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 68800430  19 GLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVL 98
Cdd:cd06868   1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 68800430  99 FVGESDIRERRAVFNEILRCVSKDAELAGSPELLEFLGTR 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 68800430  19 GLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVL 98
Cdd:cd06868   1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 68800430  99 FVGESDIRERRAVFNEILRCVSKDAELAGSPELLEFLGTR 138
Cdd:cd06868  81 FVSESDIRERRAAFNDFMRFISKDEKLANCPELLEFLGVK 120

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430    58 RPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLFVG--ESDIRERRAVFNEILRCVSKDAELAGSPELLEFL 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 68800430  19 GLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVL 98
Cdd:cd06868   1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 68800430  99 FVGESDIRERRAVFNEILRCVSKDAELAGSPELLEFLGTR 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 68800430     29 EVRGKMMSGHVEYQILVVTRLaafksakhrpeDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLFVG-----ES 103
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKT-----------GLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnfsEE 71

                           90       100       110
                   ....*....|....*....|....*....|...
gi 68800430    104 DIRERRAVFNEILRCVSKDAELA-GSPELLEFL 135
Cdd:smart00312  72 FIEKRRRGLEKYLQSLLNHPELInHSEVVLEFL 104

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; 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. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) 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. SNX15 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. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430  37 GHVEYQIlvvtrlaAFKSAKHR-PEDVVQFLVSKKYSEIEEFYQKLSSRYA----AASLPPLPRKVLFvGESD---IRER 108
Cdd:cd06881  16 GYTEYKI-------TSKVFSRSvPEDVSEVVVWKRYSDFKKLHRELSRLHKqlylSGSFPPFPKGKYF-GRFDaavIEER 87

                        90       100
                ....*....|....*....|....*.
gi 68800430 109 RAVFNEILRCVSKDAELAGSPELLEF 134
Cdd:cd06881  88 RQAILELLDFVGNHPALYQSSAFQQF 113

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 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. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor 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. SNX1 and SNX2 are components 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430  32 GKMMSGHVEYQILVVTRLAAFKSAkhrpedvvQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLfVGESD-----IR 106
Cdd:cd06859  12 GDGMSAYVVYRVTTKTNLPDFKKS--------EFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQA-VGRFKvkfefIE 82

                        90       100
                ....*....|....*....|....*....
gi 68800430 107 ERRAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:cd06859  83 KRRAALERFLRRIAAHPVLRKDPDFRLFL 111

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 68800430  32 GKMMSGHVEYQILVVTRLAAFKSAkhrpedvvQFLVSKKYSEIEEFYQKLSSRYAAAS--LPPLPRKVLF------VGES 103
Cdd:cd07281  12 GDGMNAYVVYKVTTQTSLLMFRSK--------HFTVKRRFSDFLGLYEKLSEKHSQNGfiVPPPPEKSLIgmtkvkVGKE 83

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 68800430 104 D------IRERRAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:cd07281  84 DsssaefLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; 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. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430  36 SGHVEYQILVVtrlaafksaKHRPEDVVQFLVSKKYSEIEEFYQKLSSRYaaaslPPL------PRKVLfVG---ESDIR 106
Cdd:cd07279  16 KKYVVYQLAVV---------QTGDPDTQPAFIERRYSDFLKLYKALRKQH-----PQLmakvsfPRKVL-MGnfsSELIA 80

                        90       100
                ....*....|....*....|....*....
gi 68800430 107 ERRAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:cd07279  81 ERSRAFEQFLGHILSIPNLRDSKAFLDFL 109

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430  25 PQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHRPEdvvqfLVSKKYSEIEEFYQKLSSRYAAASLPPLPRK----VLFV 100
Cdd:COG5391 138 PQSLTLLVDSRDKHTSYEIITVTNLPSFQLRESRPL-----VVRRRYSDFESLHSILIKLLPLCAIPPLPSKksnsEYYG 212

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430 101 GESD---IRERRAVFNEILRCVSKDAELAGSPELLEFLGTR----SPGAAGLTSRDSSVLDGTDSQTGNDEEAFDFFEEQ 173
Cdd:COG5391 213 DRFSdefIEERRQSLQNFLRRVSTHPLLSNYKNSKSWESHStllsSFIENRKSVPTPLSLDLTSTTQELDMERKELNEST 292

                ....
gi 68800430 174 DQVA 177
Cdd:COG5391 293 SKAI 296

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 68800430  67 VSKKYSEIEEFYQKLSSRYAAASLPPLPRKVlFVGESDIR---ERR 109
Cdd:cd06884  36 VFRTYKEFLELYQKLCRKFPLAKLHPLSTGS-HVGRSNIKsvaEKR 80

The phosphoinositide binding Phox Homology domain of fungal Grd19; 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. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68800430  32 GKMMsgHVEYQILVVTRLAAFKsakhrpedVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLFVGESD--IRERR 109
Cdd:cd07295  15 GRGM--FTDYEIVCRTNIPAFK--------LRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDevIEERR 84

                        90       100
                ....*....|....*....|....*..
gi 68800430 110 AVFNEILRCVSKDAEL-AGSPELLEFL 135
Cdd:cd07295  85 QGLETFLQSVAGHPLLqTGSKVLAAFL 111

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; 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. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase 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. SNX15 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 68800430  46 VTRLAAFKSAKHRPEDVVQFLVSKKYSEIEEFYQKLSSRYA-----AASLPPLPRKVLF--VGESDIRERRAVFNEILRC 118
Cdd:cd07287  19 VYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKnlcrqSELFPPFAKAKVFgrFDESVIEERRQCAEDLLQF 98

                        90
                ....*....|....*..
gi 68800430 119 VSKDAELAGSPELLEFL 135
Cdd:cd07287  99 SANIPALYNSSQLEDFF 115

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 68800430  66 LVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVlFVGESDIR---ERR 109
Cdd:cd06883  33 FVFRTFEEFQELHNKLSLLFPSLKLPSFPARV-VLGRSHIKqvaERR 78