MIF_RAT
ID MIF_RAT Reviewed; 115 AA.
AC P30904;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Macrophage migration inhibitory factor;
DE Short=MIF;
DE EC=5.3.2.1 {ECO:0000250|UniProtKB:P14174};
DE AltName: Full=Glutathione-binding 13 kDa protein;
DE AltName: Full=L-dopachrome isomerase;
DE AltName: Full=L-dopachrome tautomerase;
DE EC=5.3.3.12 {ECO:0000250|UniProtKB:P14174};
DE AltName: Full=Phenylpyruvate tautomerase;
GN Name=Mif;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7951062;
RA Sakai M., Nishihira J., Hibiya Y., Koyama Y., Nishi S.;
RT "Glutathione binding rat liver 13k protein is the homologue of the
RT macrophage migration inhibitory factor.";
RL Biochem. Mol. Biol. Int. 33:439-446(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lens;
RA Wen Y., Li G., Bekhor I.;
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=PVG/C;
RA Sleeman M.A., Huckle J.W., Robinson M., Jahoda C.A.B., Reynolds A.J.,
RA Whitehouse C.J.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-26.
RX PubMed=1436109; DOI=10.1038/360269a0;
RA Blocki F.A., Schlievert P.M., Wackett L.P.;
RT "Rat liver protein linking chemical and immunological detoxification
RT systems.";
RL Nature 360:269-270(1992).
RN [6]
RP PROTEIN SEQUENCE OF 2-12 AND 79-87, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Hippocampus;
RA Lubec G., Diao W., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RC TISSUE=Liver;
RX PubMed=8605628; DOI=10.1038/nsb0396-259;
RA Suzuki M., Sugimoto H., Nakagawa A., Tanaka I., Nishihira J., Sakai M.;
RT "Crystal structure of the macrophage migration inhibitory factor from rat
RT liver.";
RL Nat. Struct. Biol. 3:259-266(1996).
CC -!- FUNCTION: Pro-inflammatory cytokine involved in the innate immune
CC response to bacterial pathogens. The expression of MIF at sites of
CC inflammation suggests a role as mediator in regulating the function of
CC macrophages in host defense. Counteracts the anti-inflammatory activity
CC of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome
CC tautomerase activity (in vitro), but the physiological substrate is not
CC known. It is not clear whether the tautomerase activity has any
CC physiological relevance, and whether it is important for cytokine
CC activity. {ECO:0000250|UniProtKB:P14174}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-phenylpyruvate = enol-phenylpyruvate; Xref=Rhea:RHEA:17097,
CC ChEBI:CHEBI:16815, ChEBI:CHEBI:18005; EC=5.3.2.1;
CC Evidence={ECO:0000250|UniProtKB:P14174};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-dopachrome = 5,6-dihydroxyindole-2-carboxylate;
CC Xref=Rhea:RHEA:13041, ChEBI:CHEBI:16875, ChEBI:CHEBI:57509;
CC EC=5.3.3.12; Evidence={ECO:0000250|UniProtKB:P14174};
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with CXCR2 extracellular
CC domain (By similarity). Interacts with the CD74 extracellular domain,
CC USO1, COPS5 and BNIPL (By similarity). {ECO:0000250|UniProtKB:P14174,
CC ECO:0000250|UniProtKB:P34884}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P14174}.
CC Cytoplasm {ECO:0000250|UniProtKB:P14174}. Note=Does not have a
CC cleavable signal sequence and is secreted via a specialized, non-
CC classical pathway. Secreted by macrophages upon stimulation by
CC bacterial lipopolysaccharide (LPS), or by M.tuberculosis antigens.
CC {ECO:0000250|UniProtKB:P14174}.
CC -!- TISSUE SPECIFICITY: Expressed in a wide variety of organs including
CC brain, spleen, liver, muscle and kidney. {ECO:0000269|PubMed:7951062}.
CC -!- SIMILARITY: Belongs to the MIF family. {ECO:0000305}.
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DR EMBL; S73424; AAB32392.1; -; mRNA.
DR EMBL; U20999; AAA62644.1; -; mRNA.
DR EMBL; U62326; AAB04024.1; -; mRNA.
DR EMBL; BC061545; AAH61545.1; -; mRNA.
DR PIR; S27117; S27117.
DR RefSeq; NP_112313.1; NM_031051.1.
DR RefSeq; XP_008772068.1; XM_008773846.2.
DR RefSeq; XP_017457271.1; XM_017601782.1.
DR PDB; 1FIM; X-ray; 2.20 A; A=2-115.
DR PDBsum; 1FIM; -.
DR AlphaFoldDB; P30904; -.
DR SMR; P30904; -.
DR BioGRID; 249580; 2.
DR IntAct; P30904; 4.
DR MINT; P30904; -.
DR STRING; 10116.ENSRNOP00000008608; -.
DR ChEMBL; CHEMBL4524037; -.
DR iPTMnet; P30904; -.
DR PhosphoSitePlus; P30904; -.
DR SwissPalm; P30904; -.
DR jPOST; P30904; -.
DR PaxDb; P30904; -.
DR PRIDE; P30904; -.
DR Ensembl; ENSRNOT00000008608; ENSRNOP00000008608; ENSRNOG00000006589.
DR GeneID; 81683; -.
DR KEGG; rno:81683; -.
DR UCSC; RGD:621163; rat.
DR CTD; 4282; -.
DR RGD; 621163; Mif.
DR eggNOG; KOG1759; Eukaryota.
DR GeneTree; ENSGT00940000155608; -.
DR HOGENOM; CLU_129906_1_1_1; -.
DR InParanoid; P30904; -.
DR OMA; YINFFDM; -.
DR OrthoDB; 1451925at2759; -.
DR PhylomeDB; P30904; -.
DR TreeFam; TF313853; -.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR EvolutionaryTrace; P30904; -.
DR PRO; PR:P30904; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000006589; Expressed in ovary and 19 other tissues.
DR ExpressionAtlas; P30904; baseline and differential.
DR Genevisible; P30904; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042056; F:chemoattractant activity; ISO:RGD.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0005126; F:cytokine receptor binding; ISO:RGD.
DR GO; GO:0004167; F:dopachrome isomerase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0050178; F:phenylpyruvate tautomerase activity; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0002035; P:brain renin-angiotensin system; IMP:RGD.
DR GO; GO:0019752; P:carboxylic acid metabolic process; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0090398; P:cellular senescence; ISO:RGD.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
DR GO; GO:0042756; P:drinking behavior; IMP:RGD.
DR GO; GO:0001942; P:hair follicle development; IEP:RGD.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; ISO:RGD.
DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; ISO:RGD.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; ISO:RGD.
DR GO; GO:0002675; P:positive regulation of acute inflammatory response; IMP:RGD.
DR GO; GO:0090238; P:positive regulation of arachidonic acid secretion; ISO:RGD.
DR GO; GO:0048680; P:positive regulation of axon regeneration; IMP:RGD.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:RGD.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:RGD.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IMP:RGD.
DR GO; GO:0050778; P:positive regulation of immune response; IMP:RGD.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0061081; P:positive regulation of myeloid leukocyte cytokine production involved in immune response; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IMP:RGD.
DR GO; GO:0061078; P:positive regulation of prostaglandin secretion involved in immune response; ISO:RGD.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISO:RGD.
DR GO; GO:0070207; P:protein homotrimerization; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0032572; P:response to menaquinone; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0043588; P:skin development; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IMP:RGD.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR Gene3D; 3.30.429.10; -; 1.
DR InterPro; IPR001398; Macrophage_inhib_fac.
DR InterPro; IPR019829; Macrophage_inhib_fac_CS.
DR InterPro; IPR014347; Tautomerase/MIF_sf.
DR PANTHER; PTHR11954; PTHR11954; 1.
DR Pfam; PF01187; MIF; 1.
DR SUPFAM; SSF55331; SSF55331; 1.
DR PROSITE; PS01158; MIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing;
KW Immunity; Inflammatory response; Innate immunity; Isomerase;
KW Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1436109, ECO:0000269|Ref.6"
FT CHAIN 2..115
FT /note="Macrophage migration inhibitory factor"
FT /id="PRO_0000158068"
FT ACT_SITE 2
FT /note="Proton acceptor; via imino nitrogen"
FT /evidence="ECO:0000250|UniProtKB:P34884"
FT BINDING 33
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14174"
FT BINDING 65
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14174"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14174"
FT MOD_RES 78
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P14174"
FT MOD_RES 78
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P34884"
FT CONFLICT 51
FT /note="S -> R (in Ref. 2; AAA62644)"
FT /evidence="ECO:0000305"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:1FIM"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:1FIM"
FT HELIX 19..31
FT /evidence="ECO:0007829|PDB:1FIM"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:1FIM"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:1FIM"
FT STRAND 58..66
FT /evidence="ECO:0007829|PDB:1FIM"
FT HELIX 70..88
FT /evidence="ECO:0007829|PDB:1FIM"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1FIM"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:1FIM"
SQ SEQUENCE 115 AA; 12477 MW; 8333F7B81B098445 CRC64;
MPMFIVNTNV PRASVPEGFL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF SGTSDPCALC
SLHSIGKIGG AQNRNYSKLL CGLLSDRLHI SPDRVYINYY DMNAANVGWN GSTFA
