Information on EC 5.3.3.12 - L-dopachrome isomerase

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY
5.3.3.12
-
RECOMMENDED NAME
GeneOntology No.
L-dopachrome isomerase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
L-dopachrome = 5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
-
L-dopachrome = 5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
intramolecular oxidoreduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
eumelanin biosynthesis
-
Metabolic pathways
-
Tyrosine metabolism
-
SYSTEMATIC NAME
IUBMB Comments
L-dopachrome keto-enol isomerase
A zinc enzyme. Stereospecific for L-dopachrome. Dopachrome methyl ester is a substrate, but dopaminochrome (2,3-dihydroindole-5,6-quinone) is not (see also EC 4.1.1.84, D-dopachrome decarboxylase).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
brown (b) locus protein
-
-
-
-
D-dopachrome tautomerase
-
-
D-dopachrome tautomerase
-
-
D-dopachrome tautomerase
P80254
-
DCF
-
-
-
-
DCT
-
-
-
-
DDT
P80254
-
dopachrome conversion factor
-
-
-
-
dopachrome delta-isomerase
-
-
-
-
dopachrome DELTA7-DELTA2-isomerase
-
-
-
-
dopachrome oxidoreductase
-
-
-
-
dopachrome tautomerase
-
-
-
-
dopachrome tautomerase
-
-
dopachrome tautomerase
-
melanogenic enzyme
dopachrome tautomerase
-
-
dopachrome tautomerase
-
-
dopachrome-rearranging enzyme
-
-
-
-
isomerase, dopachrome DELTA-
-
-
-
-
L-dopachchrome-methyl ester tautomerase
-
-
-
-
Macrophage migration inhibitory factor
-
-
macrophage migration-inhibitory factor
-
-
SLATY locus protein
-
-
-
-
TRP-2
-
melanogenic enzyme
TRP2
-
-
-
-
tyrosine-related protein 2
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
130122-81-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
different isoforms of enzyme
-
-
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
gene mif
-
-
Manually annotated by BRENDA team
newborn congenic C57BL/6J non-agouti black mice
-
-
Manually annotated by BRENDA team
recombinant enzyme Dct-lacZ fusion protein
-
-
Manually annotated by BRENDA team
no activity in Caenorhabditis elegans
-
-
-
Manually annotated by BRENDA team
no activity in Heligmosomoides polygyrus
-
-
-
Manually annotated by BRENDA team
no activity in Hymenolepis diminuta
-
-
-
Manually annotated by BRENDA team
no activity in Nippostrongylus brasiliensis
-
-
-
Manually annotated by BRENDA team
no activity in Schistosoma haematobium
-
-
-
Manually annotated by BRENDA team
no activity in Schistosoma japonicum
-
-
-
Manually annotated by BRENDA team
no activity in Schistosoma mansoni
-
-
-
Manually annotated by BRENDA team
black-boned sheep
-
-
Manually annotated by BRENDA team
male Wistar rats
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
MIF is implicated in the pathogenesis of several inflammatory and autoimmune diseases
malfunction
-
MIF expression contributes to cell proliferation, invasiveness and neo-angiogenesis of neuroblastoma, gastric, hepatocellular, bladder, and breast carcinomas. MIF takes part in the pathogenesis of Alzheimer's disease and multiple sklerosis
malfunction
-
Dct inactivation elevates the level of ROS, increases the numbers of sunburn cells and apoptotic cells, and decreases the amount of eumelanin in the epidermis upon exposure to chronic UVA radiation
malfunction
-
Dct inactivation in knockout mice exposed to UVA radiation elevates the level of reactive oxygen species, increases the number of sunburn cells and apoptotic cells and decreases the amount of eumelanin in the epidermis
physiological function
P80254
increase in D-dopachrome tautomerase is a response to liver damage, accelerates melanin biosynthesis and protects the liver from oxidative stress induced by CCl4, overview
physiological function
-
MIF is involved in diverse biological processes, e.g. MIF glucocorticoid overriding activity, endotoxin lipopolysaccharide-induced TNF production, MIF-mediated stimulation of ERK1/2 MAP kinase and proliferation of serum-starved cells, MIF-mediated upregulation of arachidonic acid in macrophages, and Cox-2 activation
physiological function
-
MIF plays an essential role in both, innate and adaptive immune response. It is implicated in tumor growth and angiogenesis, an exerts an antagonistic effect against glucocorticoid immunosuppressive action, and shows glucorticoid overriding activity
physiological function
-
Dct is a critical enzyme in the melanogenesis pathway. It is involved in regulation of DHICA-mediated antioxidation and protection of the skin against UVA radiation
physiological function
-
the enzyme is produced by NS0 cells as a factor to support proliferation, it is probably involved in autocrine regulation of proliferation, mechanism, overview
physiological function
-
MIF is an upstream regulator of innate immunity and a potential molecular link between inflammation and cancer, functional role of the MIF tautomerase activity in vivo, overview. MIF's intrinsic tautomerase activity is dispensable for this cytokine's growth-regulatory properties and support a role for the N-terminal region in protein-protein interactions
physiological function
-
DCT plays a critical role in lowering the oxidative stress resulting from melanogenesis
physiological function
-
Dct plays a role in the regulation of eumelanin antioxidant properties
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
highly stereospecific for L-dopachrome
-
?
dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
highly stereospecific for L-dopachrome, not: D-isomer
-
?
dopachrome
?
show the reaction diagram
-
melanin biosynthesis
-
-
?
L-3,4-dihydroxyphenylalanine methyl ester
methyl 3-(3,4-dioxocyclohexa-1,5-dien-1-yl)-L-alaninate
show the reaction diagram
-
i.e. L-3,4-dihydroxyphenylalanine methyl ester hydrochloride, the catalytic residue is N-terminal Pro1
-
-
r
L-3,4-dihydroxyphenylalanine methyl ester
methyl 3-(3,4-dioxocyclohexa-1,5-dien-1-yl)-L-alaninate
show the reaction diagram
-
the catalytic residue is N-terminal Pro1
-
-
r
L-alpha-methyldopachrome
5,6-dihydroxy-2-methyl-2,3-dihydro-1H-indole-2-carboxylic acid
show the reaction diagram
-
-
-
-
-
L-dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
-
?
L-dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
-
?
L-dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
Dct isomerizes the intermediate dopachrome to 5,6-dihydroxyindole-2-carboxylic acid, DHICA, and influences the proportion of DHICA monomer incorporated into the 5,6-dihydroxyindole, DHI, polymer in eumelanin
DHICA monomers are required to incorporate into the DHI polymer backbone of eumelanin. DHICA exhibits a potent hydroxyl radical-scavenging activity when bound to melanin, while DHI-melanin does not
-
?
L-dopachrome
5,6-dihydroindole-2-carboxylic acid
show the reaction diagram
-
i.e. 2-carboxy-2,3-dihydroindole-5,6-quinone, the enzyme is strictly specific for the L-enantiomer. The N-terminal Pro is crucial for tautomerase activity
-
-
?
additional information
?
-
-
no substrate: L-dopachrome methyl ester, dopaminochrome, adrenochrome
-
-
-
additional information
?
-
-
existence of a common mechanism underlying radio- and chemoresistance, which is mediated by the enzyme
-
-
-
additional information
?
-
-
role of enzyme in cytoprotection by preventing the production of atoxic melanin precursor, 5,6-dihydroxyindole
-
-
-
additional information
?
-
-
isoforms of enzyme may play a part in the normal pathway of melamin biosynthesis
-
-
-
additional information
?
-
-
structure-function relationship, overview
-
-
-
additional information
?
-
-
WM35-wild-type and WM35-C2 cells, containing overexpressed TRP-2 enzyme are incubated with various H2O2 concentrations to determine the survival rate. TRP-2 reduces oxidative stress-induced toxicity of WM35-C2 cells compared to the wild-type cells, at 300 microM H2O2 30% decrease of cell sensitivity. TRP-2 protects genomic DNA from oxidative stress damage: in wild-type WM35 cells the damaging effect on DNA is visible at 50 microM H2O2. WM35 cells containing the overexpressed TRP-2 show DNA damage after treatment with 100 microM H2O2. The overexpression of TRP-2 in HEK-293 cells shows no improvement of the cell sensitivity to oxidative stress
-
-
-
additional information
?
-
-
DCT interacts with melanin
-
-
-
additional information
?
-
-
MIF is a 12 kDa protein with an enzymatic keto-enol tautomerase activityMIF is a homotrimeric multifunctional proinflammatory cytokine. Binding of MIF to its receptor, CD74, overview
-
-
-
additional information
?
-
-
MIF is a homotrimeric multifunctional proinflammatory cytokine. Binding of MIF to its receptor, CD74, overview
-
-
-
additional information
?
-
-
the MIF protein is multifunctional, exhibiting besides its L-dopachrome tautomerase activity, e.g. also phenylpyruvate tautomerase activity, EC 5.3.2.1, and thioredoxin-like function, or its cytokine function, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
dopachrome
?
show the reaction diagram
-
melanin biosynthesis
-
-
?
L-dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
-
?
L-dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
-
-
-
?
L-dopachrome
5,6-dihydroxyindole-2-carboxylate
show the reaction diagram
-
Dct isomerizes the intermediate dopachrome to 5,6-dihydroxyindole-2-carboxylic acid, DHICA, and influences the proportion of DHICA monomer incorporated into the 5,6-dihydroxyindole, DHI, polymer in eumelanin
DHICA monomers are required to incorporate into the DHI polymer backbone of eumelanin. DHICA exhibits a potent hydroxyl radical-scavenging activity when bound to melanin, while DHI-melanin does not
-
?
additional information
?
-
-
existence of a common mechanism underlying radio- and chemoresistance, which is mediated by the enzyme
-
-
-
additional information
?
-
-
role of enzyme in cytoprotection by preventing the production of atoxic melanin precursor, 5,6-dihydroxyindole
-
-
-
additional information
?
-
-
isoforms of enzyme may play a part in the normal pathway of melamin biosynthesis
-
-
-
additional information
?
-
-
DCT interacts with melanin
-
-
-
additional information
?
-
-
MIF is a 12 kDa protein with an enzymatic keto-enol tautomerase activityMIF is a homotrimeric multifunctional proinflammatory cytokine. Binding of MIF to its receptor, CD74, overview
-
-
-
additional information
?
-
-
MIF is a homotrimeric multifunctional proinflammatory cytokine. Binding of MIF to its receptor, CD74, overview
-
-
-
additional information
?
-
-
the MIF protein is multifunctional, exhibiting besides its L-dopachrome tautomerase activity, e.g. also phenylpyruvate tautomerase activity, EC 5.3.2.1, and thioredoxin-like function, or its cytokine function, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Iron
-
metal-containing enzyme, possibly with iron at its catalytic center
Zinc
-
zinc protein, two metal-binding sites
Zinc
-
1.5 zinc atoms per protein molecule
Zinc
-
required
Iron
-
enzyme binds small amounts
additional information
-
metal-containing enzyme, possibly with iron at its catalytic center
additional information
-
not: copper
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
-
2,2'-dipyridyl
-
-
2,3-Dihydroxybenzoic acid
-
-
2-oxo-4-phenyl-3-butynoate
-
a potent site-directed irreversible inhibitor of the phenyl pyruvate tautomerase activity
2-piperidinoethyl isothiocyanate
-
-
3,6-dihydroxy-1-methyl-5-oxo-3,5-dihydro-2H-indolium
-
a dopachrome derivative, 98% inhibition at 0.5 mM, mechanism of action, overview
3,6-dihydroxy-2-methyl-2,3-dihydro-5H-indol-5-one
-
a dopachrome derivative, 92% inhibition at 0.5 mM, mechanism of action, overview
3,6-dihydroxy-5-oxo-3,5-dihydro-2H-indole-2-carboxylic acid
-
a dopachrome derivative, complete inhibition at 0.5 mM, mechanism of action, overview
6-hydroxy-2-methyl-5-oxo-3,5-dihydro-2H-indole-2-carboxylic acid
-
a dopachrome derivative, 35% inhibition at 0.5 mM, mechanism of action, overview; a dopachrome derivative, L-derivative, 29% inhibition at 0.5 mM, mechanism of action, overview
allyl isothiocyamate
-
-
Benzyl isothiocyanate
-
specific inhibition of MIF tautomerase activity is mediated by selective modification of the N-terminal proline
EDTA
-
Zn2+ restores activity
ethyl isothiocyanate
-
-
haematin
-
50% inhibition at 0.015 mM
haematin
-
50% inhibition at 0.0002 mM
haematin
-
50% inhibition at 0.015 mM
haematin
-
50% inhibition at 0.0026 mM
Isothiocyanate
-
inhibits tautomerase activity of MIF. Modification and inhibition of MIF is not involved in the induction of phase 2 gene expression in response to isothiocyanate treatment
methallyl isothiocyanate
-
-
phenethylisothiocyanate
-
inhibits tautomerase activity of MIF
sulforaphane
-
inhibits tautomerase activity of MIF
tryptophan
-
-
methyl 6-hydroxy-2-methyl-5-oxo-3,5-dihydro-2H-indole-2-carboxylate
-
a dopachrome derivative, 34% inhibition at 0.5 mM, mechanism of action, overview; a dopachrome derivative, 45% inhibition at 0.5 mM, mechanism of action, overview
additional information
-
unaffected by metal chelators
-
additional information
-
design and synthesis of irreversible isothiocyanate-based inhibitors of MIF, inhibitory potencies and inhibition mechanism, overview
-
additional information
-
there exist several classes of inhibitors that are active against MIF tautomerase activity, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
L-ascorbic acid
-
enzyme activity depends on the presence of a reducing compound to a final concentration of 0.1mM
N-acetyl-L-cysteine
-
enzyme activity depends on the presence of a reducing compound to a final concentration of 0.1mM
L-cysteine
-
enzyme activity depends on the presence of a reducing compound to a final concentration of 0.1mM
additional information
-
no stimulation by D-dopachrome
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.1
-
dopachrome
-
pH 6.0, 30°C
1
-
dopachrome
-
27°C, pH 6.8
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2
-
tryptophan
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0031
-
2-piperidinoethyl isothiocyanate
-
-
0.0037
-
allyl isothiocyamate
-
-
0.0008
-
Benzyl isothiocyanate
-
-
0.0111
-
ethyl isothiocyanate
-
-
0.0014
-
methallyl isothiocyanate
-
-
0.005
0.006
phenethylisothiocyanate
-
-
0.001
0.002
sulforaphane
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.8
8.2
-
pH 4.8: about 40% of maximum activity, pH 8.2: about 55% of maximum activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
measuring of the spatial and temporal pattern of enzyme expression in vivo during neocortical neurogenesis. Enzyme is expressed in all layers of the dorsal telencephalon in E10.5. At E15.5 and E17.5, expression is primarily localized to the ventricular zone. Blocking endogenous enzyme by RNAi decreases proliferation of embryoic cortical neural progenitor cells. In adult brain, strong expression is observed in rostral migratory stream and septum. Overexpression of enzyme in subventricular zone cells of adult mice significantly increases the number of cells, whereas silencing Dct enzyme by RNAi decreases the cell number
Manually annotated by BRENDA team
-
preparation of single-cell suspensions of the tail skin
Manually annotated by BRENDA team
-
Cloudman mouse melanoma cells
Manually annotated by BRENDA team
-
Cloudman mouse melanoma cells (S91)
Manually annotated by BRENDA team
-
of neural crest origin
Manually annotated by BRENDA team
-
melan-a, melan-b, melan-c melanocytes
Manually annotated by BRENDA team
-
WM35 cell line
Manually annotated by BRENDA team
-
levels of DCT are elevated in melanoma cell lines that are especially resistant to chemotherapy and radiation
Manually annotated by BRENDA team
-
peripheral blood mononuclear cells, expression in wild-type but no enzyme expression in vitiligo patients, overview
Manually annotated by BRENDA team
-
blocking endogenous enzyme by RNAi decreases proliferation of embryoic cortical neural progenitor cells
Manually annotated by BRENDA team
-
corticotrop cells
Manually annotated by BRENDA team
-
retinal pigment epithelium
Manually annotated by BRENDA team
-
strong expression in adult
Manually annotated by BRENDA team
-
strong expression in adult
Manually annotated by BRENDA team
-
a human melanotic melanoma cell line
Manually annotated by BRENDA team
-
overexpression of enzyme in subventricular zone cells of adult mice significantly increases the number of cells, whereas silencing Dct enzyme by RNAi decreases the cell number
Manually annotated by BRENDA team
-
enzyme is expressed in all layers of the dorsal telencephalon in E10.5
Manually annotated by BRENDA team
-
at E15.5 and E17.5, enzyme expression is primarily localized to the ventricular zone
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
preferentially associated to, but also found in microsomal and cytosolic fractions
Manually annotated by BRENDA team
-
DCT has a hydrophobic transmembrane anchor
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
300000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 46000, SDS-PAGE
trimer
-
trimer formation is required for MIF tautomerase activity, trimer three-dimensional structure and tautomerase active site structure. The subunit interface is not as hydrophobic as the interior of the monomer, however, there is a hydrophobic patch on the surface involving residues Y36, Y95, W108, and F113, MALDI-TOF and analytical gel filtration analysis, overview
trimer
-
the tertiary structure is stabilized by hydrogen bonds and a hydrophobic core, three beta-sheets and six alpha-helices surround a traversing channel with dominant positive charge in the middle of the trimer, structure, overview. The enzyme contains a Cys-Xaa-Xaa-Cys motif required for oxido-reductase activity and MIF-like activities like glucorticoid overriding and cell proliferation
?
-
x * 85000, SDS-PAGE
additional information
-
structure-function relationship, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
Analysis of DCT tryptic peptides by MALDI-TOF/TOF determines N-glycosylation as a primary post-translational modification
glycoprotein
-
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzymne from Sf9 insect cells by ammonium sulfate fractionation, hydroxyapatite and anion exchange chromatography, and gel filtration
-
recombinant MIF from Escherichia coli strain BL21(DE3) by anion exchange chromatography and gel filtration
-
immuno-affinity purification
-
partial
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli strain BL21(DE3)
-
expression of the truncated enzyme lacking its carboxy-terminal transmembrane region in Spodoptera frugiperda Sf9 insect cell using a viral transfer vector
-
genotyping of healthy and autoimmune vitiligo individuals, overview
-
overexpressed in WM35 melanoma cell line as model system, endogenously expressing low levels of TRP-2. TRP-2 specifically decreases WM35 cell sensitivity to oxidative stress. Overexpreesion of enzyme in HEK-293 cells has no influence on cell sensitivity to oxidative stress
-
recombinant expression of MIF in HeLa cells and in Escherichia coli strain BL21(DE3)
-
Dct genotyping
-
gene mif
-
DNA and amino acid sequence determination of the tyrosinase-related protein2/DOPAchrome tautomerase gene, polymorphism analysis, overview
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
MIF expression is upregulated by cytokines, TNF-alpha and interleukin-I, and by bacterial endotoxins, such as lipopolysaccharides, and exotoxins
-
carbon tetrachloride treatment of livers lead to a 12fold increased expression level of dopachrome tautomerase in male rats, proteomic analysis, overview. The increase in DDT is a response to liver damage, accelerates melanin biosynthesis and protects the liver from oxidative stress induced by CCl4
P80254
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
P1G
-
generation of knockout mice in which the endogenous mif gene is replaced by one encoding a tautomerase-null, Pro1-Gly1 MIF protein, i.e. P1G-MIF, which is P1G-MIF is catalytically completely inactive, but maintains significant, albeit reduced, binding to its cell surface receptor CD74 and to the intracellular binding protein JAB1/CSN5. Mutant mice show a phenotype in assays of growth control and tumor induction that is intermediate between those of the wild type mif+/+ and complete MIF deficiency mif-/-, overview. Reduced development of benzo[alpha]pyrene-induced skin tumors in mif-deficient mice
R194Q
-
slaty mutation, 3fold reduction in enzyme activity compared to wild-type. Increase in pheomelanin and reduction in eumelanin produced by melanocytes in culture
additional information
-
preparation of biotin-isothiocyanate-labeled enzyme, proteomic screening in recombinant HeLa cells and identification of the modification site by mass spectrometry
additional information
-
modification of Pro1, e.g. via isothiocyanate inhibitors, alters the tertiary, but not the secondary or quaternary, structure of the trimer without affecting its thermodynamic stability, overview
G486R
-
slaty light mutation, 28fold reduction in enzyme activity, sliding of transmembrane domain towards N-terminus of protein thus interfering with the active site. Increase in pheomelanin and reduction in eumelanin produced by melanocytes in culture
additional information
-
enzyme knockout mutant, animals are viable and do not show any abnormalities in skin, retinal pigment epithelium, or brain. Animals show a diluted coat colour phenotype due to reduced melanin content in hair. Primary melanocytes from knockout animals are viable in culture and show a normal distribution of tyrosinase and tyrosinase-related protein 1
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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different sensitivity to inhibition by haematin
drug development
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the tautomerase activity of MIF is a target for inhibitor development, overview
medicine
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use of enzyme as an early differentiation marker for melanoblasts and retinal pigment epithelium
medicine
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different sensitivity to inhibition by haematin
medicine
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levels of enzyme correlate with relative levels of radioresistance and resistance to UV(B) treatment
medicine
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DCT is processed as a melanoma antigen and is a potential target for immunotherapy
medicine
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different sensitivity to inhibition by haematin