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 1984025264  19 GLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHKPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVL 98
Cdd:cd06868     1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1984025264  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 1984025264  19 GLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHKPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVL 98
Cdd:cd06868     1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1984025264  99 FVGESDIRERRAVFNEILRCVSKDAELAGSPELLEFLGTR 138
Cdd:cd06868    81 FVSESDIRERRAAFNDFMRFISKDEKLANCPELLEFLGVK 120

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1984025264  65 FLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLFVG--ESDIRERRAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:pfam00787   9 WSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRynEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 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 1984025264  19 GLDLTVPQHQEVRGKMMSGHVEYQILVVTRLAAFKSAKHKPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVL 98
Cdd:cd06868     1 GLDLTVPEYQEIRGKTSSGHVLYQIVVVTRLAAFKSAKHKEEDVVQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1984025264  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 1984025264   29 EVRGKMMSGHVEYQILVVTRLaafksakhkpeDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLFVG-----ES 103
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKT-----------GLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRlnnfsEE 71

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1984025264  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 1984025264  37 GHVEYQIlvvtrlaAFKSAKHK-PEDVVQFLVSKKYSEIEEFYQKLSSRYA----AASLPPLPRKVLFvGESD---IRER 108
Cdd:cd06881    16 GYTEYKI-------TSKVFSRSvPEDVSEVVVWKRYSDFKKLHRELSRLHKqlylSGSFPPFPKGKYF-GRFDaavIEER 87

                          90       100
                  ....*....|....*....|....*.
gi 1984025264 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 1984025264  32 GKMMSGHVEYQILVVTRLAAFKSAkhkpedvvQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLfVGESD-----IR 106
Cdd:cd06859    12 GDGMSAYVVYRVTTKTNLPDFKKS--------EFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQA-VGRFKvkfefIE 82

                          90       100
                  ....*....|....*....|....*....
gi 1984025264 107 ERRAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:cd06859    83 KRRAALERFLRRIAAHPVLRKDPDFRLFL 111

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 1984025264  56 KHKPEDVVQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKvlfvgESDIRER-RAVFNEILRCVSKDAELAGSPELLEF 134
Cdd:cd06869    41 RREGEEYRTIYVARRYSDFKKLHHDLKKEFPGKKLPKLPHK-----DKLPREKlRLSLRQYLRSLLKDPEVAHSSILQEF 115

                  .
gi 1984025264 135 L 135
Cdd:cd06869   116 L 116

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 1984025264  32 GKMMSGHVEYQILVVTRLAAFKSAkhkpedvvQFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLfVGESD---IRER 108
Cdd:cd06861    12 GDLTSAHTVYTVRTRTTSPNFEVS--------SFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQS-VGRFDdnfVEQR 82

                          90       100
                  ....*....|....*....|....*..
gi 1984025264 109 RAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:cd06861    83 RAALEKMLRKIANHPVLQKDPDFRLFL 109

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; 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. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. 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 YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1984025264  21 DLTVPQHQEVRGKMMSG-HVEYQILVVTrlaafksakhKPEDVVQFLVSKKYSEIEEFYQKLSSRY---AAASLPPLPRK 96
Cdd:cd07280     4 DVNVGDYTIVGGDTGGGaYVVWKITIET----------KDLIGSSIVAYKRYSEFVQLREALLDEFprhKRNEIPQLPPK 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1984025264  97 VLFVgESDIR-------ERRAVFNEILRCVSKDAELAGSPELLEFLGT 137
Cdd:cd07280    74 VPWY-DSRVNlnkawleKRRRGLQYFLNCVLLNPVFGGSPVVKEFLLP 120

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 1984025264  67 VSKKYSEIEEFYQKLSSRYAAASLPPLPRKVlFVGESDIR---ERR 109
Cdd:cd06884    36 VFRTYKEFLELYQKLCRKFPLAKLHPLSTGS-HVGRSNIKsvaEKR 80

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; 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. This subfamily is composed of fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1984025264  20 LDLTVPQHQEVRgkmmSGHVEYQILVVTRLAAFKsakhkpedvvqflVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLF 99
Cdd:cd06897     1 LEISIPTTSVSP----KPYTVYNIQVRLPLRSYT-------------VSRRYSEFVALHKQLESEVGIEPPYPLPPKSWF 63

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1984025264 100 VGESD----IRERRAVFNEILRCV--SKDAELAGSPELLEFLG 136
Cdd:cd06897    64 LSTSSnpklVEERRVGLEAFLRALlnDEDSRWRNSPAVKEFLN 106

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1984025264  25 PQHQEVRGKmmSGHVEYQILVVTRLAAFKSAKhkpedvvqFLVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVLF----- 99
Cdd:cd06863     8 PQKELDGSS--DTYISYLITTKTNLPSFSRKE--------FKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLeyitg 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1984025264 100 --VGESDIRERRAVFNEILRCVSKDAELAGSPELLEFL 135
Cdd:cd06863    78 drFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 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 1984025264  66 LVSKKYSEIEEFYQKLSSRYAAASLPPLPRKVlFVGESDIR---ERR 109
Cdd:cd06883    33 FVFRTFEEFQELHNKLSLLFPSLKLPSFPARV-VLGRSHIKqvaERR 78