Reviewed, UniProtKB/Swiss-Prot P14174 (MIF_HUMAN)

Names and origin

Protein names

Recommended name:
    Macrophage migration inhibitory factor
      Short name=MIF
    EC=5.3.2.1
Alternative name(s):
    Phenylpyruvate tautomerase
    Glycosylation-inhibiting factor
      Short name=GIF

Gene names

Name:	MIF
Synonyms:	GLIF, MMIF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	The expression of MIF at sites of inflammation suggest a role for the mediator in regulating the function of macrophage in host defense. Also acts as a phenylpyruvate tautomerase.
Catalytic activity	Keto-phenylpyruvate = enol-phenylpyruvate.
Subunit structure	Homotrimer. Interacts with COPS5 and BNIPL. Ref.15 Ref.16
Involvement in disease	Genetic variations in MIF are associated with susceptibility to systemic juvenile rheumatoid arthritis [MIM:604302]. Systemic juvenile rheumatoid arthritis is juvenile chronic arthritis associated with severe, debilitating, extraarticular features, and occasionally fatal complications. Despite medical treatment, many children still experience early joint destruction, necessitating surgical replacement.
Sequence similarities	Belongs to the MIF family.

Ontologies

Keywords
Biological process	Inflammatory response
Molecular function	Cytokine Isomerase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell proliferation Inferred from direct assay. Source: UniProtKB cell surface receptor linked signal transduction Inferred from direct assay. Source: UniProtKB inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptosis Inferred from direct assay. Source: UniProtKB prostaglandin biosynthetic process Inferred from direct assay. Source: UniProtKB regulation of macrophage activation Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from direct assay. Source: UniProtKB phenylpyruvate tautomerase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2L11	O43521-1	1	EBI-372712,EBI-526416
BCL2L11	O43521-2	5	EBI-372712,EBI-526420
BCL2L11	O43521-3	1	EBI-372712,EBI-2123748
DSTYK	Q6XUX3	1	EBI-372712,EBI-1049520
FIBP	O43427	1	EBI-372712,EBI-724809
TNFRSF10D	Q9UBN6	1	EBI-372712,EBI-1044859
ZNF408	Q9H9D4	1	EBI-372712,EBI-347633

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.12 Ref.14

Chain

2 – 115

114

Macrophage migration inhibitory factor

PRO_0000158062

Sites

Active site

2

1

Proton acceptor; via imino nitrogen

Amino acid modifications

Modified residue

37

1

Phosphotyrosine Ref.17

Experimental info

Sequence conflict

106

1

N → S in AAA36315. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

115

Helix Strand Turn

Details...

Beta strand

3 – 10

8

Helix

12 – 14

3

Helix

19 – 31

13

Helix

35 – 37

3

Beta strand

38 – 43

6

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

Sequences

	Sequence		Length	Mass (Da)
	P14174-1 [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: 2552447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 8234256] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning the human gene for macrophage migration inhibitory factor (MIF)." Paralkar V., Wistow G.J. Genomics 19:48-51(1994) [PubMed: 8188240] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 7947826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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]	"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:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"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].
[9]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung, Skin and Uterus.
[11]	"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: 7679497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-115. Tissue: Lens.
[12]	"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: 1286669] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-11. Tissue: Liver.
[13]	"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: 7683862] [Abstract] Cited for: PROTEIN SEQUENCE OF 3-24.
[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: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-12. Tissue: Platelet.
[15]	"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: 11089976] [Abstract] Cited for: INTERACTION WITH COPS5.
[16]	"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: 12681488] [Abstract] Cited for: INTERACTION WITH BNIPL.
[17]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-37, MASS SPECTROMETRY.
[18]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[19]	"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: 8766818] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[20]	"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: 8610159] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[21]	"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: 8643551] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[22]	"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: 10353846] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[23]	"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: 11508429] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

IPI

IPI00293276.

PIR

A48793.

RefSeq

NP_002406.1.

UniGene

Hs.407995

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P14174. 27 interactions.

PTM databases

PhosphoSite

P14174.

2-D gel databases

SWISS-2DPAGE

P14174.

Siena-2DPAGE

P14174.

Proteomic databases

PeptideAtlas

P14174.

PRIDE

P14174.

Genome annotation databases

Ensembl

ENSG00000099964. Homo sapiens. [Contig view]

GeneID

4282.

KEGG

hsa:4282.

Organism-specific databases

GeneCards

GC22P022561.

H-InvDB

HIX0016302.

HGNC

HGNC:7097. MIF.

HPA

CAB005284.
HPA003868.

MIM

153620. gene.
604302. phenotype.

Orphanet

92. Juvenile Idiopathic Arthritis.

PharmGKB

PA30819.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P14174.

HOVERGEN

P14174.

OMA

P14174. PDRIYIN.

Enzyme and pathway databases

BRENDA

5.3.2.1. 247.

Gene expression databases

ArrayExpress

P14174.

Bgee

P14174.

CleanEx

HS_MIF.

Family and domain databases

InterPro

IPR001398. Macrophage_inhib_fac.
IPR019829. Macrophage_inhib_fac_CS.
IPR014347. Tautomerase.
[Graphical view]

Gene3D

G3DSA:3.30.429.10. Tautomerase. 1 hit.

PANTHER

PTHR11954. MIF. 1 hit.

Pfam

PF01187. MIF. 1 hit.
[Graphical view]

ProDom

PD004816. MIF. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS01158. MIF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

16845.

SOURCE

Search...

Entry information

Entry name

MIF_HUMAN

Accession

Primary (citable) accession number: P14174
Secondary accession number(s): Q2V4Y5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 116 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)