The PAS regulatory complex regulates both the synthesis and turnover of phosphatidylinositol-3,5-bisphosphate. The kinase and phosphatase both interact with the VAC14 protein, which acts as a scaffold [Sbrissa08].
|Gene:||PIKFYVE||Accession Number: HS03825 (HumanCyc)|
Phosphatidylinositol-3,5 bisphosphosphate is vital in the differentiation and development of multicellular organisms. This compound is synthesized from a 1-phosphatidyl-1D-myo-inositol 3-phosphate only by the very large enzyme, FYVE finger-containing phosphoinositide kinase. A knockout of this enzyme or its associated regulator Vac14 is lethal [Zhang07a].
In addition to a C-terminally positioned catalytic domain, this protein harbors a FYVE finger domain, which is essential for targeting the protein to phosphatidyl-inositol 3-phosphate located within intracellular membranes [Sbrissa02].
The protein forms a complex with the regulator Vac14 (ArPIKfyve) and the phosphatidylinositol 3,5-bisphosphate 5-phosphatase (Sac3 or FIG4) [Sbrissa07, Sbrissa08].
Synonyms: Sac domain-containing inositol phosphatase 3, Sac3
|Gene:||FIG4||Accession Number: HS12771 (HumanCyc)|
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O → a 1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate ,
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O → a 1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate
Synonyms: FLJ10305, ArPIKfyve
|Gene:||VAC14||Accession Number: HS02446 (HumanCyc)|
Li05: Li S, Tiab L, Jiao X, Munier FL, Zografos L, Frueh BE, Sergeev Y, Smith J, Rubin B, Meallet MA, Forster RK, Hejtmancik JF, Schorderet DF (2005). "Mutations in PIP5K3 are associated with Francois-Neetens mouchetee fleck corneal dystrophy." Am J Hum Genet 77(1);54-63. PMID: 15902656
Minagawa01: Minagawa T, Ijuin T, Mochizuki Y, Takenawa T (2001). "Identification and characterization of a sac domain-containing phosphoinositide 5-phosphatase." J Biol Chem 276(25);22011-5. PMID: 11274189
Nagase96: Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (1996). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." DNA Res 3(5);321-9, 341-54. PMID: 9039502
Sbrissa02: Sbrissa D, Ikonomov OC, Shisheva A (2002). "Phosphatidylinositol 3-phosphate-interacting domains in PIKfyve. Binding specificity and role in PIKfyve. Endomenbrane localization." J Biol Chem 277(8);6073-9. PMID: 11706043
Sbrissa07: Sbrissa D, Ikonomov OC, Fu Z, Ijuin T, Gruenberg J, Takenawa T, Shisheva A (2007). "Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex." J Biol Chem 282(33);23878-91. PMID: 17556371
Sbrissa08: Sbrissa D, Ikonomov OC, Fenner H, Shisheva A (2008). "ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality." J Mol Biol 384(4);766-79. PMID: 18950639
Zhang07a: Zhang Y, Zolov SN, Chow CY, Slutsky SG, Richardson SC, Piper RC, Yang B, Nau JJ, Westrick RJ, Morrison SJ, Meisler MH, Weisman LS (2007). "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice." Proc Natl Acad Sci U S A 104(44);17518-23. PMID: 17956977
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