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MetaCyc Enzyme: inositol-polyphosphate kinase/phosphatase

Gene: ITPK1 Accession Number: HS02123 (MetaCyc)

Synonyms: ITRPK1

Species: Homo sapiens

Summary:
This enzyme was originally purified from calf brain as inositol 1,3,4-trisphosphate 5/6-kinase, and a cDNA encoding the enzyme was isolated at the time [Wilson96]. Homologous human cDNAs were obtained from brain and breast cDNA libraries, and it was shown that the enzyme also phosphorylates (and inactivates) the second messenger D-myo-inositol (3,4,5,6)-tetrakisphosphate [Yang00].

The gene was cloned and expressed in Escherichia coli, and the recombinant protein was purified and characterized. Kinetic data suggested that D-myo-inositol (3,4,5,6)-tetrakisphosphate and D-myo-inositol (1,3,4)-trisphosphate compete for phosphorylation in vivo [Yang00]. D-myo-inositol (1,3,4)-trisphosphate actually acts in vivo as a specific regulator of cellular signaling by D-myo-inositol (3,4,5,6)-tetrakisphosphate [Yang99c].

A later study described several additionals functions for the enzyme, including a myo-inositol-1,3,4,5,6-pentakisphosphate 1-phosphatase activity [Ho02]. The authors acknowledged the fact that it is exceptional for a single enzyme to catalyze two opposing signaling reactions (1-kinase/1-phosphatase) under physiological conditions. D-myo-inositol (1,3,4)-trisphosphate was shown to be an activator of the 1-phosphatase activity [Ho02].

The enzyme also demonstrated a phosphomutase activity, catalyzing an exchange between D-myo-inositol (1,3,4,5)-tetrakisphosphate and D-myo-inositol (1,3,4,6)-tetrakisphosphate, and the control over whether the enzyme catalyzes kinase or phosphatase reaction appears to be complex, and not dictated by the ATP/ADP ratio [Ho02].

The enzyme was shown top be stereospecific, and does not accept D-myo-inositol (1,4,5,6)-tetrakisphosphate as a substrate [Riley06a].

Map Position: [87,219,967 <- 87,398,911]

Molecular Weight of Polypeptide: 45.621 kD (from nucleotide sequence), 48.0 kD (experimental) [Yang00 ]

Unification Links: ArrayExpress:Q13572 , DIP:DIP-60016N , Entrez-Nucleotide:U51336 , Mint:MINT-1463374 , PhosphoSite:Q13572 , Pride:Q13572 , Protein Model Portal:Q13572 , SMR:Q13572 , String:9606.ENSP00000267615 , UniProt:Q13572

Relationship Links: InterPro:IN-FAMILY:IPR008656 , InterPro:IN-FAMILY:IPR011761 , Panther:IN-FAMILY:PTHR14217 , PDB:Structure:2ODT , PDB:Structure:2Q7D , PDB:Structure:2QB5 , Pfam:IN-FAMILY:PF05770 , Prosite:IN-FAMILY:PS50975

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Credits:
Created 21-Oct-2009 by Caspi R , SRI International


Enzymatic reaction of: inositol 1,3,4-triphosphate 5 kinase (inositol-polyphosphate kinase/phosphatase)

EC Number: 2.7.1.159

D-myo-inositol (1,3,4)-trisphosphate + ATP <=> D-myo-inositol (1,3,4,5)-tetrakisphosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Kinetic Parameters:

Substrate
Km (μM)
Citations
D-myo-inositol (1,3,4)-trisphosphate
0.3
[Yang00]


Enzymatic reaction of: inositol 1,3,4-triphosphate 6 kinase (inositol-polyphosphate kinase/phosphatase)

EC Number: 2.7.1.159

D-myo-inositol (1,3,4)-trisphosphate + ATP <=> D-myo-inositol (1,3,4,6)-tetrakisphosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis , D-myo-inositol (1,4,5,6)-tetrakisphosphate biosynthesis , 1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)

Kinetic Parameters:

Substrate
Km (μM)
Citations
D-myo-inositol (1,3,4)-trisphosphate
0.3
[Yang00]


Enzymatic reaction of: inositol-tetrakisphosphate 1-kinase (inositol-polyphosphate kinase/phosphatase)

EC Number: 2.7.1.134

D-myo-inositol (3,4,5,6)-tetrakisphosphate + ATP <=> D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis

Kinetic Parameters:

Substrate
Km (μM)
Citations
D-myo-inositol (3,4,5,6)-tetrakisphosphate
0.1
[Yang00]


Enzymatic reaction of: myo-inositol-1,3,4,5,6-pentakisphosphate 1-phosphatase (inositol-polyphosphate kinase/phosphatase)

EC Number: 3.1.3.-

D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O <=> D-myo-inositol (3,4,5,6)-tetrakisphosphate + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis

Activators (Unknown Mechanism): D-myo-inositol (1,3,4)-trisphosphate [Ho02]


Enzymatic reaction of: inositol tetraphosphate phosphomutase (inositol-polyphosphate kinase/phosphatase)

D-myo-inositol (1,3,4,6)-tetrakisphosphate <=> D-myo-inositol (1,3,4,5)-tetrakisphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.

Exons/Introns:

Schematic showing introns, exons and/or isoforms of ITPK1


References

Ho02: Ho, M. W.K., Yang, X., Carew, M.A., Zhang, T, Hua, L., Kwon, Y., Chung, S., Adelt, S., Vogel, G., Riley, A.M., Potter, B.V.L., Shears, S.B. (2002). "Regulation of Ins(3,4,5,6)P4 Signaling by a Reversible Kinase/Phosphatase." Curr. Biol. 12(6): 477-482.

Riley06a: Riley AM, Deleu S, Qian X, Mitchell J, Chung SK, Adelt S, Vogel G, Potter BV, Shears SB (2006). "On the contribution of stereochemistry to human ITPK1 specificity: Ins(1,4,5,6)P4 is not a physiologic substrate." FEBS Lett 580(1);324-30. PMID: 16376887

Wilson96: Wilson MP, Majerus PW (1996). "Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme." J Biol Chem 271(20);11904-10. PMID: 8662638

Yang00: Yang X, Shears SB (2000). "Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase." Biochem J 351 Pt 3;551-5. PMID: 11042108

Yang99c: Yang X, Rudolf M, Carew MA, Yoshida M, Nerreter V, Riley AM, Chung SK, Bruzik KS, Potter BV, Schultz C, Shears SB (1999). "Inositol 1,3,4-trisphosphate acts in vivo as a specific regulator of cellular signaling by inositol 3,4,5,6-tetrakisphosphate." J Biol Chem 274(27);18973-80. PMID: 10383396


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Fri Jul 3, 2015, BIOCYC13A.