The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1826689220   2 LEVHIPSVGPEAEGPrqspEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVPDFPSKRLPNWRTRGLEQRRQ 81
Cdd:cd06880     1 IEVSIPSYRLEVDES----EKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQ 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1826689220  82 GLETYIQGILYLNQdVPKELLEFLRLRHFPTDSK 115
Cdd:cd06880    77 GLEAYLQGLLKINE-LPKQLLDFLGVRHFPSLPK 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1826689220   2 LEVHIPSVGPEAEGPrqspEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVPDFPSKRLPNWRTRGLEQRRQ 81
Cdd:cd06880     1 IEVSIPSYRLEVDES----EKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQ 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1826689220  82 GLETYIQGILYLNQdVPKELLEFLRLRHFPTDSK 115
Cdd:cd06880    77 GLEAYLQGLLKINE-LPKQLLDFLGVRHFPSLPK 109

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1826689220  30 EVLYSGRRHTVPRRYSEFHALHKRIKKRYK---VPDFPSKRLP-NWRTRGLEQRRQGLETYIQGIL 91
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPsviIPPLPPKRWLgRYNEEFIEKRRKGLEQYLQRLL 66

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1826689220   2 LEVHIPSVGPEAEGPrqspEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVPDFPSKRLPNWRTRGLEQRRQ 81
Cdd:cd06880     1 IEVSIPSYRLEVDES----EKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQ 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1826689220  82 GLETYIQGILYLNQdVPKELLEFLRLRHFPTDSK 115
Cdd:cd06880    77 GLEAYLQGLLKINE-LPKQLLDFLGVRHFPSLPK 109

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 1826689220   2 LEVHIPSVgpeaegprQSPEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVP---DFPSKRLPNWRTRG--- 75
Cdd:cd06897     1 LEISIPTT--------SVSPKPYTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEppyPLPPKSWFLSTSSNpkl 72

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1826689220  76 LEQRRQGLETYIQGILYlNQDVP----KELLEFLRLR 108
Cdd:cd06897    73 VEERRVGLEAFLRALLN-DEDSRwrnsPAVKEFLNLP 108

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. 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. 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 1826689220  16 PRQSPEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKV-----PdfPSKRLPNWRTRGLEQRRQGLETYIQGI 90
Cdd:cd06875     9 PSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVdkdllP--PKKLIGNKSPSFVEKRRKELEIYLQTL 86

                          90       100
                  ....*....|....*....|.
gi 1826689220  91 L-YLNQDVPKELLEFLRLRHF 110
Cdd:cd06875    87 LsFFQKTMPRELAHFLDFHKY 107

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1826689220  39 TVPRRYSEFHALHKRIKKRY---KVPDFPSKR---LPNWRTRGLEQRRQGLETYIQGIL 91
Cdd:cd06876    58 VVARRYSEFLELHKYLKKRYpgvLKLDFPQKRkisLKYSKTLLVEERRKALEKYLQELL 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1826689220  42 RRYSEFHALHKRIKKRY----KVPdFPSKR-LPNWRTRGLEQRRQGLETYIQGIL 91
Cdd:cd06873    45 RRYSDFHDLHMRLKEKFpnlsKLS-FPGKKtFNNLDRAFLEKRRKMLNQYLQSLL 98

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; 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. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1826689220  24 HMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYK---VPDFPSKRL-PNWRTRGLEQRRQGLETYIQ 88
Cdd:cd06874    18 HFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKYPevaALEFPPKKLfGNKSERVAKERRRQLETYLR 86

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; 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. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1826689220  37 RHTVPRRYSEFHALHKRIKKR---YKVPDFPSKRLPNWRTRGLEQRRQGLETYIQ 88
Cdd:cd06886    31 RQLCSRRYREFANLHQNLKKEfpdFQFPKLPGKWPFSLSEQQLDARRRGLEQYLE 85

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 1826689220  18 QSPEKGHMVFQV--EVLYS-GRRHTVPRRYSEFHALHKRIKKRYK------VPDFPSKR-----LPNWRTRGLEQRRQGL 83
Cdd:cd07280    16 DTGGGAYVVWKItiETKDLiGSSIVAYKRYSEFVQLREALLDEFPrhkrneIPQLPPKVpwydsRVNLNKAWLEKRRRGL 95

                          90       100
                  ....*....|....*....|....*
gi 1826689220  84 ETYIQGILyLNQDV--PKELLEFLR 106
Cdd:cd07280    96 QYFLNCVL-LNPVFggSPVVKEFLL 119

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1826689220  20 PEKGHMVFQ-VEVLYSGRRH--TVPRRYSEFHALHKRIKKRY---KVPDFPSKRLPNWRTRG-LEQRRQGLETYI 87
Cdd:cd06866     9 PEKKGLFLKhVEYEVSSKRFksTVYRRYSDFVWLHEYLLKRYpyrMVPALPPKRIGGSADREfLEARRRGLSRFL 83

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; 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. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1826689220  39 TVPRRYSEFHALHKRIK------KRYKVPDFPSKRLPNWRTRGLEQRRQGLETYIQGIL---YLNQDvpKELLEFL 105
Cdd:cd06878    51 VVTRKLSEFHDLHRKLKecsswlKKVELPSLSKKWFKSIDKKFLDKSKNQLQKYLQFILedeTLCQS--EALYSFL 124

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 1826689220  17 RQSPEKGHMvFQVEVLYSGRRHT--VPRRYSEFHALHKRIKKRYkvPDFPSKRLPNW----RTRGL---EQRRQGLETYI 87
Cdd:cd06883    10 RYSPEKYYI-YVVKVTRENQTEPsfVFRTFEEFQELHNKLSLLF--PSLKLPSFPARvvlgRSHIKqvaERRKIELNSYL 86

                          90
                  ....*....|
gi 1826689220  88 QGILYLNQDV 97
Cdd:cd06883    87 KSLFNASPEV 96

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1826689220  24 HMVFQVEV-LYSGRRHTVPRRYSEFHALHKRIKKRY-----------KVPDFPSKRLPNWRTRGLEQRRQGLETYIQGIL 91
Cdd:cd06882    20 YYVFVIEVkTKGGSKYLIYRRYRQFFALQSKLEERFgpeagssaydcTLPTLPGKIYVGRKAEIAERRIPLLNRYMKELL 99

                          90       100
                  ....*....|....*....|...
gi 1826689220  92 YLNQDVPKELLEFLRLRHFPTDS 114
Cdd:cd06882   100 SLPVWVLMDEDVRLFFYQTESDS 122

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; 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. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1826689220  38 HTVPRRYSEFHALHKRIKKRYKVPDF-----PSKRLP-----NWRTRGLEQRRQGLETYIQGIL-YLNQDVPKELLEFLR 106
Cdd:cd06893    51 HTVNRRFREFLTLQTRLEENPKFRKImnvkgPPKRLFdlpfgNMDKDKIEARRGLLETFLRQLCsIPEISNSEEVQEFLA 130

                  .
gi 1826689220 107 L 107
Cdd:cd06893   131 Y 131

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1826689220  26 VFQVEVLYSGRRH-TVPRRYSEFHALHKRIKKRYkvPDF----PSKRL--PNWRTRGLEQRRQGLETYIQGIL 91
Cdd:cd07276    22 VYKIRVENKVGDSwFVFRRYTDFVRLNDKLKQMF--PGFrlslPPKRWfkDNFDPDFLEERQLGLQAFVNNIM 92

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. 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. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1826689220  24 HMVFQVEVLYSG----RRHTVPRRYSEFHALHKRIKK--RYKVPD--FPSKRLP-NWRTRGLEQRRQGLETYIqGILYLN 94
Cdd:cd07300    18 HVVYQIIVIQTGsfdcNKVVIERRYSDFLKLHQELLSdfSEELEDvvFPKKKLTgNFSEEIIAERRVALRDYL-TLLYSL 96

                          90
                  ....*....|...
gi 1826689220  95 QDV--PKELLEFL 105
Cdd:cd07300    97 RFVrrSQAFQDFL 109

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 1826689220  11 PEAEGPRQSPEKGHMVFQVEVL-----YSGRRH--------TVPRRYSEFHALHKRIKKRYK---VPDFPSKRLpnWRTR 74
Cdd:cd06868     7 PEYQEIRGKTSSGHVLYQIVVVtrlaaFKSAKHkeedvvqfMVSKKYSEFEELYKKLSEKYPgtiLPPLPRKAL--FVSE 84

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1826689220  75 G-LEQRRQGLETYIQGIlylNQDvPK-----ELLEFL 105
Cdd:cd06868    85 SdIRERRAAFNDFMRFI---SKD-EKlancpELLEFL 117