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Identification
HMDB Protein ID HMDBP07396
Secondary Accession Numbers
  • 13063
Name Inositol-tetrakisphosphate 1-kinase
Synonyms
  1. Inositol 1,3,4-trisphosphate 5/6-kinase
  2. Inositol-triphosphate 5/6-kinase
  3. Ins(1,3,4)P(3) 5/6-kinase
Gene Name ITPK1
Protein Type Unknown
Biological Properties
General Function Involved in catalytic activity
Specific Function Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain.
Pathways
  • Inositol Metabolism
  • Inositol phosphate metabolism
  • Inositol Phosphate Metabolism
  • Phosphatidylinositol signaling system
Reactions
Adenosine triphosphate + D-myo-Inositol 3,4,5,6-tetrakisphosphate → ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate details
Adenosine triphosphate + Inositol 1,3,4-trisphosphate → ADP + myo-Inositol 1,3,4,5-tetrakisphosphate details
Adenosine triphosphate + Inositol 1,3,4-trisphosphate → ADP + D-myo-Inositol 1,3,4,6-tetrakisphosphate details
Adenosine triphosphate + D-myo-Inositol 3,4,5,6-tetrakisphosphate → ADP + myo-Inositol 1,3,4,5,6-pentakisphosphate details
GO Classification
Biological Process
signal transduction
blood coagulation
inositol trisphosphate metabolic process
Cellular Component
cytosol
Component
cell part
intracellular
Function
inositol tetrakisphosphate kinase activity
ion binding
inositol tetrakisphosphate 1-kinase activity
cation binding
inositol-1,3,4-trisphosphate 5/6-kinase activity
metal ion binding
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
magnesium ion binding
inositol or phosphatidylinositol kinase activity
inositol trisphosphate kinase activity
Molecular Function
magnesium ion binding
ATP binding
inositol tetrakisphosphate 1-kinase activity
inositol-1,3,4-trisphosphate 5-kinase activity
inositol-1,3,4-trisphosphate 6-kinase activity
catalytic activity
hydrolase activity
isomerase activity
Process
inositol phosphate metabolic process
inositol trisphosphate metabolic process
metabolic process
small molecule metabolic process
alcohol metabolic process
polyol metabolic process
inositol metabolic process
Cellular Location Not Available
Gene Properties
Chromosome Location 14
Locus 14q31
SNPs ITPK1
Gene Sequence
>1245 bp
ATGCAGACCTTTCTGAAAGGGAAGAGAGTTGGCTACTGGCTGAGCGAGAAGAAAATCAAG
AAGCTGAATTTCCAGGCCTTCGCCGAGCTGTGCAGGAAGCGAGGGATGGAGGTTGTGCAG
CTGAACCTTAGCCGGCCGATCGAGGAGCAGGGCCCCCTGGACGTCATCATCCACAAGCTG
ACTGACGTCATCCTTGAAGCCGACCAGAATGATAGCCAGTCCCTGGAGCTGGTGCACAGG
TTCCAGGAGTACATCGATGCCCACCCTGAGACCATCGTCCTGGACCCGCTCCCTGCCATC
AGAACCCTGCTTGACCGCTCCAAGTCCTATGAGCTCATCCGGAAGATTGAGGCCTACATG
GAAGACGACAGGATCTGCTCGCCACCCTTCATGGAGCTCACGAGCCTGTGCGGGGATGAC
ACCATGCGGCTGCTGGAGAAGAACGGCTTGACTTTCCCATTCATTTGCAAAACCAGAGTG
GCTCATGGCACCAACTCTCACGAGATGGCTATCGTGTTCAACCAGGAGGGCCTGAACGCC
ATCCAGCCACCCTGCGTGGTCCAGAATTTCATCAACCACAACGCCGTCCTGTACAAGGTG
TTCGTGGTTGGCGAGTCCTACACCGTGGTCCAGAGGCCCTCACTCAAGAACTTCTCCGCA
GGCACATCAGACCGTGAGTCCATCTTCTTCAACAGCCACAACGTGTCAAAGCCGGAGTCG
TCATCGGTCCTGACGGAGCTGGACAAGATCGAGGGCGTGTTCGAGCGGCCGAGCGACGAG
GTCATCCGGGAGCTCTCCCGGGCCCTGCGGCAGGCACTGGGCGTGTCACTCTTTGGCATC
GACATCATCATCAACAACCAGACAGGGCAGCACGCCGTCATTGACATCAATGCCTTCCCA
GGCTACGAGGGCGTGAGCGAGTTCTTCACAGACCTCCTGAACCACATCGCCACTGTCCTG
CAGGGCCAGAGCACAGCCATGGCAGCCACAGGGGACGTGGCCCTGCTGAGGCACAGCAAG
CTTCTGGCCGAGCCGGCGGGCGGCCTGGTGGGCGAGCGGACATGCAGCGCCAGCCCCGGC
TGCTGCGGCAGCATGATGGGCCAGGACGCGCCCTGGAAGGCTGAGGCCGACGCGGGCGGC
ACCGCCAAGCTGCCGCACCAGAGACTCGGCTGCAACGCCGGCGTGTCGCCCAGCTTCCAG
CAGCATTGTGTGGCCTCCCTGGCCACCAAGGCCTCCTCCCAGTAG
Protein Properties
Number of Residues 414
Molecular Weight 45620.645
Theoretical pI 6.161
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Inositol-tetrakisphosphate 1-kinase
MQTFLKGKRVGYWLSEKKIKKLNFQAFAELCRKRGMEVVQLNLSRPIEEQGPLDVIIHKL
TDVILEADQNDSQSLELVHRFQEYIDAHPETIVLDPLPAIRTLLDRSKSYELIRKIEAYM
EDDRICSPPFMELTSLCGDDTMRLLEKNGLTFPFICKTRVAHGTNSHEMAIVFNQEGLNA
IQPPCVVQNFINHNAVLYKVFVVGESYTVVQRPSLKNFSAGTSDRESIFFNSHNVSKPES
SSVLTELDKIEGVFERPSDEVIRELSRALRQALGVSLFGIDIIINNQTGQHAVIDINAFP
GYEGVSEFFTDLLNHIATVLQGQSTAMAATGDVALLRHSKLLAEPAGGLVGERTCSASPG
CCGSMMGQDAPWKAEADAGGTAKLPHQRLGCNAGVSPSFQQHCVASLATKASSQ
GenBank ID Protein 12006346
UniProtKB/Swiss-Prot ID Q13572
UniProtKB/Swiss-Prot Entry Name ITPK1_HUMAN
PDB IDs
GenBank Gene ID AF279372
GeneCard ID ITPK1
GenAtlas ID ITPK1
HGNC ID HGNC:6177
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Wilson MP, Majerus PW: Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme. J Biol Chem. 1996 May 17;271(20):11904-10. [PubMed:8662638 ]
  3. Yang X, Shears SB: 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. 2000 Nov 1;351 Pt 3:551-5. [PubMed:11042108 ]
  4. Wilson MP, Sun Y, Cao L, Majerus PW: 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. 2001 Nov 2;276(44):40998-1004. Epub 2001 Aug 31. [PubMed:11533064 ]
  5. Ho MW, Yang X, Carew MA, Zhang T, Hua L, Kwon YU, Chung SK, Adelt S, Vogel G, Riley AM, Potter BV, Shears SB: Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase. Curr Biol. 2002 Mar 19;12(6):477-82. [PubMed:11909533 ]
  6. Sun Y, Wilson MP, Majerus PW: Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1. J Biol Chem. 2002 Nov 29;277(48):45759-64. Epub 2002 Sep 24. [PubMed:12324474 ]
  7. Sun Y, Mochizuki Y, Majerus PW: Inositol 1,3,4-trisphosphate 5/6-kinase inhibits tumor necrosis factor-induced apoptosis. J Biol Chem. 2003 Oct 31;278(44):43645-53. Epub 2003 Aug 18. [PubMed:12925536 ]
  8. Qian X, Mitchell J, Wei SJ, Williams J, Petrovich RM, Shears SB: The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein kinase. Biochem J. 2005 Jul 15;389(Pt 2):389-95. [PubMed:15762844 ]
  9. Miller GJ, Wilson MP, Majerus PW, Hurley JH: Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase. Mol Cell. 2005 Apr 15;18(2):201-12. [PubMed:15837423 ]
  10. Chamberlain PP, Qian X, Stiles AR, Cho J, Jones DH, Lesley SA, Grabau EA, Shears SB, Spraggon G: Integration of inositol phosphate signaling pathways via human ITPK1. J Biol Chem. 2007 Sep 21;282(38):28117-25. Epub 2007 Jul 6. [PubMed:17616525 ]