO:0000269|PubMed:19454686}. 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. {ECO:0000269|PubMed:15908412}.

Induction: Up-regulated in concanavalin-A-treated lymphocytes. Up- regulated in macrophages upon exposure to M.tuberculosis antigens. {ECO:0000269|PubMed:15908412, ECO:0000269|PubMed:2552447}.

Disease: Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An 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. {ECO:0000269|PubMed:11508429}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

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.

Similarity: Belongs to the MIF family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:15908412, ECO:0000269\|PubMed:17443469, ECO:0000269\|PubMed:23776208}.


Catalytic activity:		Reaction=3-phenylpyruvate = enol-phenylpyruvate; Xref=Rhea:RHEA:17097, ChEBI:CHEBI:16815, ChEBI:CHEBI:18005; EC=5.3.2.1;
Catalytic activity:		Reaction=L-dopachrome = 5,6-dihydroxyindole-2-carboxylate; Xref=Rhea:RHEA:13041, ChEBI:CHEBI:16875, ChEBI:CHEBI:57509; EC=5.3.3.12;
Biophysicochemical properties:		Kinetic parameters: KM=249 uM for phenylpyruvate {ECO:0000269\|PubMed:11439086}; KM=168 uM for p-hydroxyphenylpyruvate {ECO:0000269\|PubMed:11439086}; Vmax=2113 umol/min/mg enzyme toward phenylpyruvate {ECO:0000269\|PubMed:11439086}; Vmax=524 umol/min/mg enzyme toward p-hydroxyphenylpyruvate {ECO:0000269\|PubMed:11439086};
Subunit:		Homotrimer. Interacts with CXCR2 extracellular domain (By similarity). Interacts with the CD74 extracellular domain, COPS5 and BNIPL. {ECO:0000250, ECO:0000269\|PubMed:11089976, ECO:0000269\|PubMed:11170644, ECO:0000269\|PubMed:12681488, ECO:0000269\|PubMed:12782713, ECO:0000269\|PubMed:17526494, ECO:0000269\|PubMed:19090677, ECO:0000269\|PubMed:19454686, ECO:0000269\|PubMed:23776208}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:15908412, ECO:0000269\|PubMed:19454686, ECO:0000269\|PubMed:2552447, ECO:0000269\|PubMed:8234256}. Cytoplasm {ECO:0000269\|PubMed:11089976, ECO:0000269\|PubMed:19454686}. 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. {ECO:0000269\|PubMed:15908412}.
Induction:		Up-regulated in concanavalin-A-treated lymphocytes. Up- regulated in macrophages upon exposure to M.tuberculosis antigens. {ECO:0000269\|PubMed:15908412, ECO:0000269\|PubMed:2552447}.
Disease:		Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An 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. {ECO:0000269\|PubMed:11508429}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
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.
Similarity:		Belongs to the MIF family. {ECO:0000305}.