P14174 (MIF_HUMAN) 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):
Glycosylation-inhibiting factor
Short name=GIF
L-dopachrome isomerase
L-dopachrome tautomerase
EC=5.3.3.12
Phenylpyruvate tautomerase

Gene names

Name:	MIF
Synonyms:	GLIF, MMIF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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. Ref.23 Ref.24
Catalytic activity	Keto-phenylpyruvate = enol-phenylpyruvate. Ref.32 Ref.34 L-dopachrome = 5,6-dihydroxyindole-2-carboxylate. Ref.32 Ref.34
Subunit structure	Homotrimer. Interacts with CXCR2 extracellular domain By similarity. Interacts with the CD74 extracellular domain, COPS5 and BNIPL. Ref.18 Ref.21 Ref.22 Ref.25 Ref.33 Ref.34
Subcellular location	Secreted. 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. Ref.1 Ref.2 Ref.18 Ref.23 Ref.25
Induction	Up-regulated in concanavalin-A-treated lymphocytes. Up-regulated in macrophages upon exposure to M.tuberculosis antigens. Ref.1 Ref.23
Involvement in 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. Note: Disease susceptibility is associated with variations 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.
Sequence similarities	Belongs to the MIF family.
Biophysicochemical properties	Kinetic parameters: KM=249 µM for phenylpyruvate Ref.20 KM=168 µM for p-hydroxyphenylpyruvate Vmax=2113 µmol/min/mg enzyme toward phenylpyruvate Vmax=524 µmol/min/mg enzyme toward p-hydroxyphenylpyruvate

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cytoplasm Secreted
Molecular function	Cytokine Isomerase
PTM	Acetylation
Technical term	3D-structure 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 direct assay Ref.22. Source: UniProtKB cell surface receptor signaling pathway Inferred from direct assay Ref.22. Source: UniProtKB 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 direct assay PubMed 17045821. Source: BHF-UCL negative regulation of apoptotic process Inferred from direct assay Ref.22. Source: UniProtKB negative regulation of cell aging Inferred from direct assay PubMed 10562313. Source: BHF-UCL negative regulation of cell cycle arrest Inferred from direct assay PubMed 10562313. Source: BHF-UCL negative regulation of cellular protein metabolic process Inferred from electronic annotation. Source: Compara negative regulation of gene expression Inferred from direct assay PubMed 10562313. Source: BHF-UCL 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 direct assay Ref.22. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from direct assay Ref.22PubMed 17045821. Source: BHF-UCL 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 direct assay PubMed 19602265. Source: BHF-UCL positive regulation of fibroblast proliferation Inferred from direct assay Ref.22. Source: BHF-UCL 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 direct assay PubMed 17045821. Source: BHF-UCL positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 17045821. Source: BHF-UCL 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 direct assay PubMed 17045821. Source: BHF-UCL prostaglandin biosynthetic process Inferred from direct assay Ref.22. Source: UniProtKB protein homotrimerization Inferred from physical interaction Ref.33. Source: UniProtKB regulation of macrophage activation Non-traceable author statement Ref.22. Source: UniProtKB
Cellular_component	cell surface Inferred from direct assay Ref.22. Source: BHF-UCL cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from direct assay Ref.22. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cell surface binding Inferred from direct assay Ref.22. Source: BHF-UCL chemoattractant activity Inferred from direct assay PubMed 19602265. Source: BHF-UCL cytokine activity Inferred from direct assay Ref.22. Source: UniProtKB dopachrome isomerase activity Inferred from direct assay Ref.33. Source: UniProtKB phenylpyruvate tautomerase activity Inferred from direct assay PubMed 16285950. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2L11	O43521-2	5	EBI-372712,EBI-526420

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.14 Ref.15

Chain

2 – 115

114

Macrophage migration inhibitory factor

PRO_0000158062

Sites

Active site

2

1

Proton acceptor; via imino nitrogen

Binding site

33

1

Substrate

Binding site

65

1

Substrate; via amide nitrogen

Binding site

98

1

Substrate

Amino acid modifications

Modified residue

78

1

N6-acetyllysine Ref.26

Experimental info

Sequence conflict

57 – 59

3

CAL → WAF in ABQ95571. Ref.6

Sequence conflict

67

1

K → R in CAG46452. Ref.9

Sequence conflict

79

1

L → Q in CAG46452. Ref.9

Sequence conflict

81

1

C → F in ABQ95571. Ref.6

Sequence conflict

106

1

N → S in AAA36315. Ref.1

Sequence conflict

113

1

T → P in ABQ95571. Ref.6

Secondary structure

1

.

.

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.

.

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.

.

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115

Helix Strand Turn

Details...

Beta strand

3 – 10

8

Helix

12 – 14

3

Helix

19 – 31

13

Helix

35 – 37

3

Beta strand

39 – 43

5

Beta strand

47 – 50

4

Beta strand

58 – 66

9

Helix

70 – 88

19

Helix

92 – 94

3

Beta strand

95 – 101

7

Helix

104 – 106

3

Beta strand

107 – 109

3

Beta strand

112 – 114

3

Sequences

	Sequence		Length	Mass (Da)
	P14174 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 56D51107C05286B2	FASTA	115	12,476
	10 20 30 40 50 60 MPMFIVNTNV PRASVPDGFL SELTQQLAQA TGKPPQYIAV HVVPDQLMAF GGSSEPCALC 70 80 90 100 110 SLHSIGKIGG AQNRSYSKLL CGLLAERLRI SPDRVYINYY DMNAANVGWN NSTFA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor." Weiser W.Y., Temple P.A., Witek-Giannotti J.S., Remold H.G., Clark S.C., David J.R. Proc. Natl. Acad. Sci. U.S.A. 86:7522-7526(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, SUBCELLULAR LOCATION.
[2]	"Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor." Mikayama T., Nakano T., Gomi H., Nakagawa Y., Liu Y.C., Iwamatsu A., Weiser W.Y., Ishizaka K., Sato M., Ishii Y. Proc. Natl. Acad. Sci. U.S.A. 90:10056-10060(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[3]	"Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF)." Bernhagen J., Mitchell R.A., Calandra T., Voelter W., Cerami A., Bucala R. Biochemistry 33:14144-14155(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning the human gene for macrophage migration inhibitory factor (MIF)." Paralkar V., Wistow G.J. Genomics 19:48-51(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The effect of macrophage migration inhibitory factor in the atherogenesis process." Shan Z.X., Yu X.Y., Lin S.G., Lin Q.X., Fu Y.H., Tan H.H. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Amplification and expression of macrophage migration inhibitory factor (MIF) in tissue of squamous carcinoma of the cervix." Wu S.H., Xie J., Shang H.X., Li Y., Zhang Z. Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[9]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[12]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung, Skin and Uterus.
[14]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-12. Tissue: Platelet.
[15]	"Human liver protein map: a reference database established by microsequencing and gel comparison." Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J. Electrophoresis 13:992-1001(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-11. Tissue: Liver.
[16]	"The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor." Zeng F.Y., Weiser W.Y., Kratzin H., Stahl B., Karas M., Gabius H.J. Arch. Biochem. Biophys. 303:74-80(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 3-24.
[17]	"A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens." Wistow G.J., Shaughnessy M., Lee D.C., Hodin J., Zelenka P.S. Proc. Natl. Acad. Sci. U.S.A. 90:1272-1275(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-115. Tissue: Lens.
[18]	"Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1." Kleemann R., Hausser A., Geiger G., Mischke R., Burger-Kentischer A., Flieger O., Johannes F.-J., Roger T., Calandra T., Kapurniotu A., Grell M., Finkelmeier D., Brunner H., Bernhagen J. Nature 408:211-216(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COPS5, SUBCELLULAR LOCATION.
[19]	"A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis." The British peadiatric rheumatology study group Donn R.P., Shelley E., Ollier W.E.R., Thomson W. Arthritis Rheum. 44:1782-1785(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS.
[20]	"Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis." Tan T.H.P., Edgerton S.A.V., Kumari R., McAlister M.S.B., Roe S.M., Nagl S., Pearl L.H., Selkirk M.E., Bianco A.E., Totty N.F., Engwerda C., Gray C.A., Meyer D.J., Rowe S.M. Biochem. J. 357:373-383(2001) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[21]	"The apoptosis-associated protein BNIPL interacts with two cell proliferation-related proteins, MIF and GFER." Shen L., Hu J., Lu H., Wu M., Qin W., Wan D., Li Y.-Y., Gu J. FEBS Lett. 540:86-90(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BNIPL.
[22]	"MIF signal transduction initiated by binding to CD74." Leng L., Metz C.N., Fang Y., Xu J., Donnelly S., Baugh J., Delohery T., Chen Y., Mitchell R.A., Bucala R. J. Exp. Med. 197:1467-1476(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD74.
[23]	"Macrophage migration inhibitory factor reduces the growth of virulent Mycobacterium tuberculosis in human macrophages." Oddo M., Calandra T., Bucala R., Meylan P.R.A. Infect. Immun. 73:3783-3786(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
[24]	"Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis." Emonts M., Sweep F.C.G.J., Grebenchtchikov N., Geurts-Moespot A., Knaup M., Chanson A.L., Erard V., Renner P., Hermans P.W.M., Hazelzet J.A., Calandra T. Clin. Infect. Dis. 44:1321-1328(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN SEPSIS-RELATED DEATH.
[25]	"The Golgi-associated protein p115 mediates the secretion of macrophage migration inhibitory factor." Merk M., Baugh J., Zierow S., Leng L., Pal U., Lee S.J., Ebert A.D., Mizue Y., Trent J.O., Mitchell R., Nickel W., Kavathas P.B., Bernhagen J., Bucala R. J. Immunol. 182:6896-6906(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH USO1.
[26]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-78, MASS SPECTROMETRY.
[27]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"Crystal structure of macrophage migration inhibitory factor from human lymphocyte at 2.1-A resolution." Sugimoto H., Suzuki M., Nakagawa A., Tanaka I., Nishihira J. FEBS Lett. 389:145-148(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[29]	"The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets." Kato Y., Muto T., Tomura T., Tsumura H., Watarai H., Mikayama T., Ishizaka K., Kuroki R. Proc. Natl. Acad. Sci. U.S.A. 93:3007-3010(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[30]	"Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor." Sun H.W., Bernhagen J., Bucala R., Lolis E. Proc. Natl. Acad. Sci. U.S.A. 93:5191-5196(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[31]	"Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity." Lubetsky J.B., Swope M., Dealwis C., Blake P., Lolis E. Biochemistry 38:7346-7354(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[32]	"Coumarin and chromen-4-one analogues as tautomerase inhibitors of macrophage migration inhibitory factor: discovery and X-ray crystallography." Orita M., Yamamoto S., Katayama N., Aoki M., Takayama K., Yamagiwa Y., Seki N., Suzuki H., Kurihara H., Sakashita H., Takeuchi M., Fujita S., Yamada T., Tanaka A. J. Med. Chem. 44:540-547(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH TAUTOMERASE INHIBITOR, CATALYTIC ACTIVITY.
[33]	"Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor." Crichlow G.V., Cheng K.F., Dabideen D., Ochani M., Aljabari B., Pavlov V.A., Miller E.J., Lolis E., Al-Abed Y. J. Biol. Chem. 282:23089-23095(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH CARBONYLOXIME-BASED INHIBITORS, SUBUNIT.
[34]	"Structural and kinetic analyses of macrophage migration inhibitory factor active site interactions." Crichlow G.V., Lubetsky J.B., Leng L., Bucala R., Lolis E.J. Biochemistry 48:132-139(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR N-ACETYL-P-BENZOQUINONE IMINE, SUBUNIT, CATALYTIC ACTIVITY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M25639 mRNA. Translation: AAA36315.1.
L10612 mRNA. Translation: AAA35892.1.
Z23063 mRNA. Translation: CAA80598.1.
L19686 Genomic DNA. Translation: AAA21814.1.
AF469046 mRNA. Translation: AAL78635.1.
EF611126 mRNA. Translation: ABQ95571.1.
CR456520 mRNA. Translation: CAG30406.1.
AK311929 mRNA. Translation: BAG34870.1.
CR407644 mRNA. Translation: CAG28572.1.
CR541651 mRNA. Translation: CAG46452.1.
BT007148 mRNA. Translation: AAP35812.1.
DQ307455 Genomic DNA. Translation: ABB96245.1.
CH471095 Genomic DNA. Translation: EAW59620.1.
BC000447 mRNA. Translation: AAH00447.1.
BC007676 mRNA. Translation: AAH07676.1.
BC008914 mRNA. Translation: AAH08914.1.
BC013976 mRNA. Translation: AAH13976.1.
BC022414 mRNA. Translation: AAH22414.1.
BC053376 mRNA. Translation: AAH53376.1.
M95775 mRNA. Translation: AAA36179.1.

IPI

IPI00293276.

PIR

A48793.

RefSeq

NP_002406.1. NM_002415.1.

UniGene

Hs.407995.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CA7	X-ray	2.50	A/B/C	2-115	[»]
1CGQ	X-ray	2.00	A/B/C	3-115	[»]
1GCZ	X-ray	1.90	A/B/C	2-115	[»]
1GD0	X-ray	1.50	A/B/C	2-115	[»]
1GIF	X-ray	1.90	A/B/C	1-115	[»]
1LJT	X-ray	2.00	A/B/C	2-114	[»]
1MIF	X-ray	2.60	A/B/C	1-115	[»]
1P1G	X-ray	2.50	A/B/C	3-115	[»]
2OOH	X-ray	1.85	A/B/C	2-115	[»]
2OOW	X-ray	1.75	A/B/C	2-115	[»]
2OOZ	X-ray	1.80	A/B/C	2-115	[»]
3B9S	X-ray	1.80	A/B/C	2-115	[»]
3CE4	X-ray	1.55	A/B/C	2-115	[»]
3DJH	X-ray	1.25	A/B/C	2-115	[»]
3DJI	X-ray	1.95	A/B/C/D/E/F	2-115	[»]
3HOF	X-ray	1.90	A/B/C	1-115	[»]
3IJG	X-ray	1.70	A/B/C	2-115	[»]
3IJJ	X-ray	1.25	A/B/C	2-115	[»]
3JSF	X-ray	1.93	A/B/C	2-115	[»]
3JSG	X-ray	1.58	A/B/C	2-115	[»]
3JTU	X-ray	1.86	A/B/C	2-115	[»]
3L5P	X-ray	1.80	A/B/C	2-115	[»]
3L5R	X-ray	1.94	A/B/C	2-115	[»]
3L5S	X-ray	1.86	A/B/C	2-115	[»]
3L5T	X-ray	1.86	A/B/C	2-115	[»]
3L5U	X-ray	1.90	A/B/C	2-115	[»]
3L5V	X-ray	1.70	A/B/C	2-115	[»]
3SMB	X-ray	1.60	A/B/C	2-115	[»]
3SMC	X-ray	1.80	A/B/C	2-115	[»]
3U18	X-ray	1.90	A/B/C	2-115	[»]
4ETG	X-ray	1.61	A/B/C	2-115	[»]
4EUI	X-ray	1.70	A/B/C	2-115	[»]
4EVG	X-ray	1.70	A/B/C	2-115	[»]
4F2K	X-ray	1.53	A/B/C	2-115	[»]

ProteinModelPortal

P14174.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31137N.

IntAct

P14174. 16 interactions.

MINT

MINT-5000040.

STRING

9606.ENSP00000215754.

PTM databases

PhosphoSite

P14174.

Polymorphism databases

DMDM

1170955.

2D gel databases

SWISS-2DPAGE

P14174.

Proteomic databases

PaxDb

P14174.

PeptideAtlas

P14174.

PRIDE

P14174.

Protocols and materials databases

DNASU

4282.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000215754; ENSP00000215754; ENSG00000240972.

GeneID

4282.

KEGG

hsa:4282.

UCSC

uc002zyr.1. human.

Organism-specific databases

CTD

4282.

GeneCards

GC22P024236.

H-InvDB

HIX0041297.

HGNC

HGNC:7097. MIF.

HPA

CAB005284.
HPA003868.

MIM

153620. gene.
604302. phenotype.

neXtProt

NX_P14174.

Orphanet

85414. Systemic-onset juvenile idiopathic arthritis.

PharmGKB

PA30819.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG08790.

HOGENOM

HOG000112325.

HOVERGEN

HBG003240.

InParanoid

P14174.

KO

K07253.

OMA

PDRIYIN.

OrthoDB

EOG49GKJ5.

PhylomeDB

P14174.

Gene expression databases

Bgee

P14174.

CleanEx

HS_MIF.

Genevestigator

P14174.

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

BindingDB

P14174.

ChEMBL

CHEMBL2085.

EvolutionaryTrace

P14174.

GenomeRNAi

4282.

NextBio

16845.

SOURCE

Search...

Entry information

Entry name

MIF_HUMAN

Accession

Primary (citable) accession number: P14174
Secondary accession number(s): A5Z1R8 , B2R4S3, Q2V4Y5, Q6FHV0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 161 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.