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Information on EC 3.5.4.10 - IMP cyclohydrolase and Organism(s) Homo sapiens

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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
itga2, imp cyclohydrolase, impch, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/imp cyclohydrolase, inosine monophosphate cyclohydrolase, purh2, aicar transformylase/imp cyclohydrolase, inosinicase, mthpuro, af1811, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
AICAR-FT/IMP-CHase
-
IMP synthetase
-
-
-
-
IMPCHase
-
-
-
-
inosinate cyclohydrolase
-
-
-
-
inosine monophosphate cyclohydrolase
-
-
-
-
inosinicase
-
-
-
-
ITGA2
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
show the reaction diagram
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
IMP 1,2-hydrolase (decyclizing)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9013-81-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide
?
show the reaction diagram
5-formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide
IMP + H2O
show the reaction diagram
5-formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide + H2O
?
show the reaction diagram
catalyzation of the final two steps of de novo purine biosynthesis pathway
-
-
?
5-formamidoimidazole-4-carboxamide
hypoxanthine + H2O
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5-formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide
?
show the reaction diagram
5-formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide + H2O
?
show the reaction diagram
catalyzation of the final two steps of de novo purine biosynthesis pathway
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2'-deoxy-AMP
-
decreased IMP cyclohydrolase activity by 10-50%
2-chloroinosine 5'-monophosphate
-
potent inhibitor
2-flouroinosine 5'-monophosphate
-
IC50-value in cell culture 0.0049 mM; potent inhibitor
2-fluoroadenine arabinoside 5'-monophosphate
2-mercaptoinosine 5'-monophosphate
-
most potent competitive inhibitor, precursor of GMP in the purine pathway
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
-
decreased IMP cyclohydrolase activity by 10-50%
6-mercaptopurine riboside 5'-monophosphate
adenosine N1-oxide 5'-monophosphate
AMP
-
decreased IMP cyclohydrolase activity by 10-50%
GMP
-
decreased IMP cyclohydrolase activity by 10-50%
IMP
-
decreased IMP cyclohydrolase activity by 10-50%
N-succino-AMP
-
decreased IMP cyclohydrolase activity by 10-50%
N2-acetyl-2'deoxyguanosine 5'-monophosphate
-
decreased IMP cyclohydrolase activity by 10-50%
N6-(carboxymethyl)adenosine 5'-monophosphate
-
strong competitive inhibitor
xanthosine 5'-monophosphate
-
strong competitive inhibitor
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KCl
higher activity in buffers containing 50 mM
NaCl
higher activity in buffers containing 150 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0009 - 0.115
5-Formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.014 - 8.6
5-Formamido-1-(5-phosphoribosyl)imidazole-4-carboxamide
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0049
2-flouroinosine 5'-monophosphate
Homo sapiens
-
IC50-value in cell culture 0.0049 mM
0.0002
2-fluoroadenine arabinoside 5'-monophosphate
Homo sapiens
-
IC50-value in cell culture 0.0002 mM
0.0075
6-mercaptopurine riboside 5'-monophosphate
Homo sapiens
-
IC50-value in cell culture 0.0075 mM
0.0000011
adenosine N1-oxide 5'-monophosphate
Homo sapiens
-
IC50-value in cell culture 0.0011 microM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.8
extract from Escherichia coli expression mutants after several pufification steps
additional information
proteomic approach to identify phophorylated proteins with a pathogenic role in transformation mediated by anaplastic lymphoma kinase (ALK), profiling of tyrosine-phosphorylation, mass spectrometry, anti-phosphotyrosine protein immunoprecipitation, posttranslational modification of the bifunctional 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) formyltransferase/inosine monophosphate (IMP) cyclohydrolase (AICAR-FT/IMP-CHase, ATIC) by phosphorylation, enzyme is a direct target of anaplastic lymphoma kinase (ALK), phoshorylation increases enzyme activity posttranslational modification of a key purine synthesis enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
ALCL cell line TS, Sup-M2 cells, JB-6 cells, SU-DHL1 cells
Manually annotated by BRENDA team
immunoprecipitated from
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
impact of the ITGA2 gene polymorphism C807T on gastric cancer risk, overview. Increased risk of gastric cancer associated with the polymorphism is pronounced in rural subjects, but not in urban subjects
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PUR9_HUMAN
592
0
64616
Swiss-Prot
other Location (Reliability: 2)
V9HWH7_HUMAN
592
0
64616
TrEMBL
other Location (Reliability: 2)
B4DP06_HUMAN
533
0
58662
TrEMBL
other Location (Reliability: 5)
B2R7P8_HUMAN
592
0
64635
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
62100
-
2 * 62100, protein mobility assay
64425
2 * 64425, open reading frame, polypeptide of 591 amino acids, 81% similar to chicken IMPCHase, truncation mutant, IMPCHase activity located within the NH2-terminal 223 amino acids
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
phophorylation increases enzyme activity
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with transformylase inhibitors BW1540 and BW2315
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C807T
-
naturally occuring polymorphism involved in gastric cancer development
D125A
D125E
D125N
K137A
K137R
K246R
natural mutation observed in female infant patient with lack in transformylase activity and about 40% residual enzymic activity, showing massive excretion of 5-amino-4-imidazolecarboxamide riboside, dysmorphic features, severe neurological defects, and congenital blindness. Recombinant protein with K426R mutation completely lacks AICAR transformylase activity
Y104A
Y104A/D125A
Y104F
Y104F/D125A
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
780fold to apparent homogeneity
-
near to homogeneity from Escherichia coli expression mutants
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
gene ITGA2, genotyping of 614 male subjects, 1:1 ratio of gastric cancer patients and healthy controls, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
determination of differentially expressed genes in HT-29 cells, both after short treatment with methotrexate and after the resistance to methotrexate has been established. Enzyme as well as survivin and inosine monophosphate dehydrogenase type II are upregulated
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Szabados, E.; Hindmarsh, E.J.; Phillips, L.; Duggleby, R.G.; Christopherson, R.I.
5-Aminoimidazole-4-carboxamide ribotide transformylase-IMP cyclohydrolase from human CCRF-CEM leukemia cells: purification, pH dependence and inhibitors
Biochemistry
33
14237-14245
1994
Homo sapiens
Manually annotated by BRENDA team
Christopherson, R.I.; Williams, N.K.; Schoettle, S.L.; Szabados, E.; Hambley, T.W.; Manthey, M.K.
Inhibitors of dihydroorotase, amidophosphoribosyltransferase and IMP cyclohydrolase as potential drugs
Biochem. Soc. Trans.
23
888-893
1995
Homo sapiens
Manually annotated by BRENDA team
Rayl, E.A.; Moroson, B.A.; Beardsley, G.P.
The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping
J. Biol. Chem.
271
2225-2233
1996
Homo sapiens (P31939), Homo sapiens
Manually annotated by BRENDA team
Szabados, E.; Manthey, M.K.; Wilson, P.K.; Christopherson, R.I.
Inosine-5'-monophosphate analogues as inhibitors of human IMPcyclohydrolase and cellular growth
Biochem. Mol. Biol. Int.
44
617-623
1998
Homo sapiens
Manually annotated by BRENDA team
Vergis, J.M.; Bulock, K.G.; Fleming, K.G.; Beardsley, G.P.
Human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase. A bifunctional protein requiring dimerization for transformylase activity but not for cyclohydrolase activity
J. Biol. Chem.
276
7727-7733
2001
Homo sapiens
Manually annotated by BRENDA team
Bulock, K.G.; Beardsley, G.P.; Anderson, K.S.
The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase): A surprising lack of substrate channeling
J. Biol. Chem.
277
22168-22174
2002
Homo sapiens
Manually annotated by BRENDA team
Wolan, D.W.; Cheong, C.G.; Greasley, S.E.; Wilson, I.A.
Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor
Biochemistry
43
1171-1183
2004
Homo sapiens (P31939), Homo sapiens
Manually annotated by BRENDA team
Cheong, C.G.; Wolan, D.W.; Greasley, S.E.; Horton, P.A.; Beardsley, G.P.; Wilson, I.A.
Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates
J. Biol. Chem.
279
18034-18045
2004
Homo sapiens (P31939), Homo sapiens
Manually annotated by BRENDA team
Vergis, J.M.; Beardsley, G.P.
Catalytic mechanism of the cyclohydrolase activity of human aminoimidazole carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase
Biochemistry
43
1184-1192
2004
Homo sapiens
Manually annotated by BRENDA team
Marie, S.; Heron, B.; Bitoun, P.; Timmerman, T.; Van Den Berghe, G.; Vincent, M.F.
AICA-ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC
Am. J. Hum. Genet.
74
1276-1281
2004
Homo sapiens (P31939), Homo sapiens
Manually annotated by BRENDA team
Penuelas, S.; Noe, V.; Ciudad, C.J.
Modulation of IMPDH2, survivin, topoisomerase I and vimentin increases sensitivity to methotrexate in HT29 human colon cancer cells
FEBS J.
272
696-710
2005
Homo sapiens (P31939), Homo sapiens
Manually annotated by BRENDA team
Boccalatte, F.E.; Voena, C.; Riganti, C.; Bosia, A.; DAmico, L.; Riera, L.; Cheng, M.; Ruggeri, B.; Jensen, O.N.; Goss, V.L.; Lee, K.; Nardone, J.; Rush, J.; Polakiewicz, R.D.; Comb, M.J.; Chiarle, R.; Inghirami, G.
The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL
Blood
113
2776-2790
2009
Homo sapiens (P31939)
Manually annotated by BRENDA team
Chen, X.; Zhao, J.; Xu, X.; Zeng, R.
Screening and cloning of IMP cyclohydrolase from a metagenomic cosmid library of a deep-sea sediment sample
Chin. J. Appl. Environ. Biol.
17
855-859
2011
Homo sapiens
-
Manually annotated by BRENDA team