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 564364315   2 LEVHIPSVGPEAEGPrqspEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVPDFPSKRLPNWRTRGLEQRRQ 81
Cdd:cd06880    1 IEVSIPSYRLEVDES----EKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQ 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564364315  82 GLETYIQGVLYLNQdVPKELLEFLRLRHFPTDSKA 116
Cdd:cd06880   77 GLEAYLQGLLKINE-LPKQLLDFLGVRHFPSLPKS 110

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 564364315   2 LEVHIPSVGPEAEGPrqspEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVPDFPSKRLPNWRTRGLEQRRQ 81
Cdd:cd06880    1 IEVSIPSYRLEVDES----EKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQ 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564364315  82 GLETYIQGVLYLNQdVPKELLEFLRLRHFPTDSKA 116
Cdd:cd06880   77 GLEAYLQGLLKINE-LPKQLLDFLGVRHFPSLPKS 110

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564364315   30 EVLYSGRRHTVPRRYSEFHALHKRIKKRYK---VPDFPSKRLP-NWRTRGLEQRRQGLETYIQGVL 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 564364315   2 LEVHIPSVGPEAEGPrqspEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVPDFPSKRLPNWRTRGLEQRRQ 81
Cdd:cd06880    1 IEVSIPSYRLEVDES----EKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSIKTPDFPPKRVRNWNPKVLEQRRQ 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564364315  82 GLETYIQGVLYLNQdVPKELLEFLRLRHFPTDSKA 116
Cdd:cd06880   77 GLEAYLQGLLKINE-LPKQLLDFLGVRHFPSLPKS 110

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 564364315  16 PRQSPEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKV-----PdfPSKRLPNWRTRGLEQRRQGLETYIQGV 90
Cdd:cd06875    9 PSAETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLVAEHKVdkdllP--PKKLIGNKSPSFVEKRRKELEIYLQTL 86

                         90       100
                 ....*....|....*....|.
gi 564364315  91 L-YLNQDVPKELLEFLRLRHF 110
Cdd:cd06875   87 LsFFQKTMPRELAHFLDFHKY 107

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 564364315   2 LEVHIPSVgpeaegprQSPEKGHMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYKVP---DFPSKRLPNWRTRG--- 75
Cdd:cd06897    1 LEISIPTT--------SVSPKPYTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEppyPLPPKSWFLSTSSNpkl 72

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 564364315  76 LEQRRQGLETYIQGvLYLNQDVP----KELLEFLRLR 108
Cdd:cd06897   73 VEERRVGLEAFLRA-LLNDEDSRwrnsPAVKEFLNLP 108

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 564364315  39 TVPRRYSEFHALHKRIKKRY---KVPDFPSKR---LPNWRTRGLEQRRQGLETYIQGVL 91
Cdd:cd06876   58 VVARRYSEFLELHKYLKKRYpgvLKLDFPQKRkisLKYSKTLLVEERRKALEKYLQELL 116

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 564364315  43 RYSEFHALHKRIKKRY---KVPDFPSKRLPNWRTRGLEQRRQGLETYIQGV 90
Cdd:cd06885   34 RYSQLHGLNEQLKKEFgnrKLPPFPPKKLLPLTPAQLEERRLQLEKYLQAV 84

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 564364315  24 HMVFQVEVLYSGRRHTVPRRYSEFHALHKRIKKRYK---VPDFPSKRL-PNWRTRGLEQRRQGLETYIQ 88
Cdd:cd06874   18 HFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKYPevaALEFPPKKLfGNKSERVAKERRRQLETYLR 86

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 564364315  22 KGHMVFQV-----EVLYSGRRHTVPRRYSEFHALHKRIKKRYK---VPDFPSKRL---PNWRTRGLEQRRQGLETYIQGV 90
Cdd:cd06859   16 SAYVVYRVttktnLPDFKKSEFSVLRRYSDFLWLYERLVEKYPgriVPPPPEKQAvgrFKVKFEFIEKRRAALERFLRRI 95

                         90
                 ....*....|....*...
gi 564364315  91 L---YLNQDvpKELLEFL 105
Cdd:cd06859   96 AahpVLRKD--PDFRLFL 111

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 564364315  18 QSPEKGHMVFQV--EVLYS-GRRHTVPRRYSEFHALHKRIKKRYK------VPDFPSKR-----LPNWRTRGLEQRRQGL 83
Cdd:cd07280   16 DTGGGAYVVWKItiETKDLiGSSIVAYKRYSEFVQLREALLDEFPrhkrneIPQLPPKVpwydsRVNLNKAWLEKRRRGL 95

                         90       100
                 ....*....|....*....|....*
gi 564364315  84 ETYIQGVLyLNQDV--PKELLEFLR 106
Cdd:cd07280   96 QYFLNCVL-LNPVFggSPVVKEFLL 119

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 564364315  20 PEKGHMVFQVEVLYSGRRHTVP----RRYSEFHALHKRIKKRYKVP----DFPSKRLP-NWRTRGLEQRRQGLETYIQGV 90
Cdd:cd07279   14 GEKKYVVYQLAVVQTGDPDTQPafieRRYSDFLKLYKALRKQHPQLmakvSFPRKVLMgNFSSELIAERSRAFEQFLGHI 93

                         90
                 ....*....|....*...
gi 564364315  91 LYLNQ-DVPKELLEFLRL 107
Cdd:cd07279   94 LSIPNlRDSKAFLDFLQG 111

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 564364315  39 TVPRRYSEFHALHKRIK------KRYKVPDFPSKRLPNWRTRGLEQRRQGLETYIQGVL---YLNQDvpKELLEFL 105
Cdd:cd06878   51 VVTRKLSEFHDLHRKLKecsswlKKVELPSLSKKWFKSIDKKFLDKSKNQLQKYLQFILedeTLCQS--EALYSFL 124

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
                 ....*....|....*....|....*....|....*....|....*.
gi 564364315  33 YSGRRHTVPRRYSEFHALHKRIKKRY---KVPDFPSK-RLPNWRTR 74
Cdd:cd06869   45 EEYRTIYVARRYSDFKKLHHDLKKEFpgkKLPKLPHKdKLPREKLR 90

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 564364315  24 HMVFQVEV-LYSGRRHTVPRRYSEFHALHKRIKKRY-----------KVPDFPSKRLPNWRTRGLEQRRQGLETYIQGVL 91
Cdd:cd06882   20 YYVFVIEVkTKGGSKYLIYRRYRQFFALQSKLEERFgpeagssaydcTLPTLPGKIYVGRKAEIAERRIPLLNRYMKELL 99

                         90       100
                 ....*....|....*....|...
gi 564364315  92 YLNQDVPKELLEFLRLRHFPTDS 114
Cdd:cd06882  100 SLPVWVLMDEDVRLFFYQTESDS 122

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; 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 is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564364315  36 RRHTVPRRYSEFHALHKRIKKRYK--VPDFPSK----RLPNWRTRGL------EQRRQGLETYIQGV 90
Cdd:cd06894   36 KESSVRRRYSDFEWLRSELERDSKivVPPLPGKalkrQLPFRGDDGIfeeefiEERRKGLETFINKV 102

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 564364315  38 HTVPRRYSEFHALHKRIKKRYKVPDF-----PSKRLP-----NWRTRGLEQRRQGLETYIqGVLYLNQDV--PKELLEFL 105
Cdd:cd06893   51 HTVNRRFREFLTLQTRLEENPKFRKImnvkgPPKRLFdlpfgNMDKDKIEARRGLLETFL-RQLCSIPEIsnSEEVQEFL 129

                 ..
gi 564364315 106 RL 107
Cdd:cd06893  130 AY 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 564364315  26 VFQVEVLYSGRRH-TVPRRYSEFHALHKRIKKRYkvPDF----PSKRL--PNWRTRGLEQRRQGLETYIQGVL 91
Cdd:cd07276   22 VYKIRVENKVGDSwFVFRRYTDFVRLNDKLKQMF--PGFrlslPPKRWfkDNFDPDFLEERQLGLQAFVNNIM 92

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 564364315  11 PEAEGPRQSPEKGHMVFQVEVL-----YSGRRH--------TVPRRYSEFHALHKRIKKRYK---VPDFPSKRLpnWRTR 74
Cdd:cd06868    7 PEYQEIRGKTSSGHVLYQIVVVtrlaaFKSAKHkeedvvqfMVSKKYSEFEELYKKLSEKYPgtiLPPLPRKAL--FVSE 84

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 564364315  75 G-LEQRRQGLETYIQGVlylNQDvPK-----ELLEFL 105
Cdd:cd06868   85 SdIRERRAAFNDFMRFI---SKD-EKlancpELLEFL 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; 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. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564364315   4 VHIPSVGPeaegpRQSPEKGH--MVFQVEVLYSGRRH--------TVPRRYSEFHALHKRIKK---RYKVPDFPSKRLPN 70
Cdd:cd06877    5 VSIPYVEM-----RRDPSNGEriYVFCIEVERNDRRAkghepqhwSVLRRYNEFYVLESKLTEfhgEFPDAPLPSRRIFG 79

                         90       100
                 ....*....|....*....|..
gi 564364315  71 WRTRG-LEQRRQGLETYIQGVL 91
Cdd:cd06877   80 PKSYEfLESKREIFEEFLQKLL 101