MIF_MACFA
ID MIF_MACFA Reviewed; 115 AA.
AC Q4R549;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Macrophage migration inhibitory factor;
DE Short=MIF;
DE EC=5.3.2.1 {ECO:0000250|UniProtKB:P14174};
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; ORFNames=QccE-19130;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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 -!- SIMILARITY: Belongs to the MIF family. {ECO:0000305}.
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DR EMBL; AB169695; BAE01776.1; -; mRNA.
DR RefSeq; NP_001270626.1; NM_001283697.1.
DR AlphaFoldDB; Q4R549; -.
DR SMR; Q4R549; -.
DR STRING; 9541.XP_005595437.1; -.
DR PRIDE; Q4R549; -.
DR Ensembl; ENSMFAT00000007268; ENSMFAP00000033043; ENSMFAG00000003050.
DR GeneID; 101867092; -.
DR CTD; 4282; -.
DR VEuPathDB; HostDB:ENSMFAG00000003050; -.
DR eggNOG; KOG1759; Eukaryota.
DR GeneTree; ENSGT00940000155608; -.
DR OMA; YINFFDM; -.
DR OrthoDB; 1451925at2759; -.
DR Proteomes; UP000233100; Chromosome 10.
DR Bgee; ENSMFAG00000003050; Expressed in pituitary gland and 13 other tissues.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0042056; F:chemoattractant activity; IEA:Ensembl.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005126; F:cytokine receptor binding; IEA:Ensembl.
DR GO; GO:0004167; F:dopachrome isomerase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0050178; F:phenylpyruvate tautomerase activity; IEA:UniProtKB-EC.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IEA:Ensembl.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; IEA:Ensembl.
DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0090238; P:positive regulation of arachidonic acid secretion; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0061081; P:positive regulation of myeloid leukocyte cytokine production involved in immune response; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0061078; P:positive regulation of prostaglandin secretion involved in immune response; IEA:Ensembl.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IEA:Ensembl.
DR GO; GO:0070207; P:protein homotrimerization; IEA:Ensembl.
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 3: Inferred from homology;
KW Acetylation; Cytokine; Cytoplasm; Immunity; Inflammatory response;
KW Innate immunity; Isomerase; Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P14174"
FT CHAIN 2..115
FT /note="Macrophage migration inhibitory factor"
FT /id="PRO_0000158063"
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"
SQ SEQUENCE 115 AA; 12476 MW; 56D51107C05286B2 CRC64;
MPMFIVNTNV PRASVPDGFL SELTQQLAQA TGKPPQYIAV HVVPDQLMAF GGSSEPCALC
SLHSIGKIGG AQNRSYSKLL CGLLAERLRI SPDRVYINYY DMNAANVGWN NSTFA
