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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:47 UTC
HMDB IDHMDB01059
Secondary Accession NumbersNone
Metabolite Identification
Common NameInositol 1,3,4,5-tetraphosphate
DescriptionInositol 1,3,4,5-tetrakisphopsphate (IP4) is a second messenger responsible for mediating Ca2+ entry through plasma membrane and mobilize intracellular Ca2+ by acting synergistically with inositol 1,4,5-trisphosphate (IP3). Inositol 1,4,5-trisphosphate 3-kinase (IP3K, EC 2.7.1.127) phosphorylates IP3 to IP4. Evidence shows that IP4 can activate a protein with ras- and rap-GAP activity and finally inactivate the G protein. This indicates that IP4 regulates Ca2+ influx in a GTP-dependent way, which potentially links the IP3 signaling pathway to GTP-regulated signaling mechanisms. IP4 is demonstrated to be a common regulator in Ca2+ homeostasis. IP4 can bind with high affinity to several intracellular proteins: synaptotagmin (I and II), Gap1, Btk, and centaurin-alpha-and may interact with synaptotagmin to inhibit synaptic transmission. IP4 also acts as a mediator in neuronal death in the ischemic hippocampus. IP4 production is not always associated with modification in calcium concentration, and control of calcium mobilization is not the sole function proposed for IP4. IP4 define an essential signaling pathway for T cell precursor responsiveness and development. In the thymus, IP4 is essential during positive and negative selection of double-positive thymocytes, and in the control of thymocyte reactivity to antigens. 1D-Myo-inositol 1,3,4,5-tetrakisphosphate is also a substrate for Type I inositol-1,4,5-trisphosphate 5-phosphatase, Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A and Skeletal muscle and kidney enriched inositol phosphatase. (PMID: 15740635 , 14517551 ).
Structure
Thumb
Synonyms
ValueSource
1,3,4,5-Tetrakis(dihydrogen phosphate) myo-inositolHMDB
1D-myo-Inositol 1,3,4,5-tetrakis(dihydrogen phosphate)HMDB
1D-myo-Inositol 1,3,4,5-tetrakisphosphateHMDB
D-myo-Inositol 1,3,4,5-tetrakisphosphateHMDB
Inositol 1,3,4,5-tetrakis(phosphate)HMDB
Inositol 1,3,4,5-tetrakisphosphateHMDB
Inositol-(1,3,4,5)-tetrakisphosphateHMDB
Inositol-1,3,4,5-tetrakisphosphateHMDB
Inositol-1,3,4,5-tetraphosphateHMDB
Ins-1,3,4,5-P4HMDB
myo-Inositol 1,3,4,5-tetrakis(phosphate)HMDB
myo-Inositol 1,3,4,5-tetraphosphateHMDB
myo-Inositol, 1,3,4,5-tetrakis(dihydrogen phosphate)HMDB
myo-Inositol-1,3,4,5-tetrakisphosphateHMDB
[(2R,3S,5S,6S)-3,5-Dihydroxy-2,4,6-triphosphonooxycyclohexyl] dihydrogen phosphateHMDB
Chemical FormulaC6H16O18P4
Average Molecular Weight500.0755
Monoisotopic Molecular Weight499.928709756
IUPAC Name{[(2S,3R,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxy}phosphonic acid
Traditional Name[(2S,3R,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxyphosphonic acid
CAS Registry Number102850-29-3
SMILES
O[C@H]1C(OP(O)(O)=O)[C@H](O)[C@@H](OP(O)(O)=O)C(OP(O)(O)=O)[C@H]1OP(O)(O)=O
InChI Identifier
InChI=1S/C6H16O18P4/c7-1-3(21-25(9,10)11)2(8)5(23-27(15,16)17)6(24-28(18,19)20)4(1)22-26(12,13)14/h1-8H,(H2,9,10,11)(H2,12,13,14)(H2,15,16,17)(H2,18,19,20)/t1-,2-,3?,4-,5+,6?/m0/s1
InChI KeyInChIKey=CIPFCGZLFXVXBG-FTSGZOCFSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as inositol phosphates. These are compounds containing a phosphate group attached to an inositol (or cyclohexanehexol) moiety.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassAlcohols and polyols
Sub ClassCyclic alcohols and derivatives
Direct ParentInositol phosphates
Alternative Parents
Substituents
  • Inositol phosphate
  • Monoalkyl phosphate
  • Cyclohexanol
  • Alkyl phosphate
  • Phosphoric acid ester
  • Organic phosphoric acid derivative
  • Organic phosphate
  • Secondary alcohol
  • Hydrocarbon derivative
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
Biofunction
  • Component of Inositol phosphate metabolism
  • Second messenger
Application
  • .
Cellular locations
  • Nucleus
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility11.5 mg/mLALOGPS
logP-0.45ALOGPS
logP-4.3ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)0.33ChemAxon
Physiological Charge-8ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area307.5 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity79.27 m3·mol-1ChemAxon
Polarizability34.13 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Nucleus
Biofluid LocationsNot Available
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Inositol MetabolismSMP00011map00562
Inositol Phosphate MetabolismSMP00462map00562
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022398
KNApSAcK IDNot Available
Chemspider ID96919
KEGG Compound IDC01272
BioCyc IDCPD-506
BiGG ID37244
Wikipedia Link.
NuGOwiki LinkHMDB01059
Metagene LinkHMDB01059
METLIN ID5973
PubChem Compound107758
PDB ID1B55
ChEBI ID16783
References
Synthesis ReferenceDeSolms, S. Jane; Vacca, Joseph P.; Huff, Joel R. The total synthesis of (±)-myo-inositol-1,3,4-triphosphate, (±)-myo-inositol-2,4,5-triphosphate and (±)-myo-inositol-1,3,4,5-tetraphosphate. Tetrahedron Letters (1987), 28(39), 4503-6.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Han SY, Kato H, Kato S, Suzuki T, Shibata H, Ishii S, Shiiba K, Matsuno S, Kanamaru R, Ishioka C: Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay. Cancer Res. 2000 Jun 15;60(12):3147-51. [10866302 ]
  2. Cozier GE, Lockyer PJ, Reynolds JS, Kupzig S, Bottomley JR, Millard TH, Banting G, Cullen PJ: GAP1IP4BP contains a novel group I pleckstrin homology domain that directs constitutive plasma membrane association. J Biol Chem. 2000 Sep 8;275(36):28261-8. [10869341 ]
  3. Horne G, Potter BV: Synthesis of the enantiomers of 6-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate, structural analogues of myo-inositol 1,3,4,5-tetrakisphosphate. Chemistry. 2001 Jan 5;7(1):80-7. [11205029 ]
  4. Xia HJ, Yang G: Inositol 1,4,5-trisphosphate 3-kinases: functions and regulations. Cell Res. 2005 Feb;15(2):83-91. [15740635 ]
  5. Pouillon V, Hascakova-Bartova R, Pajak B, Adam E, Bex F, Dewaste V, Van Lint C, Leo O, Erneux C, Schurmans S: Inositol 1,3,4,5-tetrakisphosphate is essential for T lymphocyte development. Nat Immunol. 2003 Nov;4(11):1136-43. Epub 2003 Sep 28. [14517551 ]

Enzymes

General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Major isoenzyme hydrolyzing the calcium-mobilizing second messenger Ins(1,4,5)P3, this is a signal-terminating reaction.
Gene Name:
INPP5A
Uniprot ID:
Q14642
Molecular weight:
47819.155
Reactions
Inositol 1,3,4,5-tetraphosphate + Water → Inositol 1,3,4-trisphosphate + Phosphoric aciddetails
General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Inositol 5-phosphatase, which converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate. Also converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate in vitro. May be involved in modulation of the function of inositol and phosphatidylinositol polyphosphate-binding proteins that are present at membranes ruffles (By similarity).
Gene Name:
INPP5J
Uniprot ID:
Q15735
Molecular weight:
70238.575
Reactions
Inositol 1,3,4,5-tetraphosphate + Water → Inositol 1,3,4-trisphosphate + Phosphoric aciddetails
General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Has 6-fold higher affinity for phosphatidylinositol 4,5-bisphosphate than for inositol 1,4,5-trisphosphate. May negatively regulate assembly of the actin cytoskeleton.
Gene Name:
INPP5K
Uniprot ID:
Q9BT40
Molecular weight:
42783.425
Reactions
Inositol 1,3,4,5-tetraphosphate + Water → Inositol 1,3,4-trisphosphate + Phosphoric aciddetails
General function:
Involved in inositol trisphosphate 3-kinase activity
Specific function:
Not Available
Gene Name:
ITPKB
Uniprot ID:
P27987
Molecular weight:
102375.325
Reactions
Adenosine triphosphate + Inositol 1,4,5-trisphosphate → ADP + Inositol 1,3,4,5-tetraphosphatedetails
General function:
Involved in inositol trisphosphate 3-kinase activity
Specific function:
Not Available
Gene Name:
ITPKA
Uniprot ID:
P23677
Molecular weight:
51008.32
Reactions
Adenosine triphosphate + Inositol 1,4,5-trisphosphate → ADP + Inositol 1,3,4,5-tetraphosphatedetails
General function:
Involved in inositol trisphosphate 3-kinase activity
Specific function:
Can phosphorylate inositol 2,4,5-triphosphate to inositol 2,4,5,6-tetraphosphate (By similarity).
Gene Name:
ITPKC
Uniprot ID:
Q96DU7
Molecular weight:
75207.0
Reactions
Adenosine triphosphate + Inositol 1,4,5-trisphosphate → ADP + Inositol 1,3,4,5-tetraphosphatedetails
General function:
Involved in inositol or phosphatidylinositol phosphatase activity
Specific function:
Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.
Gene Name:
INPPL1
Uniprot ID:
O15357
Molecular weight:
138597.495
General function:
Involved in acid phosphatase activity
Specific function:
Acts as a phosphoinositide 5- and phosphoinositide 6-phosphatase and regulates cellular levels of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Also acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to produce phospho-D-glycerate without formation of 3-phosphoglycerate. May play a role in bone development (endochondral ossification).
Gene Name:
MINPP1
Uniprot ID:
Q9UNW1
Molecular weight:
34660.555
Reactions
Inositol 1,3,4,5-tetraphosphate + Water → Inositol 1,4,5-trisphosphate + Phosphoric aciddetails
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.
Gene Name:
ITPK1
Uniprot ID:
Q13572
Molecular weight:
45620.645
Reactions
Adenosine triphosphate + Inositol 1,3,4-trisphosphate → ADP + Inositol 1,3,4,5-tetraphosphatedetails