Macrophage migration inhibitory factor (MIF) family proteins

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Macrophage migration inhibitory factor (MIF) family proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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This is a small protein family with 3 paralogs in the human genome:
D-dopachrome tautomerase like (DDTL)
Macrophage migration inhibitory factor (MIF; curated as ligand macrophage migration inhibitory factor (MIF, P14174))
D-dopachrome tautomerase (DDT)

MIF and DDT have been shown to have cytokine activity [4,7].

Enzymes

3342

D-dopachrome tautomerase Show summary »« Hide summary

Target Id

3342

Nomenclature

D-dopachrome tautomerase

Previous and unofficial names

D-dopachrome decarboxylase | macrophage migration inhibitory factor-2 (MIF2)

Genes

DDT (Hs), Ddt (Mm), Ddt (Rn)

Ensembl ID

ENSG00000099977 (Hs), ENSMUSG00000001666 (Mm), ENSRNOG00000083406 (Rn)

UniProtKB AC

P30046 (Hs), O35215 (Mm), P80254 (Rn)

EC number

4.1.1.84

Inhibitors

compound 10b [PMID: 41766566] pIC₅₀ 5.8 [8]

Comment

D-dopachrome tautomerase (DDT) has cytokine-like activity, acting as a macrophage migration inhibitory factor (MIF, P14174) homologue [3-4]. The active protein is an approximately 38 kDa homotrimer that catalyzes the keto-enol tautomerization of 4-hydroxyphenylpyruvate (4-HPP). DDT is implicated in tumorigenesis [5-6] and inflammation, and is being pursued as a drug target [1-2].

References

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1. Cavalli E, Ciurleo R, Petralia MC, Fagone P, Bella R, Mangano K, Nicoletti F, Bramanti P, Basile MS. (2020) Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?. Molecules, 25 (5). [PMID:32155795]

2. Jarmula J, Lee J, Lauko A, Rajappa P, Grabowski MM, Dhawan A, Chen P, Bucala R, Vogelbaum MA, Lathia JD. (2024) Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review. Neurooncol Adv, 6 (1): vdae142. [PMID:39233830]

3. Merk M, Mitchell RA, Endres S, Bucala R. (2012) D-dopachrome tautomerase (D-DT or MIF-2): doubling the MIF cytokine family. Cytokine, 59 (1): 10-7. [PMID:22507380]

4. Merk M, Zierow S, Leng L, Das R, Du X, Schulte W, Fan J, Lue H, Chen Y, Xiong H et al.. (2011) The D-dopachrome tautomerase (DDT) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF). Proc Natl Acad Sci U S A, 108 (34): E577-85. [PMID:21817065]

5. Mora Barthelmess R, Stijlemans B, Van Ginderachter JA. (2023) Hallmarks of Cancer Affected by the MIF Cytokine Family. Cancers (Basel), 15 (2). [PMID:36672343]

6. Pasupuleti V, Du W, Gupta Y, Yeh IJ, Montano M, Magi-Galuzzi C, Welford SM. (2014) Dysregulated D-dopachrome tautomerase, a hypoxia-inducible factor-dependent gene, cooperates with macrophage migration inhibitory factor in renal tumorigenesis. J Biol Chem, 289 (6): 3713-23. [PMID:24356968]

7. Song S, Xiao Z, Dekker FJ, Poelarends GJ, Melgert BN. (2022) Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury. Cell Mol Life Sci, 79 (2): 105. [PMID:35091838]

8. Wu Z, Widjaja V, Skeens E, van der Velde JJH, Zahran M, Zhang J, Cool RH, Poelarends GJ, Lisi GP, Dekker FJ. (2026) Discovery of Furan-2-Carboxylic Acid Derivatives as Novel D-Dopachrome Tautomerase (D-DT) and Macrophage Migration Inhibitory Factor-1 (MIF-1) Dual Inhibitors. J Med Chem, [Epub ahead of print]. [PMID:41766566]

How to cite this family page

Database page citation:

Macrophage migration inhibitory factor (MIF) family proteins. Accessed on 13/03/2026. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1126.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.