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Information on EC 2.7.1.159 - inositol-1,3,4-trisphosphate 5/6-kinase and Organism(s) Homo sapiens and UniProt Accession Q13572
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EC Tree
2.7.1.159 inositol-1,3,4-trisphosphate 5/6-kinaseIUBMB Comments
In humans, this enzyme, along with EC 2.7.1.127 (inositol-trisphosphate 3-kinase), EC 2.7.1.140 (inositol-tetrakisphosphate 5-kinase) and EC 2.7.1.158 (inositol pentakisphosphate 2-kinase) is involved in the production of inositol hexakisphosphate (InsP6). InsP6 is involved in many cellular processes, including mRNA export from the nucleus . Yeasts do not have this enzyme, so produce InsP6 from Ins(1,4,5)P3 by the actions of EC 2.7.1.151 (inositol-polyphosphate multikinase) and EC 2.7.1.158 (inositol-pentakisphosphate 2-kinase) . The enzymes from animals and plants also have the activity of EC 2.7.1.134, inositol-tetrakisphosphate 1-kinase.
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Word Map
- 2.7.1.159
-
phytic
- polyphosphate
-
hexakisphosphate
- dehydration
-
itpks
-
2-kinase
- phosphorus
- pentakisphosphate
-
signalosome
-
lipid-independent
-
tnfalpha-induced
- 1,3,4,5,6-pentakisphosphate
-
monophosphatase
-
photomorphogenesis
-
1,4,5-tris-phosphate
- 1,3,4,6-tetrakisphosphate
- phytate
- imp
- ikappabalpha
-
atp-grasp
- agriculture
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(3 overall reactions are displayed. Show all (4)>>)
Synonyms
5/6-kinase, gmitpk2, ositl1, 5/6 kinase, atitpk4, inositol 1,3,4-triphosphate 5/6-kinase, at2g43980, inositol-1,3,4-trisphosphate 5/6-kinase, inositol-1,3,4-trisphosphate kinase, ins(1,3,4)p3 5/6-kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol 1,3,4-trisphosphate 5-phosphotransferase
In humans, this enzyme, along with EC 2.7.1.127 (inositol-trisphosphate 3-kinase), EC 2.7.1.140 (inositol-tetrakisphosphate 5-kinase) and EC 2.7.1.158 (inositol pentakisphosphate 2-kinase) is involved in the production of inositol hexakisphosphate (InsP6). InsP6 is involved in many cellular processes, including mRNA export from the nucleus [2]. Yeasts do not have this enzyme, so produce InsP6 from Ins(1,4,5)P3 by the actions of EC 2.7.1.151 (inositol-polyphosphate multikinase) and EC 2.7.1.158 (inositol-pentakisphosphate 2-kinase) [2]. The enzymes from animals and plants also have the activity of EC 2.7.1.134, inositol-tetrakisphosphate 1-kinase.
CAS REGISTRY NUMBER
COMMENTARY
288307-53-9
-
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
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,5-tetrakisphosphate
lower activity compared to 1D-myo-inositol-1,3,4,6-tetrakisphosphate formation
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,6-tetrakisphosphate
higher activity compared to 1D-myo-inositol-1,3,4,5-tetrakisphosphate formation
-
-
?
1D-myo-inositol-1,3,4,5,6-pentakisphosphate + ADP
1D-myo-inositol-3,4,5,6-tetrakisphosphate + ATP
-
enzyme catalyzes both forward and reverse reaction
putative regulator of Ca2+-activated chloride channels.
-
r
1D-myo-inositol-1,3,4,5-tetrakisphosphate + ATP
1D-myo-inositol-1,3,4,5,6-pentakisphosphate + ADP
-
-
-
-
r
1D-myo-inositol-1,3,4,6-tetrakisphosphate + ATP
1D-myo-inositol-1,3,4,5,6-pentakisphosphate + ADP
-
-
-
-
r
1D-myo-inositol-1,3,4-trisphosphate + ATP
1D-myo-inositol-1,3,4,5-tetrakisphosphate + ADP
-
-
-
-
r
1D-myo-inositol-1,3,4-trisphosphate + ATP
1D-myo-inositol-1,3,4,6-tetrakisphosphate + ADP
-
-
-
-
r
ATP + 1D-myo-inositol-1,3,4,6-tetrakisphosphate
ADP + 1D-myo-inositol-1,3,4,5,6-pentakisphosphate
-
-
-
-
?
ATP + ATF-2
ADP + phosphorylated ATF-2
-
phosphorylation predominantly on serine residues
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
-
substrate of the free enzyme and the COP9 signalosome complex
-
-
?
ATP + p53
ADP + phosphorylated p53
-
substrate of the free enzyme and the COP9 signalosome complex
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,5-tetrakisphosphate
-
-
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,5-tetrakisphosphate
-
5fold lower activity compared to 1D-myo-inositol-1,3,4,6-tetrakisphosphate formation
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,5-tetrakisphosphate
-
substrate of the free enzyme and the COP9 signalosome complex
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,6-tetrakisphosphate
-
-
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,6-tetrakisphosphate
-
5fold higher activity compared to 1D-myo-inositol-1,3,4,5-tetrakisphosphate formation
-
-
?
ATP + 1D-myo-inositol-1,3,4-trisphosphate
ADP + 1D-myo-inositol-1,3,4,6-tetrakisphosphate
-
substrate of the free enzyme and the COP9 signalosome complex
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
-
substrate of the free enzyme and the COP9 signalosome complex, which both show no activity with the 1-79 residue fragment of c-Jun
-
-
?
additional information
?
-
-
regulation of enzymes involved in the inositol phosphate metabolism in human cells, overview
-
-
?
additional information
?
-
-
the enzyme inhibits tumor necrosis factor alpha-induced apoptosis involving the activation of PARP, BID, caspase-3 and caspase-8, but protects not against etoposide- or cycloheximide-induced apotosis, mechanism
-
-
?
additional information
?
-
-
the enzyme associates with the COP9 signalosome, an complex of 8 proteins, by binding to CSN1
-
-
?
additional information
?
-
-
the enzyme is part of the COP9 signalosome complex consisting of 8 proteins
-
-
?
additional information
?
-
-
integration of inositol phosphate signaling pathways via human ITPK1
-
-
?
additional information
?
-
-
enzyme has both phosphatase and kinase activity
-
-
?
additional information
?
-
-
The enzyme can phosphorylate both 1D-myo-inositol-1,3,4-trisphosphate at the 5 or 6 positions and 1D-myo-inositol-3,4,5,6-tetrakisphosphate at the 1 position and can also dephosphorylate 1D-myo-inositol-1,3,4,5,6-pentaakisphosphate to 1D-myo-inositol-3,4,5,6-tetrakisphosphate
-
-
?
additional information
?
-
-
The phenomenon of intersubstrate transfer is only found in the human enzyme, which can use 1D-myo-inositol 1,3,4-trisphosphate to regulate increased cellular concentrations of 1D-myo-inositol-3,4,5,6-tetrakisphosphate
-
-
?
additional information
?
-
-
the various enzyme activities manifested by ITPK1 provide a molecular mechanism that allows the receptor-activated changes in phospholipase C activity and consequent increases in the concentration of 1D-myo-inositol 1,3,4-trisphosphate to regulate the abundance of 1D-myo-inositol-3,4,5,6-tetrakisphosphate
-
-
?
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
1D-myo-inositol-1,3,4,5,6-pentakisphosphate + ADP
1D-myo-inositol-3,4,5,6-tetrakisphosphate + ATP
-
enzyme catalyzes both forward and reverse reaction
putative regulator of Ca2+-activated chloride channels.
-
r
1D-myo-inositol-1,3,4,5-tetrakisphosphate + ATP
1D-myo-inositol-1,3,4,5,6-pentakisphosphate + ADP
-
-
-
-
r
1D-myo-inositol-1,3,4,6-tetrakisphosphate + ATP
1D-myo-inositol-1,3,4,5,6-pentakisphosphate + ADP
-
-
-
-
r
1D-myo-inositol-1,3,4-trisphosphate + ATP
1D-myo-inositol-1,3,4,5-tetrakisphosphate + ADP
-
-
-
-
r
1D-myo-inositol-1,3,4-trisphosphate + ATP
1D-myo-inositol-1,3,4,6-tetrakisphosphate + ADP
-
-
-
-
r
additional information
?
-
-
regulation of enzymes involved in the inositol phosphate metabolism in human cells, overview
-
-
?
additional information
?
-
-
the enzyme inhibits tumor necrosis factor alpha-induced apoptosis involving the activation of PARP, BID, caspase-3 and caspase-8, but protects not against etoposide- or cycloheximide-induced apotosis, mechanism
-
-
?
additional information
?
-
-
integration of inositol phosphate signaling pathways via human ITPK1
-
-
?
additional information
?
-
-
enzyme has both phosphatase and kinase activity
-
-
?
additional information
?
-
-
The enzyme can phosphorylate both 1D-myo-inositol-1,3,4-trisphosphate at the 5 or 6 positions and 1D-myo-inositol-3,4,5,6-tetrakisphosphate at the 1 position and can also dephosphorylate 1D-myo-inositol-1,3,4,5,6-pentaakisphosphate to 1D-myo-inositol-3,4,5,6-tetrakisphosphate
-
-
?
additional information
?
-
-
The phenomenon of intersubstrate transfer is only found in the human enzyme, which can use 1D-myo-inositol 1,3,4-trisphosphate to regulate increased cellular concentrations of 1D-myo-inositol-3,4,5,6-tetrakisphosphate
-
-
?
additional information
?
-
-
the various enzyme activities manifested by ITPK1 provide a molecular mechanism that allows the receptor-activated changes in phospholipase C activity and consequent increases in the concentration of 1D-myo-inositol 1,3,4-trisphosphate to regulate the abundance of 1D-myo-inositol-3,4,5,6-tetrakisphosphate
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
curcumin
-
inhibits both the free enzyme and the COP9 signalosome complex-associated kinase
protein kinase A
-
slight inhibition of enzyme activity with ATF-2 as substrate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CSN1
-
the enzyme associates with the COP9 signalosome, an complex of 8 proteins, by binding to CSN1, activates
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics, recombinant enzyme with CSN1
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5
1D-myo-inositol-1,3,4-trisphosphate
-
pH 7.6, 37°C, in absence of CSN1, first order rate constant
20
1D-myo-inositol-1,3,4-trisphosphate
-
pH 7.6, 37°C, in presence of CSN1, first order rate constant
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
500
-
purified recombinant enzyme from Sf21 cells, with substrate 1D-myo-inositol-1,3,4-trisphosphate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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). ITPK1_HUMAN
414
0
45621
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
isoform ITPK1 can be acetylated by the acetyltransferases CREB-binding protein, CBP, and p300 both in vivo and in vitro and can be deacetylated by mammalian silent information regulator 2, SIRT1. Acetylation of ITPK1 decreases its enzyme activity and protein stability, and inhibits the synthesis of higher phosphorylated forms of inositol polyphosphates in the inositol signaling pathway. The acetylation sites are lysine residues 340, 383, and 410, which are all located on the surface of the protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
enzyme overexpression in HEK-293 cells inhibits TNFalpha-induced activation of caspases-8, -3, and -9, siRNA gene silencing of the enzyme in HeLa cells results in higher susceptibility of the cells to TNFalpha-induced apoptosis
additional information
-
enzyme silencing in HeLa cells decreases the levels of inositol pentakisphosphate and inositol hexakisphosphate, while overexpression in HEK-293 cells increases the levels of InsP4, InsP5, and InsP6, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli by adsorption and calmodulin affinity chromatography
recombinant enzyme from insect Sf21 cells, recombinant enzyme partially from 293 cells by ion exchange chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and N-terminal amino acid sequence determination and analysis, expression as His-tagged enzyme in Escherichia coli
expression in 293 cells, expression in Spodoptera frugiperda Sf21 cells using the baculovirus infection system
-
expression of the enzyme tagged with 6 repeats of Myc at the N-terminus in Spodoptera frugiperda Sf21 cells using the baculovirus infection system, expression of His6-tagged and of FLAG-tagged enzyme in Escherichia coli strain BL21(DE3), co-overexpression of the enzyme with CSN1 in HeLa cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wilson, M.P.; Majerus, P.W.
Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning, and expression of the recombinant enzyme
J. Biol. Chem.
271
11904-11910
1996
Bos taurus, Homo sapiens (Q13572)
Verbsky, J.W.; Chang, S.C.; Wilson, M.P.; Mochizuki, Y.; Majerus, P.W.
The pathway for the production of inositol hexakisphosphate in human cells
J. Biol. Chem.
280
1911-1920
2005
Homo sapiens
Wilson, M.P.; Sun, Y.; Cao, L.; Majerus, P.W.
Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates the transcription factors c-Jun and ATF-2
J. Biol. Chem.
276
40998-41004
2001
Bos taurus, Homo sapiens
Sun, Y.; Wilson, M.P.; Majerus, P.W.
Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1
J. Biol. Chem.
277
45759-45764
2002
Homo sapiens
Sun, Y.; Mochizuki, Y.; Majerus, P.W.
Inositol 1,3,4-trisphosphate 5/6-kinase inhibits tumor necrosis factor-induced apoptosis
J. Biol. Chem.
278
43645-43653
2003
Homo sapiens
Chamberlain, P.P.; Qian, X.; Stiles, A.R.; Cho, J.; Jones, D.H.; Lesley, S.A.; Grabau, E.A.; Shears, S.B.; Spraggon, G.
Integration of inositol phosphate signaling pathways via human ITPK1
J. Biol. Chem.
282
28117-28125
2007
Homo sapiens
Saiardi, A.; Cockcroft, S.
Human ITPK1: a reversible inositol phosphate kinase/phosphatase that links receptor-dependent phospholipase C to Ca2+-activated chloride channels
Sci. Signal.
1
1-3
2008
Homo sapiens
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