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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564391110  45 WSDRSVLYLHRSFADLGRLCKRLRDAFP-------EDRSELARAPLRQGLLAIKGAHDietRLNEVEKLLET----VISM 113
Cdd:cd06889   28 WSDGSELFVYRSLEEFRKLHKQLKEKFPveagllrSSDRVLPKFKDAPSLGSLKGSTS---RSLARLKLLETycqeLLRL 104

                         90
                 ....*....|....
gi 564391110 114 PCKYSRSEVVLTFF 127
Cdd:cd06889  105 DEKVSRSPEVIQFF 118

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1, a homolog of the p47phox subunit of phagocytic NADPH oxidase, is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564391110  45 WSDRSVLYLHRSFADLGRLCKRLRDAFP-------EDRSELARAPLRQGLLAIKGAHDietRLNEVEKLLET----VISM 113
Cdd:cd06889   28 WSDGSELFVYRSLEEFRKLHKQLKEKFPveagllrSSDRVLPKFKDAPSLGSLKGSTS---RSLARLKLLETycqeLLRL 104

                         90
                 ....*....|....
gi 564391110 114 PCKYSRSEVVLTFF 127
Cdd:cd06889  105 DEKVSRSPEVIQFF 118

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1, a homolog of the p47phox subunit of phagocytic NADPH oxidase, is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564391110  45 WSDRSVLYLHRSFADLGRLCKRLRDAFP-------EDRSELARAPLRQGLLAIKGAHDietRLNEVEKLLET----VISM 113
Cdd:cd06889   28 WSDGSELFVYRSLEEFRKLHKQLKEKFPveagllrSSDRVLPKFKDAPSLGSLKGSTS---RSLARLKLLETycqeLLRL 104

                         90
                 ....*....|....
gi 564391110 114 PCKYSRSEVVLTFF 127
Cdd:cd06889  105 DEKVSRSPEVIQFF 118

The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p47phox is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity. The PX domain of p47phox is also involved in protein-protein interaction.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564391110  44 EWSDRSVLYLHRSFADLGRLCKRLRDAFP--------EDRSeLARAPLRQGLLAIKGAhdiETRLNEVEKLLETVISMPC 115
Cdd:cd06887   26 KWQDLSEKLVYRRFTEIYEFHKTLKEMFPieagdinkENRI-IPHLPAPKWFDGQRAA---ENRQGTLTEYCSTLLSLPP 101

                         90
                 ....*....|....*.
gi 564391110 116 KYSRSEVVLTFFERSP 131
Cdd:cd06887  102 KISRCPHVLDFFKVRP 117

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; 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. 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. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564391110  46 SDRSVLYLHRSFADLGRLCKRLRDAFPedrseLAR-APLRQGLLAikGAHDI----ETRLNEVEKLLETVISMPCKYSRS 120
Cdd:cd06884   29 NQASPQHVFRTYKEFLELYQKLCRKFP-----LAKlHPLSTGSHV--GRSNIksvaEKRKQDIQQFLNSLFKMAEEVSHS 101

                 ....*..
gi 564391110 121 EVVLTFF 127
Cdd:cd06884  102 DLVYTFF 108