Inositol monophosphatase 1

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IMPA1
Protein IMPA1 PDB 1awb.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IMPA1, IMP, IMPA, inositol monophosphatase 1
External IDs MGI: 1933158 HomoloGene: 4043 GeneCards: IMPA1
EC number 3.1.3.94
RNA expression pattern
PBB GE IMPA1 203011 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005536
NM_001144878
NM_001144879

NM_018864
NM_001310433

RefSeq (protein)

NP_001138350.1
NP_001138351.1
NP_005527.1

n/a

Location (UCSC) Chr 8: 81.66 – 81.69 Mb Chr 3: 10.31 – 10.33 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Inositol monophosphatase 1 is an enzyme that in humans is encoded by the IMPA1 gene.[3][4]

Interacting partners[edit]

IMPA1 has been shown to interact with Bergmann glial S100B[5] and calbindin.[6][7]

Chemical inhibitors[edit]

L-690,330 is a competitive inhibitor of IMPase activity with very good activity in vitro however with limited bioavailability in vivo.[8] Due to its increased specificity compared to Lithium, L-690,330 has been used extensively in characterizing the results of IMPase inhibition in various cell culture models. L-690,488, a prodrug or L-690,330, has also been developed which has greater cell permeability. Treatment of cortical slices with L-690,488 resulted in accumulation of inositol demonstrating the activity of this inhibitor in tissue.[9]

Inhibition of IMPA1 activity can have pleiotropic effects on cellular function, including altering phosphoinositide signalling,[10] autophagy, apoptosis,[11] and other effects.

Bipolar disorder[edit]

Initially it was noticed that several drugs useful in treatment of biopolar disorder such as lithium, carbamazepine and valproic acid had a common mechanism of action on enzymes in the phosphatidylinositol signalling pathway[12] and the inositol depletion hypothesis for the pathophysiology of biopolar disorder was suggested. Intensive research has so far not confirmed this hypothesis, partly because lithium can also act on a number of other enzymes in this pathway, complicating results from in vitro studies.

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ McAllister G, Whiting P, Hammond EA, Knowles MR, Atack JR, Bailey FJ, Maigetter R, Ragan CI (Aug 1992). "cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme". Biochem J. 284 (3): 749–54. PMC 1132602Freely accessible. PMID 1377913. 
  4. ^ "Entrez Gene: IMPA1 inositol(myo)-1(or 4)-monophosphatase 1". 
  5. ^ Vig PJ, Shao Q, Subramony SH, Lopez ME, Safaya E (September 2009). "Bergmann glial S100B activates myo-inositol monophosphatase 1 and Co-localizes to purkinje cell vacuoles in SCA1 transgenic mice". Cerebellum. 8 (3): 231–44. doi:10.1007/s12311-009-0125-5. PMC 3351107Freely accessible. PMID 19593677. 
  6. ^ Schmidt H, Schwaller B, Eilers J (April 2005). "Calbindin D28k targets myo-inositol monophosphatase in spines and dendrites of cerebellar Purkinje neurons". Proc. Natl. Acad. Sci. U.S.A. 102 (16): 5850–5. doi:10.1073/pnas.0407855102. PMC 556286Freely accessible. PMID 15809430. 
  7. ^ Berggard T, Szczepankiewicz O, Thulin E, Linse S (November 2002). "Myo-inositol monophosphatase is an activated target of calbindin D28k". J. Biol. Chem. 277 (44): 41954–9. doi:10.1074/jbc.M203492200. PMID 12176979. 
  8. ^ Atack JR, Cook SM, Watt AP, Fletcher SR, Ragan CI (February 1993). "In vitro and in vivo inhibition of inositol monophosphatase by the bisphosphonate L-690,330". J. Neurochem. 60 (2): 652–8. doi:10.1111/j.1471-4159.1993.tb03197.x. PMID 8380439. 
  9. ^ Atack JR, Prior AM, Fletcher SR, Quirk K, McKernan R, Ragan CI (July 1994). "Effects of L-690,488, a prodrug of the bisphosphonate inositol monophosphatase inhibitor L-690,330, on phosphatidylinositol cycle markers". J. Pharmacol. Exp. Ther. 270 (1): 70–6. PMID 8035344. 
  10. ^ King JS, Teo R, Ryves J, Reddy JV, Peters O, Orabi B, Hoeller O, Williams RS, Harwood AJ (2009). "The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells". Dis Model Mech. 2 (5-6): 306–12. doi:10.1242/dmm.001271. PMC 2675811Freely accessible. PMID 19383941. 
  11. ^ Sarkar S, Rubinsztein DC (2006). "Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations". Autophagy. 2 (2): 132–4. doi:10.4161/auto.2387. PMID 16874097. 
  12. ^ Williams RS, Cheng L, Mudge AW, Harwood AJ (May 2002). "A common mechanism of action for three mood-stabilizing drugs". Nature. 417 (6886): 292–5. doi:10.1038/417292a. PMID 12015604. 

Further reading[edit]