Phosphatidylinositol-4,5-bisphosphate 3-kinase

Thus, the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, whereas its two products are ADP and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.

This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase. This enzyme is also called type I phosphoinositide 3-kinase. This enzyme participates in 29 metabolic pathways: inositol phosphate metabolism, erbb signaling pathway, phosphatidylinositol signaling system, mtor signaling pathway, apoptosis, VEGF signaling pathway, focal adhesion, toll-like receptor signaling pathway, jak-stat signaling pathway, natural killer cell mediated cytotoxicity, t cell receptor signaling pathway, b cell receptor signaling pathway, fc epsilon ri signaling pathway, leukocyte transendothelial migration, regulation of actin cytoskeleton, insulin signaling pathway, progesterone-mediated oocyte maturation, Type II diabetes mellitus, colorectal cancer, renal cell carcinoma, pancreatic cancer, endometrial cancer, glioma, prostate cancer, melanoma, chronic myeloid leukemia, acute myeloid leukemia, small cell lung cancer, and non-small cell lung cancer.

Structural studies

As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes 2A4Z, 2A5U, 2CHW, 2CHX, 2CHZ, and 2V1Y.

Examples

Human genes encoding proteins with phosphatidylinositol-4,5-bisphosphate 3-kinase activity include:

References

PC, Woscholski R, Parker PJ, Waterfield MD (2001). "Synthesis and function of 3-phosphorylated inositol lipids". Annu. Rev. Biochem. 70: 535–602. doi:10.1146/annurev.biochem.70.1.535. PMID 11395417.

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO₄)

2.7.1: OH acceptor	Hexo- Gluco- Fructo- Hepatic Galacto- Phosphofructo- 1 Liver Muscle Platelet 2 Riboflavin Shikimate Thymidine ADP-thymidine NAD⁺ Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose-1,6-bisphosphate synthase

2.7.2: COOH acceptor	Phosphoglycerate Aspartate kinase

2.7.3: N acceptor	Creatine

2.7.4: PO₄ acceptor	Phosphomevalonate Adenylate Nucleoside-diphosphate Uridylate Guanylate Thiamine-diphosphate

2.7.6: diphosphotransferase
(P₂O₇)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I II III IV V RNA-directed DNA polymerase Reverse transcriptase Telomerase DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase

RNA nucleotidyltransferase	RNA polymerase/DNA-directed RNA polymerase RNA polymerase I RNA polymerase II RNA polymerase III RNA polymerase IV Primase RNA-dependent RNA polymerase PNPase

Phosphorolytic
3' to 5' exoribonuclease

Nucleotidyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

2.7.8: miscellaneous

Phosphatidyltransferases	CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerol—serine O-phosphatidyltransferase CDP-diacylglycerol—inositol 3-phosphatidyltransferase CDP-diacylglycerol—choline O-phosphatidyltransferase

Glycosyl-1-phosphotransferase	N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO₄; protein acceptor)

2.7.10: protein-tyrosine	see tyrosine kinases

2.7.11: protein-serine/threonine	see serine/threonine-specific protein kinases

2.7.12: protein-dual-specificity	see serine/threonine-specific protein kinases

2.7.13: protein-histidine	Protein-histidine pros-kinase Protein-histidine tele-kinase Histidine kinase

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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