The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  18 LQCLVTEPRKELQGSRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLEYIKGGRF 97
Cdd:cd06863   1 LECLVSDPQKELDGSSDTYISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLEYITGDRF 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 19114817  98 SDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFLENP 135
Cdd:cd06863  81 SPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFLESS 118

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 19114817     22 VTEPRKeLQGSRDTHVSYLIITKTNLSiftraECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLEyiKGGRFSDNF 101
Cdd:smart00312   1 VVEPEK-IGDGKHYYYVIEIETKTGLE-----EWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFG--RLNNFSEEF 72

                           90       100       110
                   ....*....|....*....|....*....|...
gi 19114817    102 INRRAKLLNRYITRCALHPVLHQ-SPHFIAFLE 133
Cdd:smart00312  73 IEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  18 LQCLVTEPRKELQGSRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLEYIKGGRF 97
Cdd:cd06863   1 LECLVSDPQKELDGSSDTYISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLEYITGDRF 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 19114817  98 SDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFLENP 135
Cdd:cd06863  81 SPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFLESS 118

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 19114817  18 LQCLVTEPRKELqGSRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLeyiKG--G 95
Cdd:cd06860   1 LFITVDNPEKHV-TTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSV---KGllD 76

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 19114817  96 RFSDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFL 132
Cdd:cd06860  77 RFSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817    47 LSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLeyikgGRFSDNFINRRAKLLNRYITRCALHPVLHQSP 126
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWL-----GRYNEEFIEKRRKGLEQYLQRLLQHPELRNSE 75

                  ....*....
gi 19114817   127 HFIAFLENP 135
Cdd:pfam00787  76 VLLEFLESD 84

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 19114817  18 LQCLVTEPRKELQGsRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSR--MNEDCVVPPLPAKH-----KLE 90
Cdd:cd07282   1 IEIGVSDPEKVGDG-MNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASkyLHVGYIVPPAPEKSivgmtKVK 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 19114817  91 YIKGGRFSDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFLEN 134
Cdd:cd07282  80 VGKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 123

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Atg24p; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. Atg24p is involved in membrane fusion events at the vacuolar surface during pexophagy. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 175 EFDIQRDHVQQFMFGISNLEGSIQKLLRLEKALESDYEDVSIQFDRLASLDQA-LDVPIESIQNALQQTGTEYANLTEKL 253
Cdd:cd07628   5 EFLEIREKSDKLDENLTKIDKIFAKVVKRQSDLSVDYADLATQFQKLGSLESGeITEPFKIFSESLSQFSTSLRVLNKYT 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 254 TL-LLDTIKDVESYAHSLKELLKRRDQKQQDVEALQEYsaklsLERDkissggsngfslsktlddlrgidhndtrlkrle 332
Cdd:cd07628  85 DEnYLTSLKDLLHYILSLKNLIKLRDQKQLDYEELSDY-----LLTD--------------------------------- 126

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19114817 333 hvqselqAVEQAiQEASavhDAFNQRVREESKLFDSVRQSEMLSAISDYANVHVEFFTNIRDLWIRV 399
Cdd:cd07628 127 -------EVENA-KETS---DAFNKEVLKEYPNFERIKKQEIKDSLGALADGHIDFYQGLVEDWEKV 182

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 19114817  22 VTEPRKELQGsRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNED--CVVPPLPAKH-----KLEYIKG 94
Cdd:cd07281   5 ITDPEKIGDG-MNAYVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEKHSQngFIVPPPPEKSligmtKVKVGKE 83

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 19114817  95 GRFSDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFLE 133
Cdd:cd07281  84 DSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVREFLE 122

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 19114817  17 FLQCLVTEPRKELQGsRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKhkleyIKGGR 96
Cdd:cd07295   1 FLEIEVRNPKTHGIG-RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGK-----IFTNR 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 19114817  97 FSDNFINRRAKLLNRYITRCALHPVLHQ-SPHFIAFLENPNW 137
Cdd:cd07295  75 FSDEVIEERRQGLETFLQSVAGHPLLQTgSKVLAAFLQDPKF 116

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  17 FLQCLVTEPRKELQGsRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRmNEDCVVPPLPAK---HKLEYIK 93
Cdd:cd06894   1 FLEIDVVNPQTHGVG-KKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELER-DSKIVVPPLPGKalkRQLPFRG 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 19114817  94 G-GRFSDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFLENP 135
Cdd:cd06894  79 DdGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEE 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  22 VTEPRKELQgSRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLEYIKgGRFSDNF 101
Cdd:cd07283   5 VDDPKKHVC-TMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVV-DRFSEEF 82

                        90       100       110
                ....*....|....*....|....*....|.
gi 19114817 102 INRRAKLLNRYITRCALHPVLHQSPHFIAFL 132
Cdd:cd07283  83 VETRRKALDKFLKRIADHPVLSFNEHFNVFL 113

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 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. This subfamily consists of SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while 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 19114817  19 QCLVTEPRKE--LQGSRdTHVSYLII-TKTNLSiftraeckVRRRFSDFVKLQEILSRMNEDCVVPPLPAKhklEYikGG 95
Cdd:cd06862   2 HCTVTNPKKEskFKGLK-SFIAYQITpTHTNVT--------VSRRYKHFDWLYERLVEKYSCIAIPPLPEK---QV--TG 67

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 19114817  96 RFSDNFINRRAKLLNRYITRCALHPVLHQSP---HFIAFLENPNWNNYVR 142
Cdd:cd06862  68 RFEEDFIEKRRERLELWMNRLARHPVLSQSEvfrHFLTCTDEKDWKSGKR 117

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 171 EEPTEFDIQRDHVQQFMFGISNLEGSIQKLLRLEKALESDYEDVSIQFDRLASLD----QALDVPIESIQNALQQTGTEY 246
Cdd:cd07596   1 EEDQEFEEAKDYILKLEEQLKKLSKQAQRLVKRRRELGSALGEFGKALIKLAKCEeevgGELGEALSKLGKAAEELSSLS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 247 ANLTEKLTL-LLDTIKDVESYAHSLKELLKRRDQKQQDVEALQEY--SAKLSLERDKISSGgsngfslsktlddlrgidh 323
Cdd:cd07596  81 EAQANQELVkLLEPLKEYLRYCQAVKETLDDRADALLTLQSLKKDlaSKKAQLEKLKAAPG------------------- 141

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19114817 324 ndTRLKRLEHVQSELQAVEQAIQEASAVHDAFNQRVREESKLFDSVRQSEMLSAISDYANVHVEFFTNIRDLW 396
Cdd:cd07596 142 --IKPAKVEELEEELEEAESALEEARKRYEEISERLKEELKRFHEERARDLKAALKEFARLQVQYAEKIAEAW 212

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 30; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. The specific function of SNX30 is still unknown. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 119 HPVLHQSPHFIAFLENPNWNNYVRffiqPKLNNTSKLDEISDSLLNAFsKLKEEPTEFDIQRDHVQQFMFGISNLEGSIQ 198
Cdd:cd07667   1 HPVLSFNEHFNVFLTAKDLNAYKK----QGIALLSKMGESVKYVTGGY-KLRSRPLEFAAIGDYLDTFALKLGTIDRIAQ 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 199 KLLRLEKALESDYEDVSIQFDRLASLDQALDVPIESIQNALQQTGTEYANLTEKLTL-LLDTIKDVESYAHSLKELLKRR 277
Cdd:cd07667  76 RIIKEEIEYLVELREYGPVYSTWSGLEGELAEPLEGVSACIGNCSTALEELTEDMTEdFLPVLREYILYSESMKNVLKKR 155

                       170       180
                ....*....|....*....|....*.
gi 19114817 278 DQKQQDVEALQEYSAKLSLERDKISS 303
Cdd:cd07667 156 DQVQAEYEAKLEAVALRKEERPKVPT 181

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 19114817  22 VTEPRKELQGSRDTHVSYLIITKTNLSIFTRAECKVRRRFSDFVKLQEILSRMNEDCVVPPLPAKHKLeyikgGRFSD-N 100
Cdd:cd06898   4 VRDPRTHKEDDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLF-----GRFNNeG 78

                        90       100       110
                ....*....|....*....|....*....|...
gi 19114817 101 FINRRAKLLNRYITRCALHPVLHQSPHFIAFLE 133
Cdd:cd06898  79 FIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQ 111

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; 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. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It 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. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  18 LQCLVTEPRKelqGSR----DTHVSY-LIITKTNLSiftraeckVRRRFSDFVKLQE-ILSRMNEDCVVPPLPAKHKLey 91
Cdd:cd07285   1 FDCVVADPRK---GSKmyglKSYIEYqLTPTNTNRS--------VNHRYKHFDWLYErLLVKFGLAIPIPSLPDKQVT-- 67

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 19114817  92 ikgGRFSDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFL 132
Cdd:cd07285  68 ---GRFEEEFIKMRMERLQAWMTRMCRHPVISESEVFQQFL 105

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 7 and 30; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. This subfamily consists of SNX7, SNX30, and similar proteins. The specific functions of SNX7 and SNX30 have not been elucidated. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817 165 AFSKLKEEPTEFDIQRDHVQQFMFGISNLEGSIQKLLRLEKALESDYEDVSIQFDRLASLDQALDVPIESIQNALQ--QT 242
Cdd:cd07624   5 TMYLLKNRSPEFDKMNEYLTLFGEKLGTIERISQRIHKERIEYFDELKEYSPIFQLWSASETELAPLLEGVSSAVErcTA 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 19114817 243 GTEyANLTEKLTLLLDTIKDVESYAHSLKELLKRRDQKQQD----VEALQEYSAKLSLERDKIS 302
Cdd:cd07624  85 ALE-VLLSDHEFVFLPPLREYLLYSDAVKDVLKRRDQFQIEyelsVEELNKKRLELLKEVEKLQ 147

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19114817  57 VRRRFSDFVKLQEILSRMnedcvVPPLPAKHKLEYIKGGRFSDNFINRRAKLLNRYITRCALHPVLHQSPHFIAFL 132
Cdd:cd06870  36 VFRRYAEFDKLYESLKKQ-----FPASNLKIPGKRLFGNNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  22 VTEPRKELQGSRDTHVSYLIITKTNLSIFTraECKVRRRFSDFVKLQEILSRMNEDCVVP-PLPAKHKLEYIkgGRFSDN 100
Cdd:cd06881   7 VTDTRRHKKGYTEYKITSKVFSRSVPEDVS--EVVVWKRYSDFKKLHRELSRLHKQLYLSgSFPPFPKGKYF--GRFDAA 82

                        90       100       110
                ....*....|....*....|....*....|...
gi 19114817 101 FINRRAKLLNRYITRCALHPVLHQSPHFIAFLE 133
Cdd:cd06881  83 VIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  22 VTEPRKELQGSrdTHVSYliitktNLSIFTRAECKVRrrFSDFVKLQEILSRMNEDCVVPPLPAKHKLeyikggRFSDNF 101
Cdd:cd06885   6 DTQELSDEGGS--TYVAY------NIHINGVLHCSVR--YSQLHGLNEQLKKEFGNRKLPPFPPKKLL------PLTPAQ 69

                        90       100       110
                ....*....|....*....|....*....|...
gi 19114817 102 INRRAKLLNRYITRCALHPVLHQSPHFIAFLEN 134
Cdd:cd06885  70 LEERRLQLEKYLQAVVQDPRIANSDIFNSFLLN 102

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  195 GSIQKLLR---LE-KALESDYEDVSIQFDRLASLDQALDVPIESIQ--NALQQTGTEYANLTEKLTLLLDTIKDVESYAH 268
Cdd:COG4913  207 GDLDDFVReymLEePDTFEAADALVEHFDDLERAHEALEDAREQIEllEPIRELAERYAAARERLAELEYLRAALRLWFA 286

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19114817  269 SLK-ELLKRR-DQKQQDVEALQEYSAKLSLERDKissggsngfsLSKTLDDLRG-IDHNDTRlkRLEHVQSELQAVEQAI 345
Cdd:COG4913  287 QRRlELLEAElEELRAELARLEAELERLEARLDA----------LREELDELEAqIRGNGGD--RLEQLEREIERLEREL 354