CPLM-004208

Genbank Nucleotide ID

Macrophage migration inhibitory factor

Protein Synonyms/Alias

MIF; Glycosylation-inhibiting factor; GIF; L-dopachrome isomerase; L-dopachrome tautomerase; Phenylpyruvate tautomerase

Homo sapiens (Human)

Position	Peptide	Type	References
78	AQNRSYSKLLCGLLA	acetylation	[1, 2, 3, 4, 5]
78	AQNRSYSKLLCGLLA	phosphoglycerylation	[6]
78	AQNRSYSKLLCGLLA	ubiquitination	[5, 7, 8, 9, 10, 11, 12, 13]

[1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[2] Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.
Marimuthu S, Chivukula RS, Alfonso LF, Moridani M, Hagen FK, Bhat GJ.
Int J Oncol. 2011 Nov;39(5):1273-83. [PMID: 21743961]
[3] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
[4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]
[5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[6] Functional lysine modification by an intrinsically reactive primary glycolytic metabolite.
Moellering RE, Cravatt BF.
Science. 2013 Aug 2;341(6145):549-53. [PMID: 23908237]
[7] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[8] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[9] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[11] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[12] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[13] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]

Functional Description

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.

ACT_SITE 2 2 Proton acceptor; via imino nitrogen.
BINDING 33 33 Substrate.
BINDING 65 65 Substrate; via amide nitrogen.
BINDING 98 98 Substrate.
MOD_RES 78 78 N6-acetyllysine.

3D-structure; Acetylation; Complete proteome; Cytokine; Cytoplasm; Direct protein sequencing; Immunity; Inflammatory response; Innate immunity; Isomerase; Reference proteome; Secreted.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0009986; C:cell surface; IDA:BHF-UCL.
GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO:0005576; C:extracellular region; IDA:UniProtKB.
GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
GO:0042056; F:chemoattractant activity; IDA:BHF-UCL.
GO:0005125; F:cytokine activity; IDA:UniProtKB.
GO:0004167; F:dopachrome isomerase activity; IDA:UniProtKB.
GO:0050178; F:phenylpyruvate tautomerase activity; IDA:MGI.
GO:0007569; P:cell aging; IEA:Compara.
GO:0008283; P:cell proliferation; IDA:UniProtKB.
GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB.
GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IEA:Compara.
GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
GO:0090344; P:negative regulation of cell aging; IDA:BHF-UCL.
GO:0071157; P:negative regulation of cell cycle arrest; IDA:BHF-UCL.
GO:0032269; P:negative regulation of cellular protein metabolic process; IEA:Compara.
GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
GO:0002906; P:negative regulation of mature B cell apoptotic process; IEA:Compara.
GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Compara.
GO:0090238; P:positive regulation of arachidonic acid secretion; IEA:Compara.
GO:0030890; P:positive regulation of B cell proliferation; IDA:BHF-UCL.
GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Compara.
GO:0050715; P:positive regulation of cytokine secretion; IDA:BHF-UCL.
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
GO:0048146; P:positive regulation of fibroblast proliferation; IDA:BHF-UCL.
GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IEA:Compara.
GO:0043406; P:positive regulation of MAP kinase activity; IEA:Compara.
GO:0061081; P:positive regulation of myeloid leukocyte cytokine production involved in immune response; IEA:Compara.
GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
GO:0061078; P:positive regulation of prostaglandin secretion involved in immune response; IEA:Compara.
GO:0010739; P:positive regulation of protein kinase A signaling cascade; IDA:BHF-UCL.
GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
GO:0070207; P:protein homotrimerization; IPI:UniProtKB.
GO:0043030; P:regulation of macrophage activation; NAS:UniProtKB.

IPR001398; Macrophage_inhib_fac.
IPR019829; Macrophage_inhib_fac_CS.
IPR014347; Tautomerase/MIF_sf.