PROSITE documentation PDOC00710
Phosphatidylinositol 3- and 4-kinases catalytic domain signatures and profile


Phosphatidylinositol 3-kinase (PI3-kinase) (EC [1] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The exact function of the three products of PI3-kinase - PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3) - is not yet known, although it is proposed that they function as second messengers in cell signalling. Currently, three forms of PI3-kinase are known:

  • The mammalian enzyme which is a heterodimer of a 110 Kd catalytic chain (p110) and an 85 Kd subunit (p85) which allows it to bind to activated tyrosine protein kinases. There are at least two different types of p100 subunits (α and β).
  • Yeast TOR1/DRR1 and TOR2/DRR2 [2], PI3-kinases required for cell cycle activation. Both are proteins of about 280 Kd.
  • Yeast VPS34 [3], a PI3-kinase involved in vacuolar sorting and segregation. VPS34 is a protein of about 100 Kd.
  • Arabidopsis thaliana and soybean VPS34 homologs.

Phosphatidylinositol 4-kinase (PI4-kinase) (EC [4] is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate. Currently the following forms of PI4-kinases are known:

  • Human PI4-kinase α.
  • Yeast PIK1, a nuclear protein of 120 Kd.
  • Yeast STT4, a protein of 214 Kd.

The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain of protein kinases [2]. The PI3K/PI4K catalytic domain is divided into an N-lobe and a C-lobe (see <PDB:4HNE>). The N-lobe contains a five-stranded $antiparallel β-sheet core flanked by a helical hairpin on one side and a helix on the other. The C-lobe contains helices, which form a helical bundle together with the N-lobe helix. The helical bundle is flanked by three β-strands and a helix. Three loops are related to kinase activity, the glycine-rich G-loop, the catalytic loop and the activation loop. The G-loop has been reported to bind to the phosphate group of nucleotides [5].

Four additional proteins belong to this family:

  • Mammalian FKBP-rapamycin associated protein (FRAP) [6], which acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex.
  • Yeast protein ESR1 [7] which is required for cell growth, DNA repair and meiotic recombination.
  • Yeast protein TEL1 which is involved in controlling telomere length.
  • Yeast hypothetical protein YHR099w, a distantly related member of this family.
  • Fission yeast hypothetical protein SpAC22E12.16C.

We developed two signature patterns from the best conserved parts of the C-terminal domain. A profile was also developed that spans the complete domain.

Last update:

October 2021 / Profile and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

PI3_4_KINASE_3, PS50290; Phosphatidylinositol 3- and 4-kinases catalytic domain profile  (MATRIX)

PI3_4_KINASE_1, PS00915; Phosphatidylinositol 3- and 4-kinases signature 1  (PATTERN)

PI3_4_KINASE_2, PS00916; Phosphatidylinositol 3- and 4-kinases signature 2  (PATTERN)


1AuthorsHiles I.D. Otsu M. Volinia S. Fry M.J. Gout I. Dhand R. Panayotou G. Ruiz-Larrea F. Thompson A. Totty N.F.
TitlePhosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit.
SourceCell 70:419-429(1992).
PubMed ID1322797

2AuthorsKunz J. Henriquez R. Schneider U. Deuter-Reinhard M. Movva N.R. Hall M.N.
TitleTarget of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression.
SourceCell 73:585-596(1993).
PubMed ID8387896

3AuthorsSchu P.V. Takegawa K. Fry M.J. Stack J.H. Waterfield M.D. Emr S.D.
TitlePhosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting.
SourceScience 260:88-91(1993).
PubMed ID8385367

4AuthorsGarcia-Bustos J.F. Marini F. Stevenson I. Frei C. Hall M.N.
TitlePIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus.
SourceEMBO. J. 13:2352-2361(1994).
PubMed ID8194527

5AuthorsZhou Q. Li J. Yu H. Zhai Y. Gao Z. Liu Y. Pang X. Zhang L. Schulten K. Sun F. Chen C.
TitleMolecular insights into the membrane-associated phosphatidylinositol 4-kinase IIalpha.
SourceNat. Commun. 5:3552-3552(2014).
PubMed ID24675427

6AuthorsBrown E.J. Albers M.W. Shin T.B. Ichikawa K. Keith C.T. Lane W.S. Schreiber S.L.
TitleA mammalian protein targeted by G1-arresting rapamycin-receptor complex.
SourceNature 369:756-758(1994).
PubMed ID8008069

7AuthorsKato R. Ogawa H.
TitleAn essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae.
SourceNucleic Acids Res. 22:3104-3112(1994).
PubMed ID8065923

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