The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958672231 356 GVQRR-RADKYWEYTFKVNWSDLSVTT-VTKTHQELQEFLLKLPKEFSS---ESFDKTILKALNQGSlRREERRHPDLEP 430
Cdd:cd06883     6 GFQKRySPEKYYIYVVKVTRENQTEPSfVFRTFEEFQELHNKLSLLFPSlklPSFPARVVLGRSHIK-QVAERRKIELNS 84

                          90       100
                  ....*....|....*....|....*.
gi 1958672231 431 ILRQLFSTSPQAfLQSHKVRSFFRSI 456
Cdd:cd06883    85 YLKSLFNASPEV-AESDLVYTFFHPL 109

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958672231 356 GVQRR-RADKYWEYTFKVNWSDLSVTT-VTKTHQELQEFLLKLPKEFSS---ESFDKTILKALNQGSlRREERRHPDLEP 430
Cdd:cd06883     6 GFQKRySPEKYYIYVVKVTRENQTEPSfVFRTFEEFQELHNKLSLLFPSlklPSFPARVVLGRSHIK-QVAERRKIELNS 84

                          90       100
                  ....*....|....*....|....*.
gi 1958672231 431 ILRQLFSTSPQAfLQSHKVRSFFRSI 456
Cdd:cd06883    85 YLKSLFNASPEV-AESDLVYTFFHPL 109

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958672231 356 GVQRR-RADKYWEYTFKVNWSDLSVTT-VTKTHQELQEFLLKLPKEFSS---ESFDKTILKALNQGSlRREERRHPDLEP 430
Cdd:cd06883     6 GFQKRySPEKYYIYVVKVTRENQTEPSfVFRTFEEFQELHNKLSLLFPSlklPSFPARVVLGRSHIK-QVAERRKIELNS 84

                          90       100
                  ....*....|....*....|....*.
gi 1958672231 431 ILRQLFSTSPQAfLQSHKVRSFFRSI 456
Cdd:cd06883    85 YLKSLFNASPEV-AESDLVYTFFHPL 109