2.4.2.4: thymidine phosphorylase

This is an abbreviated version!
For detailed information about thymidine phosphorylase, go to the full flat file.

Reaction

Synonyms

angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase, animal growth regulators, blood platelet-derived endothelial cell growth factors, blood platelet-derived endothelial cell growth factor, deoA, deoxythymidine phosphorylase, dthdpase, EC 2.4.2.23, gliostatin, gliostatins, GLS, HTP, More, PD-ECGF, PD-ECGF/TP, PD-ECGF/TP platelet-derived endothelial cell growth factor, PDECGF, phosphorylase, thymidine, platelet derived endothelial cell growth factor, platelet derived endothelial cell grwoth factor, platelet derived-endothelial cell growth factor, platelet-derived endothelial cell growth factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase, platelet-derived endotherial cell growth factor, ppnP, pynpase, pyrimidine deoxynucleoside phosphorylase, pyrimidine nucleoside phosphorylase, pyrimidine phosphorylase, pyrimidine/purine nucleoside phosphorylase, TDRPASE, ThdPase, thymidine phosphorylase, thymidine Pi deoxyribosyltransferase, thymidine-orthophosphate deoxyribosyltransferase, thymidine:orthophosphate deoxy-D-ribosyltransferase, Tpase, TYMP

ECTree

     2 Transferases

         2.4 Glycosyltransferases

             2.4.2 Pentosyltransferases

                2.4.2.4 thymidine phosphorylase

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Results	in table
31	Activating Compound
12092	AA Sequence
43	Application
1	CAS Registry Number
24	Cloned(Commentary)
14	Crystallization (Commentary)
6222	Disease/ Diagnostics
7	Expression
40	General Information
8	General Stability
366	IC50 Value
694	Inhibitors
3	kcat/KM [mM/s]
161	Ki Value [mM]
81	KM Value [mM]
17	Localization
34	Molecular Weight [Da]
82	Natural Substrates/ Products (Substrates)
366	Organism
6	Pathway
41	PDB ID
39	pH Optimum
4	pH Range
1	pH Stability
1	pI Value
2	Posttranslational Modification
27	Protein Variants
36	Purification (Commentary)
12	Reaction
2	Reaction Type
186	Reference
260	Source Tissue
40	Specific Activity [micromol/min/mg]
7	Storage Stability
289	Substrates and Products (Substrate)
30	Subunits
111	Synonyms
1	Systematic Name
18	Temperature Optimum [°C]
6	Temperature Stability [°C]
34	Turnover Number [1/s]

Engineering

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Engineering on EC 2.4.2.4 - thymidine phosphorylase

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PROTEIN VARIANTS

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

D203A

2 entries

H116F

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

H116K

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

I214A

Homo sapiens

P19971

site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme

702064

K115A

Homo sapiens

P19971

site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme

702064

K115E

4 entries

L148R

3 entries

R202E

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

R202S

3 entries

S217G

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

Y199A

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

Y199F

Homo sapiens

P19971

site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme

702064

Y199L

Homo sapiens

P19971

site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme

702064

additional information

6 entries

D203A

Homo sapiens

P19971

site-directed mutagenesis, the mutant enzyme shows 50fold reduced catalytic efficiency compared to the wild-type enzyme, the mutant also shows pronounced resistance to the inhibitory effect of 5'-O-tritylinosine, and it keeps full sensitivity to the competitive inhibitors 6-aminothymine and 6-amino-5-bromouracil

702162

D203A

Homo sapiens

-

site-directed mutagenesis, the mutant shows 60% reduced phosphorolytic activity compared to the wild-type enzyme. The mutant is inhibited by 6-aminothymine 6-amino-5-bromouracil, like the wild-type enzyme, but not by 5'-O-tritylinosine, in contrast to the wild-type enzyme

705495

K115E

Homo sapiens

-

inactive mutant

705495

K115E

Homo sapiens

-

no enzyme activity after transfection in COS-7 cells

638464

K115E

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

K115E

Homo sapiens

-

loss of enzymic activity. Expression of mutant in rat vascular smooth muscle cell does not have significant effect on cell proliferation

721729

L148R

Homo sapiens

-

no enzyme activity after transfection in COS-7 cells

638464

L148R

Homo sapiens

-

mutant devoid of enzymatic activity

685026

L148R

Homo sapiens

-

loss of enzymic activity. Expression of mutant in rat vascular smooth muscle cell does not have significant effect on cell proliferation

721729

R202S

Homo sapiens

-

no enzyme activity after transfection in COS-7 cells

638464

R202S

Homo sapiens

P19971

site-directed mutagenesis, inactive mutant

702064

R202S

Homo sapiens

-

loss of enzymic activity. Expression of mutant in rat vascular smooth muscle cell does not have significant effect on cell proliferation

721729

additional information

Homo sapiens

-

downregulation of the enzyme by siRNA. Double knockout mutant cells, TP-/-UP-/-, lacking thymidine phosphorylase and uridine phosphorylase activities, show 100fold higher thymidine levels than the wild-type

705495

additional information

Homo sapiens

-

gene silencing results in a significant increase in basal and oxidative stress-induced apoptosis, the effect is abrogated by supplementation with 2-deoxy-D-ribose-1-phosphate

703240

additional information

Homo sapiens

P19971

transfection of TP into KB cells renders them highly resistant to apoptosis caused by hypoxia

759143

additional information

Mus musculus

-

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

705495

additional information

Mus musculus

-

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

703961

additional information

Mus musculus C57Bl6/J

-

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

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