Information on EC 2.4.2.3 - uridine phosphorylase

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The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota

EC NUMBER
COMMENTARY
2.4.2.3
-
RECOMMENDED NAME
GeneOntology No.
uridine phosphorylase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
sequential mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
sequential mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
sequential mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
rapid-equilibrium random mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
ordered bi-bi mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
ordered bi-bi mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
random mechanism
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
phosphate binds before uridine and ribose 1-phosphate is released after uracil
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
sequential rather than ping-pong mechanism, addition of substrate is random
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
ordered bi-bi mechanism, phosphate binds before uridine and alpha-D-ribose 1-phosphate is released after uracil
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
binding isotope effects indicate ground-state stabilization in the Michaelis complex, such as bonding environment, ribosyl pucker, and natural bond orbital charges
-
uridine + phosphate = uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
steady-state random kinetic mechanism. Reaction follows an ANDN/SN2 mechanism where chemistry contributes significantly to the overall rate-limiting step of the reaction. No kinetically significant proton transfer step is involved at the transition state. Proton transfer to neutralize the leaving group is not part of transition state formation, consistent with an enzyme-stabilized anionic uracil as the leaving group. Kinetic analysis as a function of pH indicates one protonated group essential for catalysis and for substrate binding
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pentosyl group transfer
-
-
-
-
pentosyl group transfer
-
-
PATHWAY
KEGG Link
MetaCyc Link
Drug metabolism - other enzymes
-
Metabolic pathways
-
pyrimidine deoxyribonucleosides degradation
-
Pyrimidine metabolism
-
pyrimidine metabolism
BRENDA
BRENDA
BRENDA
pyrimidine ribonucleosides degradation
-
SYSTEMATIC NAME
IUBMB Comments
uridine:phosphate alpha-D-ribosyltransferase
The enzyme participates the the pathways of pyrimidine ribonucleosides degradation and salvage. The mammalian enzyme also accepts 2'-deoxyuridine.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
apUP
Q9YA34
-
apUP
Aeropyrum pernix DSM 11879
Q9YA34
-
-
phosphorylase, uridine
-
-
-
-
pyrimidine nucleoside phosphorylase
-
-
pyrimidine phosphorylase
-
-
-
-
udp
Q9K4U1
gene name
UDRPase
-
-
-
-
UP type 1
Q16831
-
UP1
Q16831
-
UPase
-
-
-
-
UPase
-
-
UPase
-
-
UPase
-
-
UPase-2
Q95045
-
UPase-2
-
-
UPH
-
-
-
-
UPP1
Q16831
-
UPP2
O95045
-
UrdPase
-
-
-
-
uridine phosphorylase
-
-
uridine phosphorylase
Q57VZ2
-
uridine phosphorylase 1
Q16831
-
uridine phosphorylase-2
Q95045
-
uridine phosphorylase-2
-
-
uridine:orthophosphate alpha-D-ribosyltransferase
-
-
-
-
L-UrdPase
-
-
additional information
Q57VZ2
the enzyme belongs to the NP1 subfamily of the nucleoside phosphorylase, NP, superfamily of enzymes
CAS REGISTRY NUMBER
COMMENTARY
9030-22-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Aeropyrum pernix DSM 11879
-
SwissProt
Manually annotated by BRENDA team
cattle
-
-
Manually annotated by BRENDA team
Enterobacter aerogenes AJ 11125
AJ 11125
-
-
Manually annotated by BRENDA team
B-96, ATCC 13473, two types of enzyme, I and II
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
isozyme UPP1
UniProt
Manually annotated by BRENDA team
UP1; type 1 enzyme
UniProt
Manually annotated by BRENDA team
C3H/He female mice
-
-
Manually annotated by BRENDA team
Fischer 344 male rats
-
-
Manually annotated by BRENDA team
wild type and uridine phosphorylase deficient strain
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-, Q16831
uridine phosphorylase is a key enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate
metabolism
Q16831
uridine phosphorylase is a ubiquitous enzyme involved in pyrimidine salvage and maintenance of uridine homeostasis
physiological function
-
the enzyme contributes to the antineoplastic activity of 5'-deoxy-5-fluorouridine. The peroxisome proliferator-activated receptor gamma coactivator-1alpha enhances antiproliferative activity of 5-deoxy-5-fluorouridine in cancer cells through induction of uridine phosphorylase, overview
physiological function
Q16831
uridine phosphorylase is a ubiquitous enzyme involved in pyrimidine salvage and maintenance of uridine homeostasis. UPP1 plays a role in the activation of pyrimidine nucleoside analogues used in chemotherapy, such as 5-fluorouracil and its prodrug, capecitabine
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
-
-
-
r
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
unlike cytosolic enzyme, enzyme from plasma membranes shows little or no deoxyuridine-cleaving activity
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
12% of the activity with uridine
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
18% of the activity with uridine
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
activities of uridine, deoxyuridine and thymidine phosphorylase from Giardia lamblia remain associated throughout purification suggesting that a single enzyme is responsible for the 3 activities
-
-
?
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
catalyzed by a different protein or by a different active center of the same enzyme
-
r
2'-deoxyuridine + phosphate
uracil + deoxyribose 1-phosphate
show the reaction diagram
-
6% of the activity with uridine
-
?
5'-deoxy-5-fluorouridine + alpha-D-ribose 1-phosphate
5'-deoxy-5-fluorouridine + phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
show the reaction diagram
-
25% of the activity with uridine
-
-
?
5-bromo-2'-deoxyuridine + phosphate
5-bromouracil + 2-deoxribose 1-phosphate
show the reaction diagram
-
27% of the activity with uridine
-
-
?
5-bromo-2'-deoxyuridine + phosphate
5-bromouracil + 2-deoxribose 1-phosphate
show the reaction diagram
-
75% of the activity with uridine
-
-
?
5-bromouracil + deoxyribose 1-phosphate
5-bromodeoxyuridine + phosphate
show the reaction diagram
-
-
-
-
-
5-bromouracil + deoxyribose 1-phosphate
5-bromodeoxyuridine + phosphate
show the reaction diagram
-
-
-
-
?
5-bromouridine + phosphate
5-bromouracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-bromouridine + phosphate
5-bromouracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
69% of the activity with uridine
-
-
?
5-bromouridine + phosphate
5-bromouracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
40% of the activity with uridine
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
show the reaction diagram
-
15% of the activity with uridine
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
show the reaction diagram
-
14% of the activity with uridine
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
Q95045
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxy-D-ribose-1-phosphate
show the reaction diagram
-
-
also accepts 2'-deoxypyrimidine nucleosides in higher organisms
-
r
5-fluorouracil + alpha-D-ribose 1-phosphate
5-fluorouridine + phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouracil + alpha-D-ribose-1-phosphate
5-fluorouridine + phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
show the reaction diagram
Q95045
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
show the reaction diagram
-
15% of the activity with uridine
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose-1-phosphate
show the reaction diagram
-
85% of the activity with uridine
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
27% of the activity with uridine
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
92% compared to the activity with uridine
-
-
?
5-methyluridine + phosphate
5-methyluracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Aeropyrum pernix DSM 11879
Q9YA34
92% compared to the activity with uridine
-
-
?
5-methyluridine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
19% of the activity with uridine
-
-
?
arabinofuranosyl-5-ethyluracil + phosphate
5-ethyluracil + arabinose-1-phosphate
show the reaction diagram
-
weak substrate
-
-
?
azathymine + deoxyribose 1-phosphate
azadeoxythymidine + phosphate
show the reaction diagram
-
-
-
-
ir
azauracil + deoxyribose 1-phosphate
azadeoxyuridine + phosphate
show the reaction diagram
-
-
-
-
?
azauracil + ribose 1-phosphate
azauridine + phosphate
show the reaction diagram
-
-
-
-
ir
cytidine + phosphate
cytosine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
deoxyuridine + phosphate
uracil + deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
deoxyuridine + phosphate
uracil + deoxy-D-ribose 1-phosphate
show the reaction diagram
-
66% compared to the activity with uridine
-
-
?
deoxyuridine + phosphate
uracil + deoxy-D-ribose 1-phosphate
show the reaction diagram
Aeropyrum pernix DSM 11879
Q9YA34
66% compared to the activity with uridine
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
Q95045
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
Q57VZ2, -
14% of the activity with uridine
-
-
r
fluorouridine + phosphate
fluorouracil + alpha-D-ribose-1-phosphate
show the reaction diagram
-
-
-
-
?
guanosine + phosphate
guanine + alpha-D-ribose 1-phosphate
show the reaction diagram
Q57VZ2, -
10% of the activity with uridine
-
-
r
pyrimidine nucleoside + phosphate
pyrimidine base + alpha-D-ribose 1-phosphate
show the reaction diagram
-
most pyrimidine nucleosides except for 4-amino-substituted species like deoxycytidine
or alpha-D-deoxyribose 1-phosphate
-
r
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
Q95045
-
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
the activities of uridine, deoxyuridine and thymidine phosphorylases from Giardia lamblia remain associated throughout purification, suggesting that a single enzyme is responsible for the 3 activities
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
2% of the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
21% of the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
22% of the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
to a lesser extent compared to uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
to a lesser extent compared to uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
-
60% compared to the activity with uridine
-
-
?
thymidine + phosphate
thymine + alpha-D-ribose 1-phosphate
show the reaction diagram
Aeropyrum pernix DSM 11879
Q9YA34
60% compared to the activity with uridine
-
-
?
thymine + deoxyribose 1-phosphate
deoxythymidine + phosphate
show the reaction diagram
-
-
-
-
?
thymine + ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
-
-
-
?
uracil + alpha-D-ribose 1-phosphate
uridine + phosphate
show the reaction diagram
-
-
-
-
?
uracil + alpha-D-ribose 1-phosphate
uridine + phosphate
show the reaction diagram
-
-, uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase
-
-
?
uracil arabinoside + phosphate
uracil + arabinose-1-phosphate
show the reaction diagram
-
-
-
-
?
uracil arabinoside + phosphate
uracil + arabinose-1-phosphate
show the reaction diagram
-
10% of the activity with uridine
-
-
?
uracil arabinoside + phosphate
uracil + arabinose-1-phosphate
show the reaction diagram
-
10% of the activity with uridine
-
-
?
uridine + arsenate
?
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q95045
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-, Q16831
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q16831
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q57VZ2, -
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q8I3X4
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
equilibrium position favouring nucleoside synthesis
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
liver enzyme is highly specific to uridine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
broader specificity than human enzyme
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
in conjunction with uridine kinase, the enzyme provides a route for the conversion of uracil to UMP via uridine
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
role in degradation of pyrimidine nucleosides as well as in the salvage pathway for nucleic acid synthesis
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
enzyme of pyrimidine salvage pathway
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
enzyme of pyrimidine salvage pathway
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
key enzyme in pyrimidine-salvage pathway
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q57VZ2, -
best substrate, active site structure, overview
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
cleavage of the N-glycosidic bond
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
the optimal substrate for the enzyme is uridine. It shows no activity for 5-fluorouridine, cytidine, or 2-deoxycytidine
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Aeropyrum pernix DSM 11879
Q9YA34
the optimal substrate for the enzyme is uridine. It shows no activity for 5-fluorouridine, cytidine, or 2-deoxycytidine
-
-
?
inosine + phosphate
hypoxanthine + alpha-D-ribose 1-phosphate
show the reaction diagram
Q8I3X4
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
no substrates: inosine, adenosine, guanosine, thymidine
-
-
-
additional information
?
-
-
no substrates are: thymidine, deoxyuridine, fluorodeoxyuridiune, 5'-deoxyfluorouridine
-
-
-
additional information
?
-
-
no substrate: cytidine
-
-
-
additional information
?
-
-
no substrate: cytidine
-
-
-
additional information
?
-
-
no substrate: cytidine
-
-
-
additional information
?
-
-
no substrate: cytidine
-
-
-
additional information
?
-
-
no substrate: 5-substituted-2,2'-anhydrouridine
-
-
-
additional information
?
-
-
no substrates: 3'-azido-2',3'-dideoxy-5-methyluridine, 3'-azido-2',3'-dideoxy-5-ethyluridine, 2',3'-dideoxy-5-ethyluridine, 3'-chloro-2',3'-dideoxy-5-ethyluridine, 3'-chloro-2',3'-dideoxy-5-methyluridine, 3'-bromo-2',3'-dideoxy-5-ethyluridine, 2'-deoxylyxofuranosyl-5-ethyluracil, 3'-O-acetyl-2,2'-anhydro-5-ethyluridine, 2,3'-anhydro-2'-deoxy-5-ethyluridine, 2,5'-anhydro-2'-deoxy-5-ethyluridine
-
-
-
additional information
?
-
-
no substrates: 2-deoxyuridine, adenosine
-
-
-
additional information
?
-
-
no substrates: cytosine, deoxycytidine, orotidine
-
-
-
additional information
?
-
-
the enzyme is regulated by multiple lipid-sensing nuclear receptors, gene expression is diurnally regulated
-
-
-
additional information
?
-
-
catalyzes the first step of uridine degradation to beta-alanine in liver
-
-
-
additional information
?
-
-
the enzyme also activates pyrimidine-containing drugs, including 5-fluorouracil, mechanism of the enzyme-drug interaction, overview
-
-
-
additional information
?
-
Q16831
UPP catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose-1-phosphate, structural mechanisms, overview
-
-
-
additional information
?
-
Q57VZ2, -
strict substrate specificty of the enzyme, overview. Deoxyadenosine, and deoxyguanosine are poor substrates, thymidine, cytidine, deoxycytidine, inosine, and adenosine are no substrates
-
-
-
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
pyrimidine nucleoside + phosphate
pyrimidine base + alpha-D-ribose 1-phosphate
show the reaction diagram
-
most pyrimidine nucleosides except for 4-amino-substituted species like deoxycytidine
or alpha-D-deoxyribose 1-phosphate
-
r
uracil + alpha-D-ribose 1-phosphate
uridine + phosphate
show the reaction diagram
-
uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q16831
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
Q57VZ2, -
-
-
-
r
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
in conjunction with uridine kinase, the enzyme provides a route for the conversion of uracil to UMP via uridine
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
role in degradation of pyrimidine nucleosides as well as in the salvage pathway for nucleic acid synthesis
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
enzyme of pyrimidine salvage pathway
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
enzyme of pyrimidine salvage pathway
-
-
-
uridine + phosphate
uracil + alpha-D-ribose 1-phosphate
show the reaction diagram
-
key enzyme in pyrimidine-salvage pathway
-
-
?
additional information
?
-
-
the enzyme is regulated by multiple lipid-sensing nuclear receptors, gene expression is diurnally regulated
-
-
-
additional information
?
-
-
catalyzes the first step of uridine degradation to beta-alanine in liver
-
-
-
additional information
?
-
-
the enzyme also activates pyrimidine-containing drugs, including 5-fluorouracil, mechanism of the enzyme-drug interaction, overview
-
-
-
additional information
?
-
Q16831
UPP catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose-1-phosphate, structural mechanisms, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
Q57VZ2, -
stabilizes the enzyme, which possesses an intermolecular metal-binding site, structure, overview
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-((2-pyrrolidine-1-yl)ethyl)uracil
Q8I3X4
inhibits both enzymic activity and growth of Plasmodium falciparum
1-(1',2'-dihydroxypropyl)-5,6-tetramethyleneuracil
-
only the R-enantiomer inhibits, but not the S-enantiomer
1-(1',3'-dihydroxy-2'-propoxy)methyl-5,6-tetramethyleneuracil
-
inhibits forward and reverse reaction
1-(1',3'-dihydroxy-2'-propoxy)methyl-5-benzyluracil
-
i.e. DHPBU, competitive
2',3'-Dideoxy-5-ethyluridine
-
-
2'-deoxyglycosylthymine
-
-
2'-Deoxylyxofuranosyl-5-ethyluracil
-
-
2,2'-Anhydro-5-ethyluridine
-
-
2,2'-Anhydro-5-ethyluridine
-
-
2,2'-Anhydro-5-ethyluridine
-
-
2,2'-Anhydro-5-ethyluridine
-
0.001 mM, competitive
2,2'-Anhydro-5-ethyluridine
-
competitive
2,3'-Anhydro-2'-deoxy-5-ethyluridine
-
-
2,3'-anhydro-5-ethyluridine
-
competitive
2,5'-Anhydro-2'-deoxy-5-ethyluridine
-
-
2-deoxyglycosylthymine
-
-
3'-Azido-2',3'-dideoxy-5-ethyluridine
-
-
3'-Azido-2',3'-dideoxy-5-methyluridine
-
-
3'-Bromo-2',3'-dideoxy-5-ethyluridine
-
-
3'-Chloro-2',3'-dideoxy-5-ethyluridine
-
-
3'-Chloro-2',3'-dideoxy-5-methyluridine
-
-
3'-O-Acetyl-2,2'-anhydro-5-ethyluridine
-
-
3-((2-pyrrolidine-1-yl)ethyl)uracil
Q8I3X4
inhibits both enzymic activity and growth of Plasmodium falciparum
3-O-methyl-alpha-D-glucopyranose
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
-
5-(3'-Benzyloxybenzyl)-1-[(1'-aminomethyl-2'-hydroxyethoxy)methyl]uracil
-
-
5-(Benzyloxybenzyloxybenzyl)acyluridine
-
-
-
5-(phenylthio)acyclouridine
-
-
5-(phenylthio)acyclouridine
-
specific inhibitor
5-Azauracil
-
reaction is inhibited in the direction of deoxyuridine synthesis more than in the direction of their cleavage at the same concentration of 5-azauracil
5-benzylacyclouridine
-
0.01 mM, 90% inhibition of normal tissues, 40-60% inhibition of carcinoma tissue
5-benzylacyclouridine
-
-
5-benzylacyclouridine
-
-
5-benzylacyclouridine
Q16831
an UPP1-specific inhibitor. Binding of the inhibitor to the UPP1 active site, structure, overview
5-bromoacyclouridine
-
-
5-fluoro-2'-deoxyuridine
-
-
5-fluoro-2'-deoxyuridine
-
-
5-fluoroacyclouridine
-
-
5-iodoacyclouridine
-
-
5-m-benzyloxybenzyl acyclouridine
-
-
5-m-benzyloxybenzyl barbituric acid acyclonucleoside
-
-
5-phenylselenenylacyclouridine
-
-
5-phenylthioacyclouridine
-
-
5-Substituted 2,2'-anhydrouridine
-
-
6-Methyluracil
-
-
Acyclonucleoside analogues
-
consisting of 5- and 5,6-substituted uracils and different acyclic chains
-
Acyclothymidine
-
competitive
acyclouridine
-
competitive
alpha-D-ribose 1-phosphate
-
-
alpha-D-ribose 1-phosphate
-, Q16831
product inhibition pattern, noncompetitive versus uridine, competitive versus phosphate, overview
alpha-D-ribose 1-phosphate
-
product inhibition, noncompetitive with respect to uridine and phosphate
Arabinofuranosyl-5-ethyluracil
-
-
Benzylacyclouridines
-
0.1 mM
-
Benzylacyclouridines
-
-
-
Benzylacyclouridines
-
-
-
Deoxyglucosylthymine
-
phosphorolysis of uridine and deoxyuridine, synthesis of uridine at concentrations of 0.10 mM, 0.018 mM and 0.14 mM, not: phosphorolysis of deoxyuridine or thymidine at 0.19 mM
deoxythymidine
-
-
guanidine hydrochloride
-
50% loss of activity at 1.04 M, only little residual activity between 2 and 6 M
iodoacetamide
-
-
iodoacetic acid
-
-
N-ethyl-5-phenylisoxazolium-3'-sulfonate
-
Woodward's reagent K
N-ethylmaleimide
-
-
o-Iodosobenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-Mercuriphenylsulfonate
-
-
phosphate
-
product inhibition
phosphate
-
substrate inhibition above 10 mM
Pyrimidine acyclonucleosides
-
competitive
-
ribose 1-phosphate
-
-
ribose 1-phosphate
-
product inhibition
ribose 1-phosphate
-
inhibition above 0.6 mM
tetramethylene acyclouridine
-
-
thymidine 5-monophosphate
-
-
Uracil
-
product inhibition
Uracil
-, Q16831
product inhibition pattern, noncompetitive versus uridine and phosphate, overview
Uracil
-
product inhibition, oncompetitive with respect to uridine and phosphate
uridine
-
product inhibition
uridine
-
substrate inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Triton X-100
-
0.1%, stimulates enzyme of isolated plasma membrane
uridine
-
mRNA and protein levels are up-regulated by uridine
additional information
-
UPase expression is up-regulated by glucose deprivation in mRNA as well as protein levels
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.13
-
2'-deoxyuridine
-
-
0.756
-
5'-deoxy-5-fluorouridine
-
-
0.1
-
5-bromodeoxyuridine
-
-
0.03
-
5-Bromouridine
-
-
0.427
-
5-fluoro-2'-deoxyuridine
Q95045
pH 7.4, 37C
0.036
-
5-fluorouracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from liver
0.046
-
5-fluorouracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from colon tumor
0.06
-
5-fluorouracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from colon tumor
0.024
-
5-fluorouridine
Q95045
pH 7.4, 37C
0.07
-
5-methyluridine
-
-
0.248
-
5-methyluridine
-
pH 7.0, 90C
4
-
5-methyluridine
-
-
0.02
-
alpha-D-ribose-1-phosphate
-
cosubstrate: 5-fluorouracil, enzyme from liver
0.03
-
alpha-D-ribose-1-phosphate
-
cosubstrate: uracil, enzyme from liver
0.038
-
alpha-D-ribose-1-phosphate
-
cosubstrate: 5-fluorouracil, enzyme from colon tumor
0.04
-
alpha-D-ribose-1-phosphate
-
cosubstrate: 5-fluorouracil, enzyme from colon tumor
0.087
-
alpha-D-ribose-1-phosphate
-
cosubstrate: uracil, enzyme from colon tumor
0.3
-
deoxyuridine
Q95045
pH 7.4, 37C
0.71
-
deoxyuridine
-
-
0.076
-
phosphate
-
-
0.12
-
phosphate
-
-
0.13
-
phosphate
-
-
0.202
-
phosphate
-
-
0.279
-
phosphate
-
-
0.806
-
phosphate
-
-
2.9
-
phosphate
-
-
3.9
-
phosphate
-
-
0.017
-
ribose 1-phosphate
-
-
0.05
-
ribose 1-phosphate
-
-
0.076
-
ribose 1-phosphate
-
-
0.088
-
ribose 1-phosphate
-
-
0.14
-
ribose 1-phosphate
-
-
0.073
-
thymidine
Q95045
pH 7.4, 37C
0.11
-
thymidine
-
-
0.148
-
thymidine
-
-
0.204
-
Uracil
-
-
0.209
-
Uracil
-
-
0.36
-
Uracil
-
-
0.367
-
Uracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from colon tumor
0.485
-
Uracil
-
cosubstrate: alpha-D-ribose-1-phosphate, enzyme from liver
0.016
-
uridine
-
-
0.033
-
uridine
-
-
0.064
-
uridine
-
-
0.076
-
uridine
Q95045
pH 7.4, 37C
0.085
-
uridine
Q8I3X4
pH 7.5, 25C
0.143
-
uridine
-
-
0.189
-
uridine
-
-
0.2417
-
uridine
-
L-UrdPase transfected lysates
0.242
-
uridine
-
-
0.615
-
uridine
-
pH 7.0, 90C
0.7
-
uridine
-
at 40C
0.76
-
uridine
-
-
0.91
-
uridine
-
-
1.8
-
uridine
-
at 60C
3.8
-
uridine
-
-
0.005
-
Inosine
Q8I3X4
pH 7.5, 25C
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-, Q16831
steady-state kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
56
-
5-methyluridine
-
pH 7.0, 90C
150
-
uridine
-
pH 7.0, 90C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
230
-
5-methyluridine
-
pH 7.0, 90C
3184
74
-
Inosine
Q8I3X4
pH 7.5, 25C
167
0.306
-
uridine
Q8I3X4
pH 7.5, 25C
261
240
-
uridine
-
pH 7.0, 90C
261
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.027
-
1-((2-pyrrolidine-1-yl)ethyl)uracil
Q8I3X4
pH 7.5, 25C
0.0027
-
1-(1',3'-dihydroxy-2'-propoxy)methyl-5,6-tetramethyleneuracil
-
-
0.00007
-
1-(1',3'-dihydroxy-2'-propoxy)methyl-5-benzyluracil
-
-
0.109
-
2',3'-Dideoxy-5-ethyluridine
-
-
1.003
-
2'-Deoxylyxofuranosyl-5-ethyluracil
-
-
0.000025
-
2,2'-Anhydro-5-ethyluridine
-
-
0.00007
-
2,2'-Anhydro-5-ethyluridine
-
-
0.014
-
2,3'-anhydro-5-ethyluridine
-
-
0.005
-
2-deoxyglycosylthymine
-
-
0.225
-
3'-Azido-2',3'-dideoxy-5-ethyluridine
-
-
0.056
-
3'-Azido-2',3'-dideoxy-5-methyluridine
-
-
0.448
-
3'-Bromo-2',3'-dideoxy-5-ethyluridine
-
-
0.21
-
3'-Chloro-2',3'-dideoxy-5-ethyluridine
-
-
0.361
-
3'-Chloro-2',3'-dideoxy-5-methyluridine
-
-
0.006
-
3-((2-pyrrolidine-1-yl)ethyl)uracil
Q8I3X4
pH 7.5, 25C
1.36
-
3-O-methyl-alpha-D-glucopyranose
-
-
0.000018
-
5-(3'-Benzyloxybenzyl)-1-[(1'-aminomethyl-2'-hydroxyethoxy)methyl]uracil
-
-
0.000098
-
5-benzylacyclouridine
-
in 50 mM Tris, 1 mM EDTA, pH 7.4, at 37C
0.0043
-
5-benzylacyclouridine
-
-
0.0073
-
5-benzylacyclouridine
-
-
0.013
-
5-bromoacyclouridine
-
-
0.014
-
5-fluoroacyclouridine
-
-
0.03
-
5-iodoacyclouridine
-
-
0.00068
-
5-m-benzyloxybenzyl acyclouridine
-
-
0.003
-
Acyclothymidine
-
-
0.015
-
acyclouridine
-
-
0.034
-
alpha-D-ribose 1-phosphate
-, Q16831
pH 7.4, 37C, versus uridine
0.494
-
alpha-D-ribose 1-phosphate
-, Q16831
pH 7.4, 37C, versus phosphate
3.5
-
alpha-D-ribose 1-phosphate
-
-
0.07
-
N-ethyl-5-phenylisoxazolium-3'-sulfonate
-
-
2.1
-
N-ethyl-5-phenylisoxazolium-3'-sulfonate
-
addition of uridine
2.5
-
N-ethyl-5-phenylisoxazolium-3'-sulfonate
-
addition of uracil
0.0088
-
tetramethylene acyclouridine
-
-
0.05
-
Uracil
-, Q16831
pH 7.4, 37C, versus uridine
0.137
-
Uracil
-, Q16831
pH 7.4, 37C, versus phosphate
1.45
-
Uracil
-
-
0.047
-
uridine
-
-
0.107
-
Arabinofuranosyl-5-ethyluracil
-
-
additional information
-
additional information
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1.44
-
Q57VZ2, -
substrate deoxyuridine, pH 6.5
2.75
-
Q57VZ2, -
substrate uridine, pH 7.5
7.7
-
-, Q16831
purified recombinant enzyme
89.6
-
-
-
100
120
-
-
182.8
-
-
-
636
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
Q57VZ2, -
pH dependence of enzyme activities with different substrates, overview
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
-
-
deoxyuridine phosphorolysis
6.5
-
Q57VZ2, -
with substrate deoxyuridine
6.9
-
-
deoxynucleoside phosphorolysis
7.3
-
-
uridine phosphorolysis
7.4
-
-
assay at
7.4
-
-
phosphorolysis of ribonucleosides and uracil arabinoside
7.5
-
-
-
7.5
-
Q57VZ2, -
with substrate uridine
7.5
-
-
assay at
7.6
-
-, Q16831
recombinant enzyme
8.2
-
-
-
8.2
-
-
reverse assay, uridine phosphorolysis
8.5
-
-
uridine synthesis
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
9
-, Q16831
recombinant enzyme,m pH profile, overview
5.6
8.4
-
mutant UPL8, more than 60% of maximum activity within
5.8
9
-
pH 5.8: about 50% of activity maximum, pH 9.0: about 40% of activity maximum
6
8.2
-
wild-type, more than 60% of maximum activity within
6
8.5
Q57VZ2, -
pH dependence of enzyme activities with different substrates, overview
6.5
10.5
-
pH 6.5: about 50% of activity maximum, pH 10.5: about 65% of activity maximum
7
7.75
-
pH 6.5: about 70% of activity maximum, pH 8.5: about 25% of activity maximum
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
reverse reaction, assay at
37
-
-
assay at
37
-
-, Q16831
assay at
37
-
-
assay at
40
-
-
wild-type
60
-
-
mutant UPL8
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
40
80
-
40C: about 40% of activity maximum, 80C: about 10% of activity maximum
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
N-butyl-N-(4-hydoxybutyl) nitrosamine (BBN) treatment for 12 weeks induces invasive cancer development in mice
Manually annotated by BRENDA team
-
N-butyl-N-(4-hydoxybutyl) nitrosamine (BBN) treatment for 12 weeks induces superficial cancer development in rats
Manually annotated by BRENDA team
-
12 weeks after initiation of BBN treatment: higher PyNpase level in superficial cancer and hyperplasia compared to controls, 16 and 20 weeks after initiation of BBN treatment: higher PyNpase level in superficial cancer but not in hyperplasia compared to controls
Manually annotated by BRENDA team
-
12, 16 and 20 weeks after initiation of BBN treatment: higher PyNpase level in invasive carcinoma and hyperplasia compared to controls
Manually annotated by BRENDA team
-
negative correlation between UPase expression and the clinical outcome of breast cancer
Manually annotated by BRENDA team
-
colon 26 tumor cells transplanted in BALB/c mice
Manually annotated by BRENDA team
-
brain, liver and heart
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
Q95045
Upase-2 is predominantly expressed in
Manually annotated by BRENDA team
-
Upase-2 is predominantly expressed in
Manually annotated by BRENDA team
additional information
-
present in all human tissue and tumors
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
associated with intermediate filament vimentin in fibroblasts and colon 26 cells
Manually annotated by BRENDA team
-
60-70% of the enzyme exists in the cytosol as a soluble protein
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Actinobacillus succinogenes (strain ATCC 55618 / 130Z)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Shewanella oneidensis (strain MR-1)
Shewanella oneidensis (strain MR-1)
Shewanella oneidensis (strain MR-1)
Streptococcus pyogenes serotype M6 (strain ATCC BAA-946 / MGAS10394)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio fischeri (strain ATCC 700601 / ES114)
Vibrio fischeri (strain ATCC 700601 / ES114)
Vibrio fischeri (strain ATCC 700601 / ES114)
Yersinia pseudotuberculosis serotype I (strain IP32953)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
32000
35000
-
SDS-PAGE
43000
-
-
gel filtration
45000
-
-
gel filtration
56000
-
-
gel filtration
65000
-
-
gel filtration
80000
-
-
non-denaturing PAGE
102500
-
-
disc gel electrophoresis
110000
-
-
gel filtration
130000
-
-
gel filtration, native enzyme
160000
-
-
gel filtration
185300
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 29000, SDS-PAGE
?
Q9K4U1
x * 27500, calculated, x * 28000, SDS-PAGE
dimer
Q16831
isozyme UPP1, the N-terminus of the protein forms a strand-turn-strand structure bracketed by two short helices, structure, overview
hexamer
-
-
hexamer
-
6 * 27500
hexamer
-
6 * 30200, calculated from sequence
hexamer
Aeropyrum pernix DSM 11879
-
6 * 30200, calculated from sequence
-
homodimer
Q57VZ2, -
each monomer is composed of a central 11-stranded mixed beta-sheet surrounded by 14 alpha-helices and two peripheral short, 2-stranded antiparallel beta-sheets
monomer
-
1 * 38000, SDS-PAGE
monomer
-
in the presence of 2 M guanidine hydrochloride
octamer
-
8 * 22200, SDS-PAGE
tetramer
-
4 * 33000
tetramer
-
4 * 26000, SDS-PAGE in presence of 4 M urea and 0.5% 2-mercaptoethanol
tetramer
-
4 * 20000, SDS-PAGE in presence of 2-mercaptoethanol
tetramer
-
4 * 26000, SDS-PAGE in presence of 6 M urea, without 2-mercaptoethanol
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hanging drop vapor diffusion method
-
hanging-drop vapour-diffusion method, crystals of thymidine phosphate complex, 2'-deoxyuridine complex, 5-fluorouracil ribose 1-phosphate complex and native enzyme form
-
hanging-drop vapour-diffusion method, structure at 2.0 A resolution
-
hanging-drop vapour-diffusion method, structures of 5-benzylacyclouridine, 5-phenylthioacyclouridine, 5-phenylselenylacyclouridine, 5-m-benzyloxybenzyl acyclouridine and 5-m-benzyloxybenzyl barbituric acid acyclonucleoside bound to the active site of the enzyme, resolutions ranging from 1.95 to 2.3 A
-
free enzyme and enzyme in complex with inhibitor 5-benzylacyclouridine, 3 mg/ml protein in absence or presence of 1 mM inhibitor from 17% PEG 3350, 100 mM Bis-Tris buffer, pH 5.5, 300 mM KCl, and 30 mM MgCl2, or for the ligand-free ezyme crystals from 1.2 M (NH4)2SO4, 100 mM Bis-Tris buffer pH 5.5, with 1-2% MPD, with 2-3 mg/ml protein, X-ray diffraction structure determination and analysis at 2.3 A and 1.9 A resolution, respectively
Q16831
in complex with 5-fluorouridine, to 2.3 A resolution. The dimeric enzyme is capable of a large hinge motion between its two domains, facilitating ligand exchange and explaining observed cooperativity between the two active sites in binding phosphate-bearing substrates. A loop toward the back end of the uracil binding pocket flexibly adjusts to the varying chemistry of different compounds through an induced-fit association mechanism
Q16831
two crystallographic structures of human isoform UPP2 in distinctly active and inactive conformations, to 2.0 and 1.54 A resolution, respectively. The structures reveal that a conditional intramolecular disulfide bridge can form within the protein that dislocates critical phosphate-coordinating arginine residue R100 away from the active site, disabling the enzyme. The state of the disulfide bridge has further structural consequences for one face of the enzyme that suggest UPP2 may have additional functions in sensing and initiating cellular responses to oxidative stress
O95045
modeling of the inhibitors 1-((2-pyrrolidine-1-yl)ethyl)uracil and 3-((2-pyrrolidine-1-yl)ethyl)uracil into the active site of the protein, PDB entry 1NW4, by superposition of the uracil ring and the purine ring of Immucillin-H. Both compounds can fit adequately in the active site. In both cases the uracil base is predicted to be oriented in the nucleoside binding pocket by a pi-stacking similar to the purine base of Immucillin-H. The N1 of the uracil base in 1-((2-pyrrolidine-1-yl)ethyl)uracil and the N3 of the uracil base in 3-((2-pyrrolidine-1-yl)ethyl)uracil roughly superimpose with the C4 of Immucillin-H
Q8I3X4
complexed with 2,2-anhydrouridine, phosphate and potassium ions at 1.86 A resolution. The monomer is an alpha/beta-class polypeptide with a trilayer alpha/beta/alpha sandwich architecture. The potassium ion is located in the intermonomeric region of each homodimer on the local axis of second order of point group 32. The side chains of Glu49B and Ser73B and the carbonyl O atom of Ile69B in the B subunit, as well as symmetrical residues from the D subunit of the BD homodimer, coordinate K+. The residues in the phosphate binding site are Arg30B, Arg91B, Thr94B and Gly26B from the B subunit, and Arg48D from the D subunit
-
enzyme in complex with 5-fluorouracil, hanging-drop vapour-diffusion method, 0.5 ml of reservoir solution containing 0.34 ml 0.1 M Tris-maleate/NaOH buffer, pH 5.5, and 0.16 ml 40% w/v PEG 3350 is mixed with 2 ml protein solution containing 11.3 mg/ml enzyme in 10 mM Tris-HCl buffer, pH 7.3, 0.002 ml H2O, 0.0013 ml reservoir solution, 0.002 ml 100 mM 5-fluorouracil, and 0.0003 ml 2-propanol, 21C, 1-2 weeks, X-ray diffraction structure determination and analysis at 2.2 A resolution, modeling
-
hanging drop vapour-diffusion method, 2.5 A resolution
-
hanging-drop vapour-diffusion method with PEG as precipitant, 2.9 A resolution
-
in complex with 5-fluorouridine, to 2.2 A resolution. The quaternary structure is represented by a hexamer comprised of six identical subunits. The packing of subunits in the hexamer can be described by the symmetry point group L33L2. The main structural and functional unit in the ligand-free state is a homodimer.The hexameric structure is formed by three homodimers with hydrophobic and hydrogen-bond interactions
-
in complex with with the inhibitor 2,2'-anhydrouridine, the substrate phosphate, and with both the inhibitor 2,2'-anhydrouridine and the substrate phosphate, to 2.38, 1.5 and 1.75 A resolution, respectively. The presence of the phosphate ion in the phosphate-binding site substantially changes the orientations of the side chains of the amino-acid residues Arg30, Arg91, and Arg48 coordinated to this ion. The highly flexible loop L9 is unstable
-
to a resolution of 1.9 A from crystals of the free form grown on earth, 1.6 A from crystals of the complex with uridine and 0.95 A from crystals of the free form grown under microgravity. All crystals belong to the space group P21 and have similar unit-cell parameters
C7EWM3
free selenomethionine-labeled enzyme, or enzyme in complex with uridine, X-ray diffraction structure determination and analysis at 2.7 A and 1.44 A resolution, respectively
Q57VZ2, -
in complex with thymidine, crystals diffrat to 2.1 A resolution, space group P21
Q9K4U1
in silico model of the complex with 5-fluorouracil. The quaternary structure is represented by a hexamer comprised of six identical subunits. The packing of subunits in the hexamer can be described by the symmetry point group L33L2. The hexameric structure of the complex is stabilized by hydrophobic interactions and hydrogen bonds between the amino-acid residues of adjacent homodimers
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3
9
-
pH stability ranging from pH 3.0 to pH 9.0
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
1 month, 20% loss of activity
55
-
-
40 min, 95% loss of activity
55
-
Q57VZ2, -
inactivation after 50 min in presence of 2 mM EGTA, 60% of maximal activity remaining after 90 min in presence of Ca2+
60
-
-
half-life: around 1 week
60
-
-
20 min, complete loss of activity
65
-
-
aglycone substrates, nucleoside substrates, phosphate or pentose 1-phosphate ester substrates stabilize against heat inactivation
75
-
-
1 h, 3.7% residual activity for wild-type, 80.2% residual activity for mutant UPL8
90
-
-
after incubation for 60 min at 90 C, the enzyme remains 100% active
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
aglycone substrates, nucleoside substrates, phosphate or pentose 1-phosphate ester substrates stabilize against heat inactivation
-
use of dithiothreitol and glycerol is necessary for stabilization during purification
-
much less stable in Tris buffer than in phosphate buffer
-
Ca2+ or EGTA stabilize the enzyme
Q57VZ2, -
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-73C, stable for at least 3 months, purified enzyme
-
-73C, stable for at least 6 months, crude extract
-
-20C, stable for 6 months
-
5C, 90% loss of activity after 3-4 days
-
-20C, stable for at least 2 weeks
-
-40C, 0.05 M potassium phosphate buffer, pH 7.0, 10 mM 2-mercaptoethanol, 1 mM EDTA, 10% loss of activity after 6 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
homogeneity
-
near homogeneity
-
phosphorylase type I
-
recombinant N-terminally His6-tagged UPP1 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
Q16831
recombinant UP1 3.8fold from Escherichia coli strain Rosetta (DE3)
-, Q16831
recombinant enzyme from Escherichia coli strain BL21(DE3) by hydrophobic interaction and anion exchange chromatography to 96% homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expression in Escherichia coli, the native apUP protein without fusion tags is actively expressed, and about 50% of the protein is found in the soluble fraction of the cell lysate
-
-
O95045
expressed in Colo-320TP1 and C26A cells
-
expression in Escherichia coli as a fusion protein to glutathione-S-transferase
Q95045
expression of the N-terminally His6-tagged UPP1 in Escherichia coli strain BL21(DE3)
Q16831
expression of UP1 in Escherichia coli strain Rosetta (DE3)
-, Q16831
fusion protein with maltose-binding protein
-
expression in Escherichia coli strain BL21(DE3)
-
expression in Escherichia coli
Q9K4U1
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the peroxisome proliferator-activated receptor gamma coactivator-1alpha induces the enzyme in cancer cells via binding of a nuclear receptor, leading to enhanced antiproliferative activity of 5-deoxy-5-fluorouridine, overview. The activation is abolished by XCT790, i.e. 3-[4-(2,4-bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide. Molecular mechanisms, overview
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C206_A207insGVPLC
-
inactive and insoluble mutant protein
E196A
-
complete loss of uridine phosphorylase activity
E198D
-
complete loss of uridine phosphorylase activity
E198G
-
complete loss of uridine phosphorylase activity
E198Q
-
complete loss of uridine phosphorylase activity
E79-E80insGVPLE
-
inactive mutant protein
F162A
-
mutation causes a drastic decrease in uridine phosphorylase activity
G174_R175insRGTPG
-
134% of the activity of the wild-type enzyme
H8A
-
mutation lowers the activity by 20%
I102_N103insGVPHI
-
inactive and insoluble mutant protein
I69A
-
mutation does not decrease activity
I98_Q99insRGTPI
-
inactive and insoluble mutant protein
K181_G182insGGTPK
-
67% of the activity of the wild-type enzyme
L9_G10insGVPHL
-
139% of the activity of the wild-type enzyme
M197A
-
low activity conserved
R30A
-
complete loss of uridine phosphorylase activity
R30K
-
very low activity
R91A
-
complete loss of uridine phosphorylase activity
R91K
-
very low activity
S159_D160insGGTPS
-
inactive mutant protein
S183_M184insMGYPS
-
54% of the activity of the wild-type enzyme
S183_M184insRGTPS
-
117% of the activity of the wild-type enzyme
T12_K13insGVPLT
-
132% of the activity of the wild-type enzyme
T52_W53insWGTPT
-
inactive mutant protein
T67_G68insGGTPT
-
inactive mutant protein
T94A
-
mutation causes a drastic decrease in uridine phosphorylase activity
V192_M193insMGYPV
-
inactive mutant protein
V31_E32insGVPRV
-
inactive and insoluble mutant protein
V42_K43insKGYPV
-
as active as the wild-type enzyme
W196D
-
mutant enzyme is still partially active
Y195A
-
increase in activity
M197S
-
low activity conserved
additional information
-
evolvement of a mutant enzyme UPL8 by iterative saturation mutagenesis. Compared to the wild type enzyme, which has a temperature optimum of 40C and a half-life of 9.89 h at 60C, the selected mutant has a temperature optimum of 60C and a half-life of 17.3 h at 60C. Self-immobilization of the native enzyme as a Spherezyme shows a 3.3fold increase in thermostability while immobilized mutant enzyme shows a 4.4fold increase in thermostability
Y195G
-
mutation causes a drastic decrease in uridine phosphorylase activity
additional information
Q57VZ2, -
90% suppression of enzyme expression by RNAi does not lead to growth inhibition
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dilution of the enzyme preincubated with 2 M guanidine hydrochloride results in partial recovery
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
synthesis
-
two-step efficient synthesis of 5-methyluridine, a intermediate in the synthesis of anti-AIDS drug such as stavudine and zidovudine
synthesis
-
the enzyme is a valuable industrial biocatalysts for high-temperature reactions that produce nucleoside drugs in high yields
synthesis
Aeropyrum pernix DSM 11879
-
the enzyme is a valuable industrial biocatalysts for high-temperature reactions that produce nucleoside drugs in high yields
-
synthesis
-
evolvement of a mutant enzyme by iterative saturation mutagenesis. Compared to the wild type enzyme, which has a temperature optimum of 40C and a half-life of 9.89 h at 60C, the selected mutant has a temperature optimum of 60C and a half-life of 17.3 h at 60C. Self-immobilization of the native enzyme as a Spherezyme shows a 3.3fold increase in thermostability while immobilized mutant enzyme shows a 4.4fold increase in thermostability. Combining the enzyme with the purine nucleoside phosphorylase from Bacillus halodurans allows for synthesis of 5-methyluridine (a pharmaceutical intermediate) from guanosine and thymine in a one-pot transglycosylation reaction. Replacing the wild type uridine phosphorylase with the mutant allows for an increase in reaction temperature to 65C and increased the reaction productivity from 10 to 31 g per l and h
drug development
-, Q16831
UP12 is a target for development of enzyme inhibitors for cancer chemotherapy, design of inhibitors is intended to boost endogenous uridine levels to rescue normal tissues from the toxicity of fluoropyrimidine nucleoside chemotherapeutic agents, such as capecitabine and 5-fluorouracil.
medicine
-
the paired expression level of the uridine phosphorylase gene in gastric cancer is a possible prognostic marker for patients with 5-fluorouracil treatment
medicine
-
uridine phosphorylase plays an important role in the antineoplastic activity of 5-fluorouracil and in the anabolism of its oral prodrug, capecitabine, through the conversion of 5'-deoxy-5-fluorouridineinto 5-fluorouracil. TNF-alpha efficiently induces UPase gene expression through a NF-kappaB subunit p65-dependent pathway enhancing cell sensitivity to 5'-deoxy-5-fluorouridine. The elucidation of this regulation mechanism may aid in the clinical use of 5-fluorouracil-based chemotherapy