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 1730147869 296 FLEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDEVI 375
Cdd:cd07295     1 FLEIEVRNPKTHGIGRGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVI 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1730147869 376 ESRREGLERFLQVVAGHPLLQTGSKVMAAFLQDGGW 411
Cdd:cd07295    81 EERRQGLETFLQSVAGHPLLQTGSKVLAAFLQDPKF 116

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 1730147869 296 FLEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDEVI 375
Cdd:cd07295     1 FLEIEVRNPKTHGIGRGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVI 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1730147869 376 ESRREGLERFLQVVAGHPLLQTGSKVMAAFLQDGGW 411
Cdd:cd07295    81 EERRQGLETFLQSVAGHPLLQTGSKVLAAFLQDPKF 116

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 1730147869  303 NPLTHGVGRKMYTDYEIVTRTNipafkLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVF---TNRFTDEVIESRR 379
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKTG-----LEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLfgrLNNFSEEFIEKRR 77

                           90       100
                   ....*....|....*....|....*...
gi 1730147869  380 EGLERFLQVVAGHPLLQTGSKVMAAFLQ 407
Cdd:smart00312  78 RGLEKYLQSLLNHPELINHSEVVLEFLE 105

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 1730147869 296 FLEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDEVI 375
Cdd:cd07295     1 FLEIEVRNPKTHGIGRGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEVI 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1730147869 376 ESRREGLERFLQVVAGHPLLQTGSKVMAAFLQDGGW 411
Cdd:cd07295    81 EERRQGLETFLQSVAGHPLLQTGSKVLAAFLQDPKF 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3; 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. SNX3 associates with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P). It 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. SNX3 is required for the formation of multivesicular bodies, which function as transport intermediates to late endosomes. It also promotes cell surface expression of the amiloride-sensitive epithelial Na+ channel (ENaC), which is critical in sodium homeostasis and maintenance of extracellular fluid volume.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 296 FLEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILEREStRVNIPPLPGKVFTNR------ 369
Cdd:cd07293     1 FLEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERES-KVVVPPLPGKALFRQlpfrgd 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1730147869 370 ---FTDEVIESRREGLERFLQVVAGHPLLQTgSKVMAAFLQD 408
Cdd:cd07293    80 dgiFDDSFIEERKQGLEQFLNKVAGHPLAQN-ERCLHMFLQD 120

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 255 PGYPLPASNYTIPA--------YSPFA--RVDS---LSTPRRETVEDMYGVPENFLEVEVRNPLTHGVG---RKMYTDYE 318
Cdd:COG5391    76 PPPGGHTISYTIAIhdskihsrASEFRslRDMLsllLPTSLQPPLSTSHTILDYFISSTVSNPQSLTLLvdsRDKHTSYE 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 319 IVTRTNIPAFKLRYS---SVRRRYSDFEYFRDILERESTRVNIPPLPGK-----VFTNRFTDEVIESRREGLERFLQVVA 390
Cdd:COG5391   156 IITVTNLPSFQLRESrplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKksnseYYGDRFSDEFIEERRQSLQNFLRRVS 235

                         170       180
                  ....*....|....*....|....*.
gi 1730147869 391 GHPLL---------QTGSKVMAAFLQ 407
Cdd:COG5391   236 THPLLsnyknskswESHSTLLSSFIE 261

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 1730147869  303 NPLTHGVGRKMYTDYEIVTRTNipafkLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVF---TNRFTDEVIESRR 379
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKTG-----LEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLfgrLNNFSEEFIEKRR 77

                           90       100
                   ....*....|....*....|....*...
gi 1730147869  380 EGLERFLQVVAGHPLLQTGSKVMAAFLQ 407
Cdd:smart00312  78 RGLEKYLQSLLNHPELINHSEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; 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. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 299 VEVRNPLTHGVGRK-MYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDE-VIE 376
Cdd:cd06898     2 VEVRDPRTHKEDDWgSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNNEgFIE 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1730147869 377 SRREGLERFLQVVAGHPLLQTGSkVMAAFLQ 407
Cdd:cd06898    82 ERQQGLQDFLEKVLQTPLLLSDS-RLHLFLQ 111

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and 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. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 298 EVEVRNPLTHGVGRKMYTDYEIVTRTNipafKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDEVIES 377
Cdd:cd06093     1 SVSIPDYEKVKDGGKKYVVYIIEVTTQ----GGEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEE 76

                          90       100       110
                  ....*....|....*....|....*....|
gi 1730147869 378 RREGLERFLQVVAGHPLLQTgSKVMAAFLQ 407
Cdd:cd06093    77 RRKQLEQYLQSLLNHPELRN-SEELKEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; 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. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 297 LEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGK----VFTNRFTD 372
Cdd:cd06860     1 LFITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKhsvkGLLDRFSP 80

                          90       100
                  ....*....|....*....|...
gi 1730147869 373 EVIESRREGLERFLQVVAGHPLL 395
Cdd:cd06860    81 EFVATRMRALHKFLNRIVEHPVL 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 7; 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. SNX7 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, SNX30, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX7 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 299 VEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKV----FTNRFTDEV 374
Cdd:cd07284     3 ITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFvmkgMVERFNEDF 82

                          90       100
                  ....*....|....*....|.
gi 1730147869 375 IESRREGLERFLQVVAGHPLL 395
Cdd:cd07284    83 IETRRKALHKFLNRIADHPTL 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; 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. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 314 YTDYEIVTR----TNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGK--------VFTNRFTDEVIESRREG 381
Cdd:cd06864    23 YTVYLIETKivehESEEGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKramfmwqkLSSDTFDPDFVERRRAG 102

                          90       100
                  ....*....|....*....|....*..
gi 1730147869 382 LERFLQVVAGHPLLQTgSKVMAAFLQD 408
Cdd:cd06864   103 LENFLLRVAGHPELCQ-DKIFLEFLTH 128

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 1730147869 297 LEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDF-EYFRDILERESTRVNI-PPLPGKVFT------- 367
Cdd:cd07281     1 LKVSITDPEKIGDGMNAYVVYKVTTQTSLLMFRSKHFTVKRRFSDFlGLYEKLSEKHSQNGFIvPPPPEKSLIgmtkvkv 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1730147869 368 ---NRFTDEVIESRREGLERFLQVVAGHP-LLQ 396
Cdd:cd07281    81 gkeDSSSAEFLERRRAALERYLQRIVSHPsLLQ 113

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 297 LEVEVRNPLTHGVGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVN--IPPLPGKVFT------- 367
Cdd:cd07282     1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGyiVPPAPEKSIVgmtkvkv 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1730147869 368 ---NRFTDEVIESRREGLERFLQVVAGHP-LLQ 396
Cdd:cd07282    81 gkeDSSSTEFVEKRRAALERYLQRTVKHPtLLQ 113

The phosphoinositide binding Phox Homology domain of SNX-like 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 309 VGRKMYTDYEIVTRTNIPAFKLRYSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVF---TNRFTDEVIESRREGLERF 385
Cdd:cd06865    18 LGGPPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVvesQVMQSAEFIEQRRVALEKY 97

                          90
                  ....*....|
gi 1730147869 386 LQVVAGHPLL 395
Cdd:cd06865    98 LNRLAAHPVI 107

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 311 RKMYTDYEIVTrtnipafKLRYSS--VRRRYSDFEYFRDILERESTRVNIPpLPGK-VFTNRFTDEVIESRREGLERFLQ 387
Cdd:cd06870    17 KKRFTVYKVVV-------SVGRSSwfVFRRYAEFDKLYESLKKQFPASNLK-IPGKrLFGNNFDPDFIKQRRAGLDEFIQ 88

                          90       100
                  ....*....|....*....|
gi 1730147869 388 VVAGHPLLQTGSKVmAAFLQ 407
Cdd:cd06870    89 RLVSDPKLLNHPDV-RAFLQ 107

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; 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. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 310 GRKMYTDYEIV-TRTNIPafklryssVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDEVIESRREGLERFLQV 388
Cdd:cd07286    16 GMKSYISYKLVpSHTGLQ--------VHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKGLIWWMDH 87

                  ....*..
gi 1730147869 389 VAGHPLL 395
Cdd:cd07286    88 MCSHPVL 94

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1730147869 334 SVRRRYSDFeYfrdILERESTRVNIP----PLPGKVFTNRFTDEVIESRREGLERFLQVVAGHPLLQtGSKVMAAFL 406
Cdd:cd06877    45 SVLRRYNEF-Y---VLESKLTEFHGEfpdaPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKPELR-GSELLYDFL 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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 338 RYSDFEYFRDILERESTRVNIPPLPGKVFTnRFTDEVIESRREGLERFLQVVAGHPLLqTGSKVMAAFLQ 407
Cdd:cd06885    34 RYSQLHGLNEQLKKEFGNRKLPPFPPKKLL-PLTPAQLEERRLQLEKYLQAVVQDPRI-ANSDIFNSFLL 101

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 294 ENFLEVEVRNPLTHGVGRKMYTDYEI-VTRTNIPAFKLRYSsVRRRYSDF-EYFRDILERESTRVNIPpLPGKVFTNRFT 371
Cdd:cd06873     2 KFKLTAVIINTGIVKEHGKTYAVYAIsVTRIYPNGQEESWH-VYRRYSDFhDLHMRLKEKFPNLSKLS-FPGKKTFNNLD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1730147869 372 DEVIESRREGLERFLQ------VVAGHPLLQTgskVMAAFLQDG 409
Cdd:cd06873    80 RAFLEKRRKMLNQYLQsllnpeVLDANPGLQE---IVLDFLEPG 120

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1730147869 337 RRYSDFEYFRDILERESTRVNIPPLPGK-VFTnrFTDEVIESRREGLERFLQVVAGHPLLQTgSKVMAAFLQD 408
Cdd:cd06886    36 RRYREFANLHQNLKKEFPDFQFPKLPGKwPFS--LSEQQLDARRRGLEQYLEKVCSIRVIGE-SDIMQDFLSD 105

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 317 YEIVT-RTNIPAFKLR-------YSSVRRRYSDFEYFRDILERESTRVNIPPLPGKVFTNRFTDEVIESRREGLERFLQV 388
Cdd:cd07276    11 YEVMEeRARFTVYKIRvenkvgdSWFVFRRYTDFVRLNDKLKQMFPGFRLSLPPKRWFKDNFDPDFLEERQLGLQAFVNN 90

                          90
                  ....*....|...
gi 1730147869 389 VAGHPLLQTGSKV 401
Cdd:cd07276    91 IMAHKDIAKCKLV 103

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1730147869 308 GVGRKMYTDYEIvtRTNIPAFKLrysSVRRRYSDFEYFRDILERESTRVNIPPLPGK-VFTNRfTDEVIESRREGLERFL 386
Cdd:cd06874    12 GQGKDEHFEFEV--KITVLDETW---TVFRRYSRFRELHKTMKLKYPEVAALEFPPKkLFGNK-SERVAKERRRQLETYL 85

                  .
gi 1730147869 387 Q 387
Cdd:cd06874    86 R 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1730147869 334 SVRRRYSDFEYFRDILERE-STRVNIPPlPGKVFTNRFTDeVIESRREGLERFLQVVAGhpLLQTG-SKVMAAFL 406
Cdd:cd06875    32 TVKHRYSDFAELHDKLVAEhKVDKDLLP-PKKLIGNKSPS-FVEKRRKELEIYLQTLLS--FFQKTmPRELAHFL 102