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Information on EC 2.4.2.4 - thymidine phosphorylase and Organism(s) Mus musculus and UniProt Accession Q99N42
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2.4.2.4 thymidine phosphorylaseIUBMB Comments
The enzyme in some tissues also catalyses deoxyribosyltransferase reactions of the type catalysed by EC 2.4.2.6, nucleoside deoxyribosyltransferase.
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Word Map
- 2.4.2.4
- 5-fluorouracil
-
angiogenic
- colorectal
- thymidylate
- dihydropyrimidine
- capecitabine
-
microvessels
- metastasis
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clinicopathological
- uridine
-
mngie
-
neurogastrointestinal
- tumour
- 5'-deoxy-5-fluorouridine
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fluoropyrimidine
- thymine
-
5\'-dfur
-
resect
-
encephalomyopathy
-
prodrugs
- lymph
-
intratumoral
- deoxyuridine
- uracil
- orotate
-
phosphorolysis
-
dysmotility
- tpi
-
cachexia
- phosphorylases
- leukoencephalopathy
- ophthalmoplegia
- medicine
-
5-fu-based
-
ptosis
-
taxanes
- pseudo-obstruction
-
tegafur
- deoxyribose
- 5-fluoro-2'-deoxyuridine
-
viii-related
-
hand-foot
- fdump
- ophthalmoparesis
- trifluorothymidine
- analysis
- 5-fluorouridine
-
anti-cd34
-
5-fluorouracil-based
-
tp-induced
- 2'-deoxyuridine
- synthesis
-
fluoropyrimidine-based
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
thymidine phosphorylase, pd-ecgf, dthdpase, platelet-derived endothelial cell growth factor, pynpase, pd-ecgf/tp, pyrimidine nucleoside phosphorylase, pdecgf, platelet-derived endothelial cell growth factor/thymidine phosphorylase, gliostatin, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
animal growth regulators, blood platelet-derived endothelial cell growth factors
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-
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blood platelet-derived endothelial cell growth factor
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-
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deoxythymidine phosphorylase
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dthdpase
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-
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gliostatin
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-
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gliostatins
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PD-ECGF
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PD-ECGF/TP platelet-derived endothelial cell growth factor
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phosphorylase, thymidine
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pyrimidine deoxynucleoside phosphorylase
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pyrimidine phosphorylase
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TDRPASE
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-
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thymidine-orthophosphate deoxyribosyltransferase
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-
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thymidine:orthophosphate deoxy-D-ribosyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
sequential random bi-bi mechanism
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
rapid equilibrium random bi-bi mechanism with an enzyme-phosphate-thymine dead-end complex
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pentosyl group transfer
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-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
thymidine:phosphate deoxy-alpha-D-ribosyltransferase
The enzyme in some tissues also catalyses deoxyribosyltransferase reactions of the type catalysed by EC 2.4.2.6, nucleoside deoxyribosyltransferase.
CAS REGISTRY NUMBER
COMMENTARY
9030-23-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
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-
-
r
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
thymidine + phosphate
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-
-
r
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
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-
-
-
r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
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-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
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-
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r
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-deoxy-alpha-D-ribose 1-phosphate
dRib-1-P is a competitive product inhibitor of the forward reaction, in the reverse reaction, dRib-1-P enhances the binding of thymine
thymine
thymine is a product activator, but becomes a competitive inhibitor at concentrations eight times higher than its Km
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
paclitaxel
the expression of thymidine phosphorylase mRNA is up-regulated by the administration of paclitaxel (20 mg/kg)
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
no activities in other tissues than liver from TP-/-UP-/- mice
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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collagen-, collagen-related peptide-, adenosine diphosphate-and/or thrombin-induced platelet aggregation are significantly attenuated in enzyme deficient platelets. Tymp deficiency also significantly decreases agonist-induced P-select in expression
physiological function
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the enzyme participates in platelet signaling and promotes thrombosis by platelet activation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TYPH_MOUSE
471
0
49336
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
generation of double knockout mutant mice, TP-/-UP-/-, lacking thymidine phosphorylase and uridine phosphorylase activities, the mutant plasma thymidine levels are 5fold higher than in wild-type, but no alterations in mtDNA or pathological changes in the muscles occur in the knockout mice. Only in the brain, mitochondrial DNA depletion, respiratory chain defects and histological alterations, brain-specific phenotype, overview
additional information
-
generation of thymidine phosphorylase, TP, and uridine phosphorylase, UP, EC 2.4.2.3, double knockout mice, TP-/-UP-/- by insertion mutagenesis, which show severe TP deficiency, increased thymidine and deoxyuridine levels in tissues and elevated mitochondrial deoxythymidine triphosphate. As consequences of the nucleotide pool imbalances, brains of mutant mice developed partial depletion of mtDNA, deficiencies of respiratory chain complexes and encephalopathy, accounting for the pathogenesis of mitochondrial neurogastrointestinal encephalopathy, overview. Mitochondria respiratory chain deficiency in the brain of TP-/-UP-/- mice, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Iltzsch, M.H.; El Kouni, M.H.; Cha, S.
Kinetic studies of thymidine phosphorylase from mouse liver
Biochemistry
24
6799-6807
1985
Mus musculus
el Kouni, M.H.; el Kouni, M.M.; Naguib, F.N.
Differences in activities and substrate specificity of human and murine pyrimidine nucleoside phosphorylases: implications for chemotherapy with 5-fluoropyrimidines
Cancer Res.
53
3687-3693
1993
Homo sapiens, Mus musculus
Sakurai, Y.; Yoshida, I.; Kamoshida, S.; Inaba, K.; Isogaki, J.; Komori, Y.; Uyama, I.; Tsutsumi, Y.
Changes of gene expression of thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase after the administration of 5-deoxy-5-fluorouridine, paclitaxel and its combination in human gastric cancer xenografts
Anticancer Res.
28
1593-1602
2008
Homo sapiens, Mus musculus (Q99N42), Mus musculus
Lopez, L.C.; Akman, H.O.; Garcia-Cazorla, A.; Dorado, B.; Marti, R.; Nishino, I.; Tadesse, S.; Pizzorno, G.; Shungu, D.; Bonilla, E.; Tanji, K.; Hirano, M.
Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice
Hum. Mol. Genet.
18
714-722
2009
Mus musculus, Mus musculus C57Bl6/J
Bronckaers, A.; Gago, F.; Balzarini, J.; Liekens, S.
The dual role of thymidine phosphorylase in cancer development and chemotherapy
Med. Res. Rev.
29
903-953
2009
Geobacillus stearothermophilus, Escherichia coli, Homo sapiens, Mus musculus, Rattus norvegicus, Salmonella enterica subsp. enterica serovar Typhimurium
Li, W.; Gigante, A.; Perez-Perez, M.J.; Yue, H.; Hirano, M.; McIntyre, T.M.; Silverstein, R.L.
Thymidine phosphorylase participates in platelet signaling and promotes thrombosis
Circ. Res.
115
997-1006
2014
Mus musculus
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