P80177 (MIF_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Macrophage migration inhibitory factor
Short name=MIF
EC=5.3.2.1

Alternative name(s):
L-dopachrome isomerase
L-dopachrome tautomerase
EC=5.3.3.12
Phenylpyruvate tautomerase
p12A

Gene names

Name:

MIF

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	115 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.
Subunit structure	Homotrimer. Interacts with BNIPL By similarity. Interacts with the CD74 extracellular domain. Interacts with COPS5 and with the CXCR2 extracellular domain By similarity.
Subcellular location	Secreted By similarity. Cytoplasm. 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.
Sequence similarities	Belongs to the MIF family.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cytoplasm Secreted
Molecular function	Cytokine Isomerase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator Inferred from electronic annotation. Source: Compara cell aging Inferred from electronic annotation. Source: Compara cell proliferation Inferred from electronic annotation. Source: Compara cell surface receptor signaling pathway Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara negative regulation of cell aging Inferred from electronic annotation. Source: Compara negative regulation of cell cycle arrest Inferred from electronic annotation. Source: Compara negative regulation of cellular protein metabolic process Inferred from electronic annotation. Source: Compara negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of mature B cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of myeloid cell apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of arachidonic acid secretion Inferred from electronic annotation. Source: Compara positive regulation of chemokine (C-X-C motif) ligand 2 production Inferred from electronic annotation. Source: Compara positive regulation of cytokine secretion Inferred from electronic annotation. Source: Compara positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of lipopolysaccharide-mediated signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of myeloid leukocyte cytokine production involved in immune response Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of prostaglandin secretion involved in immune response Inferred from electronic annotation. Source: Compara positive regulation of protein kinase A signaling cascade Inferred from electronic annotation. Source: Compara prostaglandin biosynthetic process Inferred from electronic annotation. Source: Compara protein homotrimerization Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cell surface binding Inferred from electronic annotation. Source: Compara chemoattractant activity Inferred from electronic annotation. Source: Compara dopachrome isomerase activity Inferred from sequence or structural similarity. Source: UniProtKB phenylpyruvate tautomerase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.2 Ref.4
	Chain	2 – 115	114	Macrophage migration inhibitory factor		PRO_0000158061
Sites
	Active site	2	1	Proton acceptor; via imino nitrogen By similarity
	Binding site	33	1	Substrate By similarity
	Binding site	65	1	Substrate; via amide nitrogen By similarity
	Binding site	98	1	Substrate By similarity
Amino acid modifications
	Modified residue	78	1	N6-acetyllysine By similarity
Experimental info
	Sequence conflict	99 – 100	2	FC → YY in AAD38354. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P80177 [UniParc]. Last modified January 23, 2007. Version 6. Checksum: 750242BFF691975E	FASTA	115	12,343
	10 20 30 40 50 60 MPMFVVNTNV PRASVPDGLL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF GGSSEPCALC 70 80 90 100 110 SLHSIGKIGG AQNRSYSKLL CGLLTERLRI SPDRIYINFC DMNAANVGWN GSTFA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	NIH - Mammalian Gene Collection (MGC) project Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Crossbred X Angus. Tissue: Ileum.
[2]	"A diversified family of 12-kDa proteins with a high amino acid sequence similarity to macrophage migration-inhibitory factor (MIF)." Galat A., Riviere S., Bouet F., Menez A. Eur. J. Biochem. 224:417-421(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-115. Tissue: Brain.
[3]	"Macrophage migration inhibitory factor in the bovine corpus luteum: characterization of steady-state messenger ribonucleic acid and immunohistochemical localization." Bove S.E., Petroff M.G., Nishibori M., Pate J.L. Biol. Reprod. 62:879-885(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-104. Tissue: Corpus luteum.
[4]	"Purification of macrophage migration inhibitory factor (MIF) from bovine brain cytosol." Galat A., Riviere S., Bouet F. FEBS Lett. 319:233-236(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-40. Tissue: Brain.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC102066 mRNA. Translation: AAI02067.1. AF119571 mRNA. Translation: AAD38354.1.
IPI	IPI00694142.
PIR	S32394. S48158.
RefSeq	NP_001028780.1. NM_001033608.1.
UniGene	Bt.15528.
3D structure databases
ProteinModelPortal	P80177.
SMR	P80177. Positions 1-115.
ModBase	Search...
Proteomic databases
PRIDE	P80177.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000009699; ENSBTAP00000009699; ENSBTAG00000007375.
GeneID	280858.
KEGG	bta:280858.
Organism-specific databases
CTD	4282.
Phylogenomic databases
eggNOG	NOG08790.
GeneTree	ENSGT00530000063544.
HOGENOM	HOG000112325.
HOVERGEN	HBG003240.
InParanoid	P80177.
KO	K07253.
OMA	PDRIYIN.
OrthoDB	EOG49GKJ5.
Enzyme and pathway databases
SABIO-RK	P80177.
Family and domain databases
InterPro	IPR001398. Macrophage_inhib_fac. IPR019829. Macrophage_inhib_fac_CS. IPR014347. Tautomerase/MIF_sf. [Graphical view]
PANTHER	PTHR11954. PTHR11954. 1 hit.
Pfam	PF01187. MIF. 1 hit. [Graphical view]
ProDom	PD004816. Macrophage_inhib_fac. 1 hit. [Graphical view] [Entries sharing at least one domain]
SUPFAM	SSF55331. SSF55331. 1 hit.
PROSITE	PS01158. MIF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20805002.

Entry information

Entry name

MIF_BOVIN

Accession

Primary (citable) accession number: P80177
Secondary accession number(s): Q3T190, Q9XT46

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 104 of the entry and version 6 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program