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Information on EC 4.1.1.84 - D-dopachrome decarboxylase
for references in articles please use BRENDA:EC4.1.1.84
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IUBMB Comments
This enzyme is specific for D-dopachrome as substrate and belongs to the MIF (macrophage migration inhibitory factor) family of proteins. L-Dopachrome, L- or D-α-methyldopachrome and dopaminochrome do not act as substrates (see also EC 5.3.3.12, L-dopachrome isomerase)
The enzyme appears in viruses and cellular organisms
showSynonyms
d-dopachrome decarboxylase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D-dopachrome tautomerase
D-DT
D-tautomerase
distinct from EC 5.3.3.12, dopachrome isomerase, and from EC 5.3.2.1, phenylpyruvate tautomerase or MIF
DDT
phenylpyruvate tautomerase
-
identical with phenylpyruvate tautomerase, EC 5.3.2.1
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
D-dopachrome = 5,6-dihydroxyindole + CO2
-
-
-
-
D-dopachrome = 5,6-dihydroxyindole + CO2
animal experiments with CCl4 injections, results suggest that the increase in DDT is a response to liver damage, accelerates melanin biosynthesis and protects the liver from oxidative stress induced by CCl4
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SYSTEMATIC NAME
IUBMB Comments
D-dopachrome carboxy-lyase (5,6-dihydroxyindole-forming)
This enzyme is specific for D-dopachrome as substrate and belongs to the MIF (macrophage migration inhibitory factor) family of proteins. L-Dopachrome, L- or D-alpha-methyldopachrome and dopaminochrome do not act as substrates (see also EC 5.3.3.12, L-dopachrome isomerase)
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CAS REGISTRY NUMBER
COMMENTARY
184111-06-6
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-chlorophenylpyruvate
4-chlorophenylpyruvate
Substrates: -
Products: -
Products: -
?
4-methoxyphenylpyruvate
4-methoxyphenylpyruvate
Substrates: -
Products: -
Products: -
?
indole-3-pyruvate
indole-3-pyruvate
-
Substrates: enol form
Products: keto form
Products: keto form
?
additional information
?
-
Substrates: no substrates are: L-dopachrome, dopaminochrome, L-alpha-methyldopachrome, D-alpha-methyldopachrome
Products: -
Products: -
?
4-hydroxyphenylpyruvate
4-hydroxyphenylpyruvate
Substrates: -
Products: -
Products: -
?
4-hydroxyphenylpyruvate
4-hydroxyphenylpyruvate
-
Substrates: enol form
Products: keto form
Products: keto form
?
D-dopachrome
5,6-dihydroxyindole + CO2
Substrates: -
Products: -
Products: -
?
Phenylpyruvate
Phenylpyruvate
-
Substrates: enol form
Products: keto form
Products: keto form
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-2-amino-4-methyl-N-(1-(naphthalen-1-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)thiophene-3-carboxamide
-
(R)-5-methyl-3-(1-(naphthalen-1-yl)ethyl)-6-(3-(trifluoromethyl)-phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
suppresses the proliferation of non-small cell lung cancer cells in two-dimensional and three-dimensional cell cultures, low micromolar level potency for inhibition of both MIF2 tautomerase activity and cancer cell proliferation
(S)-5-methyl-3-(1-(naphthalen-1-yl)ethyl)-6-(3-(trifluoromethyl)-phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
-
2-amino-4-methyl-N-[(naphthalen-1-yl)methyl]-5-(3-(trifluoromethyl)phenyl)thiophene-3-carboxamide
-
3-benzyl-5-methyl-6-(3-(trifluoromethyl)phenyl)thieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
-
3-benzyl-6-(2,4-dichlorophenyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
-
3-benzyl-6-(3,4-dichlorophenyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
-
4-(3-carboxyphenyl)-2,5-pyridinedicarboxylic acid
specifically inhibits DDT-induced PGE2 production in astrocytes
-
4-iodo-6-phenylpyrimidine
inhibition of DDT is efficient in attenuating DDT-induced astrocyte production of PGE2 following spinal cord injury
5-methyl-3-(naphthalen-1-ylmethyl)-6-(3-(trifluoromethyl)-phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
-
6-(4-chlorophenyl)-2-(3-methoxybenzyl)-5-methylthieno[2,3-d]-pyrimidin-4(1H)-one
-
6-(4-chlorophenyl)-5-methyl-3-(4-(trifluoromethyl)benzyl)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
-
6-(benzo[d][1,3]dioxol-5-yl)-3-benzyl-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0042
(R)-2-amino-4-methyl-N-(1-(naphthalen-1-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)thiophene-3-carboxamide
Homo sapiens
pH 6.0, 22°C
0.001
(R)-5-methyl-3-(1-(naphthalen-1-yl)ethyl)-6-(3-(trifluoromethyl)-phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
0.0025
(S)-5-methyl-3-(1-(naphthalen-1-yl)ethyl)-6-(3-(trifluoromethyl)-phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
0.0026
2-amino-4-methyl-N-[(naphthalen-1-yl)methyl]-5-(3-(trifluoromethyl)phenyl)thiophene-3-carboxamide
Homo sapiens
pH 6.0, 22°C
0.0017
3-benzyl-5-methyl-6-(3-(trifluoromethyl)phenyl)thieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
0.0035
3-benzyl-6-(2,4-dichlorophenyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
0.0019
3-benzyl-6-(3,4-dichlorophenyl)-5-methylthieno[2,3-d]-pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
0.00081
5-methyl-3-(naphthalen-1-ylmethyl)-6-(3-(trifluoromethyl)-phenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
0.0043
6-(4-chlorophenyl)-2-(3-methoxybenzyl)-5-methylthieno[2,3-d]-pyrimidin-4(1H)-one
Homo sapiens
pH 6.0, 22°C
0.0048
6-(4-chlorophenyl)-5-methyl-3-(4-(trifluoromethyl)benzyl)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
pH 6.0, 22°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
transcripts are detected in all tested tissues
brenda
DDT is inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion
brenda
DDT is inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion
brenda
DDT is inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
treatment with a DDT-specific antibody induces themigration of monocytes/macrophages and lymphocytes both in vitro and in vivo, without significant influence on the migration of neutrophils. Recombinant DDT exhibits chemotactic activity for lipopolysaccharide-stimulated M1-type monocytes/macrophages in vitro
physiological function
DDT promotes proliferation of and prevents staurosporine-induced apoptosis in A-549 lung epithelial cells. DDT also stimulates growth of primary alveolar epithelial cells. DDT treatment results in significantly more and larger murine and human alveolar organoids compared to untreated controls. The anti-apoptotic effect of DDT and DDT-induced organoid growth are inhibited in the presence of an ACKR3-blocking nanobody. DDT complexes with ACKR3. DDT can activate the PI3K-Akt pathway which is enhanced in ACKR3-overexpressing cells
physiological function
chronic UVB exposure accelerates tumor development in DDT overexpressing mice, with a higher incidence of tumors observed in DDT overexpressing mice than in wild-type mice. In DDT overexpressing irradiated mouse keratinocytes, the p53, PUMA, and Bax expression is lower than that in wild-type
physiological function
recombinant DDT is able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, the intracellular activation of mitogen-activated protein kinases is involved in the regulation of DDT action. Inhibition of DDT promotes the recovery of motor function following spinal cord injury
physiological function
DDT protein levels are significantly elevated within neurons and astrocytes following spinal cord injury. Recombinant DDT is efficient in inducing the production of inflammatory cytokines from astrocytes through interaction with CD74 receptor. Activation of mitogen-activated protein kinases and NF-kappaB is essential for the transduction of DDT signaling
Show AA Sequence and Transmembrane Helices (857 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
trimer
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
atractylenolide 1 stimulates autophagic flux to downregulate expression of D-dopachrome tautomerase. Deacetylation of p53 is pivotal for the induction of autophagic flux
upon infection with Vibrio harveyi, DDT transcripts are significantly downregulated in liver, spleen, and head kidney
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
strong correlation and covariation of enzyme activity with macrophage migration inhibitory factor, MIF, upon UVB-induction
medicine
-
DDT may be candidates for key enzymes to protect the liver from oxidative stress induced by various causes
medicine
atractylenolide 1 reduces intestinal adenoma formation through activating autophagy machinery to downregulate D-dopachrome tautomerase
medicine
atractylenolide 1 reduces intestinal adenoma formation through activating autophagy machinery to downregulate D-dopachrome tautomerase. Atractylenolide 1 stimulates autophagic flux through downregulating acetylation of p53
medicine
DDT promotes A-549 epithelial cell proliferation and protects them from apoptosis. DDT mediates its anti-apoptotic effects through ACKR3 in A-549 epithelial cells
medicine
DDT is associated with UVB-induced skin tumorigenesis. DDT overexpression exerts p53-antagonizing effects and inhibits the apoptosis signaling pathway
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Odh, G.; Hindemith, A.; Rosengren, A-M.; Rosengren, E.; Rorsman, H.
Isolation of a new tautomerase monitored by the conversion of D-dopachrome to 5,6-dihydroxyindole
Biochem. Biophys. Res. Commun.
197
619-624
1993
Rattus norvegicus (P80254)
brenda
Nishihira, J.; Fujinaga, M.; Kuriyama, T.; Suzuki, M.; Sugimoto, H.; Nakagawa, A.; Tanaka, I.; Sakai, M.
Molecular cloning of human D-dopachrome tautomerase cDNA: N-terminal proline is essential for enzyme activation
Biochem. Biophys. Res. Commun.
243
538-544
1998
Homo sapiens (P30046)
brenda
Yoshida, H.; Nishihira, J.; Suzuki, M.; Hikichi, K.
NMR characterization of physicochemical properties of rat D-dopachrome tautomerase
Biochem. Mol. Biol. Int.
42
891-899
1997
Rattus norvegicus (P80254)
brenda
Sugimoto, H.; Taniguchi, M.; Nakagawa, A.; Tanaka, I.; Suzuki, M.; Nishihira, J.
Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 A resolution
Biochemistry
38
3268-3279
1999
Homo sapiens (P30046)
brenda
Kuriyama T.;Fujinaga M.;Koda T.;Nishihira J.
Cloning of the mouse gene for D-dopachrome tautomerase.
Biochim. Biophys. Acta
1388
506-512
1998
Mus musculus (O35215)
brenda
Bjoerk, P.; Aman, P.; Hindemith, A.; Odh, G.; Jacobsson, L.; Rosengren, E.; Rorsman, H.
A new enzyme activity in human blood cells and isolation of the responsible protein (D-dopachrome tautomerase) from erythrocytes
Eur. J. Haematol.
57
254-256
1996
Homo sapiens, Bos taurus
brenda
Sonesson, B.; Rosengren, E.; Hansson, A.S.; Hansson, C.
UVB-induced inflammation gives increased d-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor
Exp. Dermatol.
12
278-282
2003
Homo sapiens (P30046)
brenda
Sugimoto, H.; Taniguchi, M.; Nakagawa, A.; Tanaka, I.; Suzuki, M.; Nishihira, J.
Crystallization and preliminary x-ray analysis of human D-dopachrome tautomerase
J. Struct. Biol.
120
105-108
1997
Homo sapiens (P30046)
brenda
Rosengren, E.; Thelin, S.; Aman, P.; Hansson, C.; Jacobsson, L.; Rorsman, H.
The protein catalysing the conversion of D-dopachrome to 5,6-dihydroxyindole is a phenylpyruvate tautomerase (EC 5.3.2.1)
Melanoma Res.
7
517-518
1997
Rattus norvegicus
brenda
Coleman, A.M.; Rendon, B.E.; Zhao, M.; Qian, M.W.; Bucala, R.; Xin, D.; Mitchell, R.A.
Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase
J. Immunol.
181
2330-2337
2008
Homo sapiens (P30046), Mus musculus (O35215)
brenda
Hiyoshi, M.; Konishi, H.; Uemura, H.; Matsuzaki, H.; Tsukamoto, H.; Sugimoto, R.; Takeda, H.; Dakeshita, S.; Kitayama, A.; Takami, H.; Sawachika, F.; Kido, H.; Arisawa, K.
D-Dopachrome tautomerase is a candidate for key proteins to protect the rat liver damaged by carbon tetrachloride
Toxicology
255
6-14
2009
Rattus norvegicus
brenda
Garai, J.; Lorand, T.
Macrophage migration inhibitory factor (MIF) tautomerase inhibitors as potential novel anti-inflammatory agents: current developments
Curr. Med. Chem.
16
1091-1114
2009
Homo sapiens
brenda
Li, H.; He, B.; Zhang, X.; Hao, H.; Yang, T.; Sun, C.; Song, H.; Wang, Y.; Zhou, Y.; Zhu, Z.; Hu, Y.; Wang, Y.
D-dopachrome tautomerase drives astroglial inflammation via NF-kappaB signaling following spinal cord injury
Cell Biosci.
12
128
2022
Rattus norvegicus (P80254)
brenda
Song, S.; Liu, B.; Habibie, H.; van den Bor, J.; Smit, M.J.; Gosens, R.; Wu, X.; Brandsma, C.A.; Cool, R.H.; Haisma, H.J.; Poelarends, G.J.; Melgert, B.N.
D-dopachrome tautomerase contributes to lung epithelial repair via atypical chemokine receptor 3-dependent Akt signaling
EBioMedicine
68
103412
2021
Homo sapiens (P30046)
brenda
Yoshihisa, Y.; Rehman, M.U.; Andoh, T.; Tabuchi, Y.; Makino, T.; Shimizu, T.
Overexpression of D-dopachrome tautomerase increases ultraviolet B irradiation-induced skin tumorigenesis in mice
FASEB J.
35
e21671
2021
Mus musculus (O35215)
brenda
Li, L.; Jing, L.; Wang, J.; Xu, W.; Gong, X.; Zhao, Y.; Ma, Y.; Yao, X.; Sun, X.
Autophagic flux is essential for the downregulation of D-dopachrome tautomerase by atractylenolide I to ameliorate intestinal adenoma formation
J. Cell Commun. Signal.
12
689-698
2018
Homo sapiens (P30046), Mus musculus (O35215)
brenda
Xiao, Z.; Osipyan, A.; Song, S.; Chen, D.; Schut, R.A.; van Merkerk, R.; van der Wouden, P.E.; Cool, R.H.; Quax, W.J.; Melgert, B.N.; Poelarends, G.J.; Dekker, F.J.
Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione derivative inhibits D-dopachrome tautomerase activity and suppresses the proliferation of non-small cell lung cancer cells
J. Med. Chem.
65
2059-2077
2022
Homo sapiens (P30046)
brenda
Ji, H.; Zhang, Y.; Chen, C.; Li, H.; He, B.; Yang, T.; Sun, C.; Hao, H.; Zhang, X.; Wang, Y.; Zhou, Y.; Zhu, Z.; Hu, Y.; Li, A.; Guo, A.; Wang, Y.
D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury
J. Neuroinflammation
18
130
2021
Rattus norvegicus (P80254)
brenda
Xu, F.; Li, M.Y.; Chen, J.
D-dopachrome tautomerase from Japanese sea bass ( Lateolabrax japonicus) is a chemokine-like cytokine and functional homolog of macrophage migration inhibitory factor
Zool. Res.
41
39-50
2020
Lateolabrax japonicus
brenda
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