The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  19 GLDLSVPQHQEVRGKMMSGHVEYQILVVTRLAVFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVL 98
Cdd:cd06868     1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907088643  99 FVGESDIRERRAMFDEILRCVSKDAQLAGSPELLEFLGTR 138
Cdd:cd06868    81 FVSESDIRERRAAFNDFMRFISKDEKLANCPELLEFLGVK 120

The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  19 GLDLSVPQHQEVRGKMMSGHVEYQILVVTRLAVFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVL 98
Cdd:cd06868     1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907088643  99 FVGESDIRERRAMFDEILRCVSKDAQLAGSPELLEFLGTR 138
Cdd:cd06868    81 FVSESDIRERRAAFNDFMRFISKDEKLANCPELLEFLGVK 120

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  58 RPEDVVQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVLFVG--ESDIRERRAMFDEILRCVSKDAQLAGSPELLEFL 135
Cdd:pfam00787   2 PTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRynEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  19 GLDLSVPQHQEVRGKMMSGHVEYQILVVTRLAVFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVL 98
Cdd:cd06868     1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907088643  99 FVGESDIRERRAMFDEILRCVSKDAQLAGSPELLEFLGTR 138
Cdd:cd06868    81 FVSESDIRERRAAFNDFMRFISKDEKLANCPELLEFLGVK 120

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643   29 EVRGKMMSGHVEYQILVVTRLavfksakhrpeDVVQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVLFVG-----ES 103
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKT-----------GLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnfsEE 71

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1907088643  104 DIRERRAMFDEILRCVSKDAQLA-GSPELLEFL 135
Cdd:smart00312  72 FIEKRRRGLEKYLQSLLNHPELInHSEVVLEFL 104

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  37 GHVEYQILvvtrlAVFKSaKHRPEDVVQFLVSKKYSEIEEFYQKLysCYPAASL-------PPLPRKVLF--VGESDIRE 107
Cdd:cd07288    16 GYTEYKVT-----AQFIS-KKQPEDVKEVVVWKRYSDLKKLHGEL--AYTHRNLfrrqeefPPFPRAQVFgrFEAAVIEE 87

                          90       100
                  ....*....|....*....|....*...
gi 1907088643 108 RRAMFDEILRCVSKDAQLAGSPELLEFL 135
Cdd:cd07288    88 RRNAAEAMLLFTVNIPALYNSPQLKEFF 115

Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643   2 QSPAVLRTSRQ--VQNAHTGLD------LSVPQHQEVRGKMMSGHVEYQILVVTRLAVFKSAKHRPEdvvqfLVSKKYSE 73
Cdd:COG5391   107 MLSLLLPTSLQppLSTSHTILDyfisstVSNPQSLTLLVDSRDKHTSYEIITVTNLPSFQLRESRPL-----VVRRRYSD 181

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907088643  74 IEEFYQKLYSCYPAASLPPLPRK----VLFVGESD---IRERRAMFDEILRCVSK 121
Cdd:COG5391   182 FESLHSILIKLLPLCAIPPLPSKksnsEYYGDRFSdefIEERRQSLQNFLRRVST 236

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  32 GKMMSGHVEYQILVVTRLAVFKSAkhrpedvvQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVLfVGESD---IRER 108
Cdd:cd06861    12 GDLTSAHTVYTVRTRTTSPNFEVS--------SFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQS-VGRFDdnfVEQR 82

                          90       100
                  ....*....|....*....|....*..
gi 1907088643 109 RAMFDEILRCVSKDAQLAGSPELLEFL 135
Cdd:cd06861    83 RAALEKMLRKIANHPVLQKDPDFRLFL 109

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  56 KHRPEDVVQFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRKvlfvgESDIRER-RAMFDEILRCVSKDAQLAGSPELLEF 134
Cdd:cd06869    41 RREGEEYRTIYVARRYSDFKKLHHDLKKEFPGKKLPKLPHK-----DKLPREKlRLSLRQYLRSLLKDPEVAHSSILQEF 115

                  .
gi 1907088643 135 L 135
Cdd:cd06869   116 L 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX2 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  20 LDLSVPQHQEVrGKMMSGHVEYQILVVTRLAVFksakHRPEdvvqFLVSKKYSEIEEFYQKLYSCYPAASL--PPLPRKV 97
Cdd:cd07282     1 IEIGVSDPEKV-GDGMNAYMAYRVTTKTSLSMF----SRSE----FSVRRRFSDFLGLHSKLASKYLHVGYivPPAPEKS 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907088643  98 LF------VGESD------IRERRAMFDEILRCVSKDAQLAGSPELLEFL 135
Cdd:cd07282    72 IVgmtkvkVGKEDssstefVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  20 LDLSVPQHQEVrGKMMSGHVEYQILVVTRLAVFKSAkhrpedvvQFLVSKKYSEIEEFYQKLYSCYPAAS--LPPLPRKV 97
Cdd:cd07281     1 LKVSITDPEKI-GDGMNAYVVYKVTTQTSLLMFRSK--------HFTVKRRFSDFLGLYEKLSEKHSQNGfiVPPPPEKS 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907088643  98 LF------VGESD------IRERRAMFDEILRCVSKDAQLAGSPELLEFL 135
Cdd:cd07281    72 LIgmtkvkVGKEDsssaefLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907088643  25 PQHQEVRGKmmSGHVEYQILVVTRLAVFKSAKhrpedvvqFLVSKKYSEIEEFYQKLYSCYPAASLPPLPRK 96
Cdd:cd06863     8 PQKELDGSS--DTYISYLITTKTNLPSFSRKE--------FKVRRRYSDFVFLHECLSNDFPACVVPPLPDK 69

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907088643  60 EDVVQFLVSKKYSEIEEFYQKLYSCYPAAS---------LPPLPRKVLFVGESDIRERRAMFDEILRCV-SKDAQLAGSP 129
Cdd:cd06887    28 QDLSEKLVYRRFTEIYEFHKTLKEMFPIEAgdinkenriIPHLPAPKWFDGQRAAENRQGTLTEYCSTLlSLPPKISRCP 107

                  ....*....
gi 1907088643 130 ELLEFLGTR 138
Cdd:cd06887   108 HVLDFFKVR 116

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1907088643  66 LVSKKYSEIEEFYQKLYSCYPAASLPPLPRKVlFVGESDIR---ERR 109
Cdd:cd06883    33 FVFRTFEEFQELHNKLSLLFPSLKLPSFPARV-VLGRSHIKqvaERR 78