IED Industry Enzyme Database

Detail Information for IndEnz0002008089
IED ID IndEnz0002008089
Enzyme Type ID protease008089
Protein Name Macrophage migration inhibitory factor
MIF
EC 5.3.2.1
Glycosylation-inhibiting factor
GIF
L-dopachrome isomerase
L-dopachrome tautomerase
EC 5.3.3.12
Phenylpyruvate tautomerase
Gene Name MIF GLIF MMIF
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MPMFIVNTNVPRASVPDGFLSELTQQLAQATGKPPQYIAVHVVPDQLMAFGGSSEPCALCSLHSIGKIGGAQNRSYSKLLCGLLAERLRISPDRVYINYYDMNAANVGWNNSTFA
Enzyme Length 115
Uniprot Accession Number P14174
Absorption
Active Site ACT_SITE 2; /note=Proton acceptor; via imino nitrogen
Activity Regulation
Binding Site BINDING 33; /note=Substrate; BINDING 65; /note=Substrate; via amide nitrogen; BINDING 98; /note=Substrate
Calcium Binding
catalytic Activity 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; Evidence={ECO:0000269|PubMed:17526494};
DNA Binding
EC Number 5.3.2.1; 5.3.3.12
Enzyme Function 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 (PubMed:17526494). 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:17526494, ECO:0000269|PubMed:23776208}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (1); Beta strand (7); Binding site (3); Chain (1); Helix (6); Initiator methionine (1); Modified residue (2); Mutagenesis (1); Sequence conflict (6)
Keywords 3D-structure;Acetylation;Cytokine;Cytoplasm;Direct protein sequencing;Immunity;Inflammatory response;Innate immunity;Isomerase;Reference proteome;Secreted
Interact With O43521-2; P00533; Q92743; Itself; Q96HA8
Induction 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}.
Subcellular Location 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}.
Modified Residue MOD_RES 78; /note=N6-acetyllysine; alternate; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 78; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:P34884
Post Translational Modification
Signal Peptide
Structure 3D X-ray crystallography (94)
Cross Reference PDB 1CA7; 1CGQ; 1GCZ; 1GD0; 1GIF; 1LJT; 1MIF; 1P1G; 2OOH; 2OOW; 2OOZ; 3B9S; 3CE4; 3DJH; 3DJI; 3HOF; 3IJG; 3IJJ; 3JSF; 3JSG; 3JTU; 3L5P; 3L5R; 3L5S; 3L5T; 3L5U; 3L5V; 3SMB; 3SMC; 3U18; 3WNR; 3WNS; 3WNT; 4ETG; 4EUI; 4EVG; 4F2K; 4GRN; 4GRO; 4GRP; 4GRQ; 4GRR; 4GRU; 4GUM; 4K9G; 4OSF; 4OYQ; 4P01; 4P0H; 4PKK; 4PKZ; 4PLU; 4TRF; 4TRU; 4WR8; 4WRB; 4XX7; 4XX8; 4Z15; 4Z1T; 4Z1U; 5B4O; 5BS9; 5BSC; 5BSI; 5BSJ; 5EIZ; 5HVS; 5HVT; 5HVV; 5J7P; 5J7Q; 5UMJ; 5UMK; 5UZY; 5V70; 5V73; 5XEJ; 6B1C; 6B1K; 6B2C; 6BG6; 6BG7; 6CB5; 6CBF; 6CBG; 6CBH; 6FVE; 6FVH; 6OY8; 6OYB; 6OYE; 6OYG; 6PEG;
Mapped Pubmed ID 11920501; 11978887; 11985788; 11997397; 12009356; 12070782; 12109441; 12126556; 12180727; 12186913; 12218292; 12218308; 12235522; 12355488; 12402212; 12445161; 12480958; 12507885; 12576459; 12607777; 12612911; 12615835; 12626594; 12631237; 12667094; 12738641; 12740374; 12746913; 12796500; 12847682; 12965208; 14502271; 14551601; 14581488; 14607690; 14736878; 14760795; 14962818; 15018649; 15065001; 15146413; 15146431; 15170913; 15216464; 15231747; 15286457; 15292349; 15304087; 15308783; 15545061; 15545824; 15576462; 15585204; 15585220; 15612021; 15630728; 15659324; 15757663; 15800984; 15815686; 15820792; 15838879; 15910495; 15910597; 16000172; 16038020; 16051683; 16085663; 16115023; 16133063; 16169070; 16179637; 16189514; 16200611; 16205314; 16220288; 16224818; 16247506; 16285950; 16314470; 16314559; 16317091; 16369812; 16385258; 16388506; 16488392; 16527487; 16538639; 16677407; 16709839; 16724072; 16767681; 16780713; 16807115; 16820919; 16839849; 16854377; 16861224; 16872482; 16893895; 16929348; 17005573; 17029206; 17075815; 17108334; 17142775; 17166737; 17172590; 17181929; 17206642; 17215861; 17224449; 17353931; 17435771; 17438452; 17438455; 17495357; 17541237; 17559578; 17591062; 17592555; 17620429; 17658526; 17706208; 17709373; 17712545; 17728788; 17763209; 17786285; 17854804; 17854909; 17869648; 17906677; 17912466; 18034423; 18037272; 18054247; 18060744; 18074864; 18078632; 18081874; 18097599; 18165264; 18171527; 18171602; 18177450; 18228042; 18239193; 18242614; 18261992; 18270460; 18356846; 18362243; 18426738; 18466513; 18469521; 18474653; 18490733; 18493321; 18502749; 18618071; 18676531; 18677096; 18680514; 18684922; 18710704; 18720262; 18794110; 18795803; 18815136; 18832726; 18852457; 18853133; 18930766; 19009023; 19038405; 19062717; 19081768; 19109179; 19155217; 19157791; 19167373; 19170716; 19188484; 19196797; 19260777; 19299454; 19317738; 19346297; 19376177; 19394321; 19417556; 19423540; 19428548; 19463016; 19464392; 19475570; 19591577; 19601712; 19602265; 19644855; 19665027; 19720544; 19723024; 19724898; 19726058; 19737008; 19747950; 19759012; 19762145; 19773451; 19776019; 19776337; 19829123; 19836948; 19913121; 19938192; 19941661; 19950249; 20038293; 20085845; 20127054; 20149326; 20178462; 20185308; 20193596; 20200619; 20203087; 20233515; 20237496; 20303284; 20346241; 20360068; 20369477; 20380014; 20382217; 20383199; 20406964; 20438785; 20439102; 20447688; 20448056; 20452482; 20460119; 20467327; 20471506; 20499270; 20534506; 20546256; 20562859; 20573157; 20598902; 20621719; 20628086; 20646540; 20673868; 20805296; 20807568; 20811626; 20829434; 20847814; 20861157; 20863520; 20872800; 20878093; 20980171; 21030269; 21045753; 21071513; 21087445; 21106938; 21162929; 21168764; 21169549; 21208809; 21209875; 21269946; 21281800; 21283538; 21283592; 21360573; 21401926; 21417823; 21512965; 21515791; 21553324; 21575460; 21607559; 21623990; 21641401; 21684012; 21725855; 21750916; 21773885; 21792010; 21817065; 21823060; 21848392; 21852299; 21875883; 21890178; 21988832; 21990375; 22007254; 22079264; 22099602; 22127710; 22166284; 22174124; 22206839; 22271573; 22302395; 22327470; 22415145; 22449335; 22451332; 22461895; 22543583; 22609310; 22611320; 22623428; 22649515; 22676646; 22693633; 22742858; 22759564; 22782901; 22810585; 22813781; 22820623; 22821831; 22883521; 22892326; 22893706; 22898393; 22909194; 22927777; 22931430; 22939113; 22949182; 22952837; 23023114; 23028743; 23043599; 23050964; 23060578; 23064787; 23068083; 23125447; 23179933; 23207293; 23246423; 23272137; 23315862; 23354841; 23383040; 23402792; 23403077; 23410506; 23411097; 23451183; 23497377; 23523092; 23526214; 23537651; 23552723; 23566229; 23650620; 23707797; 23721694; 23759989; 23770720; 23794947; 23846621; 23882081; 23895962; 23913513; 23978362; 23985752; 24003215; 24039418; 24066864; 24091309; 24098445; 24138931; 24151396; 24158957; 24167613; 24194192; 24274936; 24356968; 24366206; 24379579; 24384723; 24396292; 24424397; 24429801; 24441872; 24490973; 24527464; 24530749; 24569872; 24644543; 24667663; 24683185; 24687413; 24826917; 24840392; 24850900; 24862346; 24879618; 24932684; 24939415; 25022961; 25050663; 25056219; 25105152; 25108206; 25168062; 25172501; 25329590; 25458401; 25460285; 25463068; 25487600; 25503271; 25530499; 25561410; 25593081; 25600533; 25697265; 25712213; 25712805; 25716200; 25730019; 25743213; 25762421; 25821795; 25861163; 25930990; 25966103; 25972622; 25998484; 26005773; 26020638; 26039541; 26087187; 26107210; 26138061; 26139098; 26161389; 26209628; 26234719; 26272322; 26280537; 26281331; 26345783; 26348853; 26352431; 26364929; 26403072; 26412712; 26426302; 26453918; 26485680; 26496610; 26530123; 26535701; 26541175; 26542751; 26549761; 26603621; 26638028; 26638075; 26656832; 26719579; 26741693; 26750167; 26752645; 26783235; 26825917; 26829742; 26851955; 26852939; 26858459; 26866879; 26872252; 26883190; 26911630; 26933127; 26935642; 26952810; 26976591; 26980763; 26985869; 27049098; 27079941; 27101443; 27105877; 27145382; 27156768; 27157615; 27163877; 27190066; 27197190; 27207917; 27226569; 27270225; 27298517; 27299179; 27337548; 27364992; 27381622; 27402018; 27426952; 27434219; 27453287; 27460703; 27509135; 27544048; 27573366; 27598332; 27612504; 27619729; 27696094; 27721403; 27793992; 27811451; 27846469; 27872288; 28086136; 28160516; 28230058; 28331211; 28338494; 28366792; 28370484; 28407372; 28429502; 28513076; 28574571; 28578664; 28624489; 28642171; 28656911; 28657145; 28668810; 28703031; 28704499; 28729134; 28768722; 28801314; 28823650; 28905103; 28912189; 28923927; 28965181; 28993199; 29079416; 29096759; 29120365; 29186613; 29207023; 29208960; 29239244; 29247897; 29257298; 29259749; 29289260; 29371591; 29397904; 29412660; 29487418; 29487601; 29575754; 29581527; 29601965; 29661540; 29669180; 29669352; 29690804; 29702687; 29723777; 29759141; 29769287; 29773680; 29807404; 29856236; 29863307; 29870971; 29896883; 29953750; 29996006; 30009530; 30041958; 30074218; 30077612; 30108299; 30120767; 30160778; 30195326; 30226561; 30226567; 30274020; 30295645; 30348174; 30371153; 30383785; 30467094; 30503813; 30506423; 30511959; 30567353; 30569239; 30616035; 30626475; 30628898; 30667094; 30747392; 30802541; 30841876; 30868074; 30903991; 30968541; 30983881; 31036057; 31036774; 31069878; 31108057; 31154458; 31173234; 31174614; 31180524; 31219646; 31267487; 31370326; 31422388; 31499270; 31701681; 31752120; 31790982; 31811089; 31866994; 31924846; 31936865; 31960418; 31973534; 31978276; 32044623; 32196575; 32279906; 32317702; 32375447; 32410863; 32433911; 32515296; 32525926; 32560699; 32582913; 32683105; 32705792; 32769903; 32800392; 32811420; 32885302; 33046033; 33046825; 33062162; 33148606; 33179462; 33181151; 33279833; 33330982; 33385298; 33401503; 33525493; 33542244; 33610191; 33645533; 33673075; 33823474; 33839715; 33850223; 34012010; 34013373; 34129019; 34278453; 34306312; 34314630; 34384784; 34443554; 34662363;
Motif
Gene Encoded By
Mass 12,476
Kinetics 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};
Metal Binding
Rhea ID RHEA:17097; RHEA:13041
Cross Reference Brenda 5.3.2.1;5.3.3.12;