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Protein

Macrophage migration inhibitory factor

Gene

Mif

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

Keto-phenylpyruvate = enol-phenylpyruvate.
L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2Proton acceptor; via imino nitrogenBy similarity1
Binding sitei33SubstrateBy similarity1
Binding sitei65Substrate; via amide nitrogenBy similarity1
Binding sitei98SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • brain development Source: RGD
  • brain renin-angiotensin system Source: RGD
  • cellular response to hydrogen peroxide Source: RGD
  • cellular response to hypoxia Source: RGD
  • drinking behavior Source: RGD
  • hair follicle development Source: RGD
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • positive regulation of acute inflammatory response Source: RGD
  • positive regulation of axon regeneration Source: RGD
  • positive regulation of glucose import Source: RGD
  • positive regulation of glycolytic process Source: RGD
  • positive regulation of immune response Source: RGD
  • positive regulation of potassium ion transport Source: RGD
  • positive regulation of smooth muscle cell migration Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to glucocorticoid Source: RGD
  • response to heat Source: RGD
  • response to hormone Source: RGD
  • response to inorganic substance Source: RGD
  • response to insulin Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to menaquinone Source: RGD
  • response to progesterone Source: RGD
  • response to vitamin E Source: RGD
  • skin development Source: RGD
  • spermatogenesis Source: RGD
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Isomerase

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-RNO-202733. Cell surface interactions at the vascular wall.
R-RNO-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage migration inhibitory factor (EC:5.3.2.1)
Short name:
MIF
Alternative name(s):
Glutathione-binding 13 kDa protein
L-dopachrome isomerase
L-dopachrome tautomerase (EC:5.3.3.12)
Phenylpyruvate tautomerase
Gene namesi
Name:Mif
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi621163. Mif.

Subcellular locationi

  • Secreted By similarity
  • Cytoplasm By similarity

  • 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 (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: RGD
  • extracellular space Source: RGD
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001580682 – 115Macrophage migration inhibitory factorAdd BLAST114

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78N6-acetyllysine; alternateBy similarity1
Modified residuei78N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP30904.
PRIDEiP30904.

PTM databases

iPTMnetiP30904.
PhosphoSitePlusiP30904.

Expressioni

Tissue specificityi

Expressed in a wide variety of organs including brain, spleen, liver, muscle and kidney.

Gene expression databases

BgeeiENSRNOG00000006589.
ExpressionAtlasiP30904. baseline.
GenevisibleiP30904. RN.

Interactioni

Subunit structurei

Homotrimer. Interacts with BNIPL (By similarity). Interacts with the CD74 extracellular domain. Interacts with COPS5 and with the CXCR2 extracellular domain (By similarity).By similarity

GO - Molecular functioni

  • protein complex binding Source: RGD

Protein-protein interaction databases

IntActiP30904. 3 interactors.
MINTiMINT-4590553.
STRINGi10116.ENSRNOP00000008608.

Structurei

Secondary structure

1115
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 8Combined sources6
Helixi12 – 14Combined sources3
Helixi19 – 31Combined sources13
Helixi35 – 37Combined sources3
Beta strandi39 – 43Combined sources5
Beta strandi58 – 66Combined sources9
Helixi70 – 88Combined sources19
Helixi92 – 94Combined sources3
Beta strandi95 – 102Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FIMX-ray2.20A2-115[»]
ProteinModelPortaliP30904.
SMRiP30904.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30904.

Family & Domainsi

Sequence similaritiesi

Belongs to the MIF family.Curated

Phylogenomic databases

eggNOGiKOG1759. Eukaryota.
ENOG41122MF. LUCA.
GeneTreeiENSGT00840000129866.
HOGENOMiHOG000112325.
HOVERGENiHBG003240.
InParanoidiP30904.
KOiK07253.
OMAiKFYDSPR.
OrthoDBiEOG091G0ZNJ.
PhylomeDBiP30904.
TreeFamiTF313853.

Family and domain databases

InterProiIPR001398. Macrophage_inhib_fac.
IPR019829. Macrophage_inhib_fac_CS.
IPR014347. Tautomerase/MIF_sf.
[Graphical view]
PANTHERiPTHR11954. PTHR11954. 1 hit.
PfamiPF01187. MIF. 1 hit.
[Graphical view]
ProDomiPD004816. Macrophage_inhib_fac. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF55331. SSF55331. 1 hit.
PROSITEiPS01158. MIF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P30904-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPMFIVNTNV PRASVPEGFL SELTQQLAQA TGKPAQYIAV HVVPDQLMTF
60 70 80 90 100
SGTSDPCALC SLHSIGKIGG AQNRNYSKLL CGLLSDRLHI SPDRVYINYY
110
DMNAANVGWN GSTFA
Length:115
Mass (Da):12,477
Last modified:January 23, 2007 - v4
Checksum:i8333F7B81B098445
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51S → R in AAA62644 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73424 mRNA. Translation: AAB32392.1.
U20999 mRNA. Translation: AAA62644.1.
U62326 mRNA. Translation: AAB04024.1.
BC061545 mRNA. Translation: AAH61545.1.
PIRiS27117.
RefSeqiNP_112313.1. NM_031051.1.
XP_008772068.1. XM_008773846.2.
XP_017457271.1. XM_017601782.1.
UniGeneiRn.2661.

Genome annotation databases

EnsembliENSRNOT00000008608; ENSRNOP00000008608; ENSRNOG00000006589.
ENSRNOT00000077564; ENSRNOP00000074316; ENSRNOG00000056076.
GeneIDi103694877.
81683.
KEGGirno:103694877.
rno:81683.
UCSCiRGD:621163. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73424 mRNA. Translation: AAB32392.1.
U20999 mRNA. Translation: AAA62644.1.
U62326 mRNA. Translation: AAB04024.1.
BC061545 mRNA. Translation: AAH61545.1.
PIRiS27117.
RefSeqiNP_112313.1. NM_031051.1.
XP_008772068.1. XM_008773846.2.
XP_017457271.1. XM_017601782.1.
UniGeneiRn.2661.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FIMX-ray2.20A2-115[»]
ProteinModelPortaliP30904.
SMRiP30904.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP30904. 3 interactors.
MINTiMINT-4590553.
STRINGi10116.ENSRNOP00000008608.

PTM databases

iPTMnetiP30904.
PhosphoSitePlusiP30904.

Proteomic databases

PaxDbiP30904.
PRIDEiP30904.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008608; ENSRNOP00000008608; ENSRNOG00000006589.
ENSRNOT00000077564; ENSRNOP00000074316; ENSRNOG00000056076.
GeneIDi103694877.
81683.
KEGGirno:103694877.
rno:81683.
UCSCiRGD:621163. rat.

Organism-specific databases

CTDi4282.
RGDi621163. Mif.

Phylogenomic databases

eggNOGiKOG1759. Eukaryota.
ENOG41122MF. LUCA.
GeneTreeiENSGT00840000129866.
HOGENOMiHOG000112325.
HOVERGENiHBG003240.
InParanoidiP30904.
KOiK07253.
OMAiKFYDSPR.
OrthoDBiEOG091G0ZNJ.
PhylomeDBiP30904.
TreeFamiTF313853.

Enzyme and pathway databases

ReactomeiR-RNO-202733. Cell surface interactions at the vascular wall.
R-RNO-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiP30904.
PROiP30904.

Gene expression databases

BgeeiENSRNOG00000006589.
ExpressionAtlasiP30904. baseline.
GenevisibleiP30904. RN.

Family and domain databases

InterProiIPR001398. Macrophage_inhib_fac.
IPR019829. Macrophage_inhib_fac_CS.
IPR014347. Tautomerase/MIF_sf.
[Graphical view]
PANTHERiPTHR11954. PTHR11954. 1 hit.
PfamiPF01187. MIF. 1 hit.
[Graphical view]
ProDomiPD004816. Macrophage_inhib_fac. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF55331. SSF55331. 1 hit.
PROSITEiPS01158. MIF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMIF_RAT
AccessioniPrimary (citable) accession number: P30904
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 146 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.