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Homo sapiens Protein: PAS complex

Subunit composition of PAS complex = [PIKFYVE][FIG4][VAC14]
         FYVE finger-containing phosphoinositide kinase = PIKFYVE (summary available)
         phosphatidylinositol 3,5-bisphosphate 5-phosphatase = FIG4

Summary:
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-Reaction Schematic: ?

Credits:
Created 13-Oct-2009 by Caspi R , SRI International


Component enzyme of PAS complex : FYVE finger-containing phosphoinositide kinase

Gene: PIKFYVE Accession Number: HS03825 (HumanCyc)

Unification Links: MOPED:Q9Y2I7 , UniProt:Q9Y2I7

Catalyzes:
a 1-phosphatidyl-1D-myo-inositol 3-phosphate + ATP → 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + ADP + H+

Summary:
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].

Mutations in the PIKFYVE gene are associated with François-Neetens mouchetée fleck corneal dystrophy [Li05].


Component enzyme of PAS complex : phosphatidylinositol 3,5-bisphosphate 5-phosphatase

Synonyms: Sac domain-containing inositol phosphatase 3, Sac3

Gene: FIG4 Accession Number: HS12771 (HumanCyc)

Gene Class: UNCLASSIFIED

Unification Links: MOPED:Q92562 , UniProt:Q92562

Catalyzes:
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

Citations: [Minagawa01, Nagase96]


Subunit of PAS complex: Vac14

Synonyms: FLJ10305, ArPIKfyve

Gene: VAC14 Accession Number: HS02446 (HumanCyc)

Unification Links: MOPED:Q08AM6 , UniProt:Q08AM6


References

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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Please cite the following article in publications resulting from the use of HumanCyc: Genome Biology 6(1):1-17 2004
Page generated by SRI International Pathway Tools version 18.0 on Wed Sep 17, 2014, BIOCYC11A.