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 62122887  41 MEISVAEAEKRTGKNAVNMQETYTVYLIETRPVDAASE-GTSPVPDSLWRRYSEFELLRNYLLVTYPFVVVPPLPEKRAE 119
Cdd:cd06864   1 MEITVTEAEKRTGGSAMNLKETYTVYLIETKIVEHESEeGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 62122887 120 FVWHKLSADNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd06864  81 FMWQKLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLTHE 129

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 62122887  41 MEISVAEAEKRTGKNAVNMQETYTVYLIETRPVDAASE-GTSPVPDSLWRRYSEFELLRNYLLVTYPFVVVPPLPEKRAE 119
Cdd:cd06864   1 MEITVTEAEKRTGGSAMNLKETYTVYLIETKIVEHESEeGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 62122887 120 FVWHKLSADNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd06864  81 FMWQKLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLTHE 129

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887    86 SLWRRYSEFELLRNYLLVTYPFVVVPPLPEKRAEFvwhklsadNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFL 165
Cdd:pfam00787  10 SVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLG--------RYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

                  ...
gi 62122887   166 TEE 168
Cdd:pfam00787  82 ESD 84

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 62122887  41 MEISVAEAEKRTGKNAVNMQETYTVYLIETRPVDAASE-GTSPVPDSLWRRYSEFELLRNYLLVTYPFVVVPPLPEKRAE 119
Cdd:cd06864   1 MEITVTEAEKRTGGSAMNLKETYTVYLIETKIVEHESEeGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 62122887 120 FVWHKLSADNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd06864  81 FMWQKLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLTHE 129

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887  17 LTPSESQNNLKntmvEKGTSLLKKMEISVAEAEKRTgknaVNMQE--TYTVYLIETRPVDAASEGTSPVPDSLWRRYSEF 94
Cdd:COG5391 111 LLPTSLQPPLS----TSHTILDYFISSTVSNPQSLT----LLVDSrdKHTSYEIITVTNLPSFQLRESRPLVVRRRYSDF 182

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887  95 ELLRNYLLVTYPFVVVPPLPEKRaefVWHKLSADNMDPDFVERRRVGLENFLLRVASHPVLARDNifylfltEEKAWKE- 173
Cdd:COG5391 183 ESLHSILIKLLPLCAIPPLPSKK---SNSEYYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYK-------NSKSWESh 252

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887 174 -TVFETGFQ---AKADSRLKALNATFR-----VKNPDKRFAE----MKHYGDELQAVVSQLLRVRARAADRLYGVYKVHg 240
Cdd:COG5391 253 sTLLSSFIEnrkSVPTPLSLDLTSTTQeldmeRKELNESTSKaihnILSIFSLFEKILIQLESEEESLTRLLESLNNLL- 331

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887 241 NYGRVFSE--WSAIEKEMGDGLQSaGHHMDAYAASI--------DDILEEEEHYADQLKEYLFYADALRAvcRKHELTQY 310
Cdd:COG5391 332 LLVLNFSGvfAKRLEQNQNSILNE-GVVQAETLRSSlkelltqlQDEIKSRESLILTDSNLEKLTDQNLE--DVEELSRS 408

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887 311 ELETAVQDLSSkkQQREELATGtvrtFSLKGMTSKLFGQETPEQReaKLKMLETQIEEGEEMVKDRNVECEEFVKGAWTD 390
Cdd:COG5391 409 LRKNSSQRAVV--SQQPEGLTS----FSKLSYKLRDFVQEKSRSK--SIESLQQDKEKLEEQLAIAEKDAQEINEELKNE 480

                       410       420       430       440
                ....*....|....*....|....*....|....*....|..
gi 62122887 391 IERFKEQKDHDLREALISYAIMQISMCKKGIQVWNNAKECFS 432
Cdd:COG5391 481 LKFFFSVRNSDLEKILKSVADSHIEWAEENLEIWKSVKEQLD 522

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 62122887  41 MEISVAEAEKRT-GKNAvnmqetYTVYLIETR---PVDAASEGtspvpdSLWRRYSEFELLRNYLLVTYPFVVVPPLPEK 116
Cdd:cd06859   1 FEISVTDPVKVGdGMSA------YVVYRVTTKtnlPDFKKSEF------SVLRRYSDFLWLYERLVEKYPGRIVPPPPEK 68

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 62122887 117 RAefvwhkLSADNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd06859  69 QA------VGRFKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

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 62122887  60 QETYTVYLIETRPVDAASEGTSPvpdSLWRRYSEFELLRNYLLVTYPFVVVPPLPEK-RAEFvwhkLSADNMDPDFVERR 138
Cdd:cd06863  16 SDTYISYLITTKTNLPSFSRKEF---KVRRRYSDFVFLHECLSNDFPACVVPPLPDKhRLEY----ITGDRFSPEFITRR 88

                        90       100
                ....*....|....*....|....*...
gi 62122887 139 RVGLENFLLRVASHPVLARDNIFYLFLT 166
Cdd:cd06863  89 AQSLQRFLRRISLHPVLSQSKILHQFLE 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887  63 YTVYLIETRpvdaasEGTSPVPdslwRRYSEFELLRNYLLVTYPFVVVPPLPEKRAefvwhklsADNMDPDFVERRRVGL 142
Cdd:cd06866  18 HVEYEVSSK------RFKSTVY----RRYSDFVWLHEYLLKRYPYRMVPALPPKRI--------GGSADREFLEARRRGL 79

                        90       100
                ....*....|....*....|....*
gi 62122887 143 ENFLLRVASHPVLARDNIFYLFLTE 167
Cdd:cd06866  80 SRFLNLVARHPVLSEDELVRTFLTE 104

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887  63 YTVYLIETRPvdaasegTSPVPD----SLWRRYSEFELLRNYLLVTYPFVVVPPLPEKRaefvwhklSADNMDPDFVERR 138
Cdd:cd06861  18 HTVYTVRTRT-------TSPNFEvssfSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQ--------SVGRFDDNFVEQR 82

                        90       100       110
                ....*....|....*....|....*....|
gi 62122887 139 RVGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd06861  83 RAALEKMLRKIANHPVLQKDPDFRLFLESE 112

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 62122887  89 RRYSEFELLRNYLLVTYPFVVVPPLPEKRAEFVWHKlsadnmdpDFVERRRVGLENFLLRVASHPVLARDNIFYLFLT-- 166
Cdd:cd06862  36 RRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEE--------DFIEKRRERLELWMNRLARHPVLSQSEVFRHFLTct 107

                ....*..
gi 62122887 167 EEKAWKE 173
Cdd:cd06862 108 DEKDWKS 114

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 62122887 193 ATFRVKNPDKRFAEMKHYGDELQAVVSQLLRVRAR-AADRLYGVYKVHgNYGRVFSEWSAIEKEMGDGLQSAGHHMDAYA 271
Cdd:cd07624   5 TMYLLKNRSPEFDKMNEYLTLFGEKLGTIERISQRiHKERIEYFDELK-EYSPIFQLWSASETELAPLLEGVSSAVERCT 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887 272 ASIDDILEEEEH-YADQLKEYLFYADALRAVCRKHELTQYELETAVQDLSSKKqqreelatgtvrtfslkgmtsklfgQE 350
Cdd:cd07624  84 AALEVLLSDHEFvFLPPLREYLLYSDAVKDVLKRRDQFQIEYELSVEELNKKR-------------------------LE 138

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62122887 351 TPEQREAklkmLETQIEEGEEMVKdrnveceefvkgawTDIERFKEQKDHDLREALISYAIMQISMCKKGIQVW 424
Cdd:cd07624 139 LLKEVEK----LQDKLECANADLK--------------ADLERWKQNKRQDLKKILLDMAEKQIQYYEQCLAAW 194

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 62122887  63 YTVY--LIETRPvdaaSEGTSPVpdsLWRRYSEFELLRNYLLVTYP---FVVVPPLPEKRaefVWHkLSADNMDPDFVER 137
Cdd:cd07280  22 YVVWkiTIETKD----LIGSSIV---AYKRYSEFVQLREALLDEFPrhkRNEIPQLPPKV---PWY-DSRVNLNKAWLEK 90

                        90
                ....*....|....*....
gi 62122887 138 RRVGLENFLLRVASHPVLA 156
Cdd:cd07280  91 RRRGLQYFLNCVLLNPVFG 109

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 62122887  57 VNMQETYTVYLIETRPVDAASEGTSpvpDSLWRRYSEFELLRNYLLVTYPFVVVPPLPEKraeFVWHKLsADNMDPDFVE 136
Cdd:cd07284  12 VTAIETFITYRVMTKTSRSEFDSSE---FEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEK---FVMKGM-VERFNEDFIE 84

                        90       100       110
                ....*....|....*....|....*....|..
gi 62122887 137 RRRVGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd07284  85 TRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 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 62122887  86 SLWRRYSEFELLRNYLLVTyPFVVVPPLPEKRAEFVWHKLSADNM-DPDFVERRRVGLENFLLRVASHPVLARDNIFYLF 164
Cdd:cd06894  39 SVRRRYSDFEWLRSELERD-SKIVVPPLPGKALKRQLPFRGDDGIfEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMF 117

                ....*
gi 62122887 165 LTEEK 169
Cdd:cd06894 118 LQEET 122

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 62122887  62 TYTVYLIETRPVDAASEGTspvpdsLWRRYSEFELLRNYLLVTYPfVVVPPLPEKrAEFVWHKLSADN--MDPDFVERRR 139
Cdd:cd07293  21 TYEIRLKTNLPIFKLKEST------VRRRYSDFEWLRSELERESK-VVVPPLPGK-ALFRQLPFRGDDgiFDDSFIEERK 92

                        90       100
                ....*....|....*....|....*....
gi 62122887 140 VGLENFLLRVASHPVLARDNIFYLFLTEE 168
Cdd:cd07293  93 QGLEQFLNKVAGHPLAQNERCLHMFLQDE 121

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; 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. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62122887  82 PVPDSLW---RRYSEFELLRNYLLVTYpfvVVPPLPEKraefvwhKLSAdNMDPDFVERRRVGLENFLLRVASHPVLAR 157
Cdd:cd06871  32 PSPENSWqviRRYNDFDLLNASLQISG---ISLPLPPK-------KLIG-NMDREFIAERQQGLQNYLNVILMNPILAS 99

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 62122887  63 YTVYLIETrpvdaaSEGTSPVpdSLWRRYSEFELLRNYLLVTYPFVVVPpLPEKRaefvwhkLSADNMDPDFVERRRVGL 142
Cdd:cd06870  20 FTVYKVVV------SVGRSSW--FVFRRYAEFDKLYESLKKQFPASNLK-IPGKR-------LFGNNFDPDFIKQRRAGL 83

                        90       100
                ....*....|....*....|....
gi 62122887 143 ENFLLRVASHPVLARDNIFYLFLT 166
Cdd:cd06870  84 DEFIQRLVSDPKLLNHPDVRAFLQ 107

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887  89 RRYSEFELLRNYLLVTYPfVVVPPLPEKRAEFVWHKLSADNM-DPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLTE 167
Cdd:cd07294  44 RRYSDFEWLKNELERDSK-IVVPPLPGKALKRQLPFRGDEGIfEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQD 122

                .
gi 62122887 168 E 168
Cdd:cd07294 123 E 123

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887  32 EKGTSLLKKMEISVaeaekrtgKNAVNMQET----YTVYLIETRPVDAASEGTSpvpdslW---RRYSEFELLRNYLLVT 104
Cdd:cd06876  11 ENDNSLYGRTRVSI--------QSYISDVEEegkeFVVYLIEVQRLNNDDQSSG------WvvaRRYSEFLELHKYLKKR 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 62122887 105 YPFVVVPPLPEKRaefvwhKLSADNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLT 166
Cdd:cd06876  77 YPGVLKLDFPQKR------KISLKYSKTLLVEERRKALEKYLQELLKIPEVCEDEEFRKFLS 132

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 62122887  89 RRYSEFELLRNYLLVTYP---FVVVPPlPEKrAEFVWHKLSADNMDP---DFVERRRVGLENFLLRVASHPVLARDNIFY 162
Cdd:cd07281  41 RRFSDFLGLYEKLSEKHSqngFIVPPP-PEK-SLIGMTKVKVGKEDSssaEFLERRRAALERYLQRIVSHPSLLQDPDVR 118

                ....*.
gi 62122887 163 LFLTEE 168
Cdd:cd07281 119 EFLEKE 124

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 62122887  90 RYSEFELLRNYLLVTYPFVV-VPPLPEKRAefvwhklsADNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLT-- 166
Cdd:cd07285  37 RYKHFDWLYERLLVKFGLAIpIPSLPDKQV--------TGRFEEEFIKMRMERLQAWMTRMCRHPVISESEVFQQFLNfr 108

                ....*.
gi 62122887 167 EEKAWK 172
Cdd:cd07285 109 DEKEWK 114

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62122887  89 RRYSEFELLRNYLLVTYPFVVVPPLPeKRAEFVwhklsadnMDPDFVERRRVgLENFLLRVASHPVLARDNIFYLFL 165
Cdd:cd06868  51 KKYSEFEELYKKLSEKYPGTILPPLP-RKALFV--------SESDIRERRAA-FNDFMRFISKDEKLANCPELLEFL 117

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Atg20p; 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 function of Atg20p is unknown but it has been shown to interact with Atg11p, which plays a role in linking cargo molecules with vesicle-forming components. 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 62122887 200 PDKRFAEMKHYGDELQAVVSQ-LLRVRARAADRLYGVYKVHGNYGRVFSEWSAIE--KEMGDGLQSAGHHMDAYAASIDD 276
Cdd:cd07629   2 PDDEFTDIEAETKKYEQLLHGgMEKVNRRITKRLGDLAEDMADLGGRFNAFSLEEqkSELAEALEKVGQAVDSTYLATEA 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62122887 277 ILEE-EEHYADQLKEYLFYADALRAVC--RKHELTQYEletavqdlsskkqqreelatgtvrtfslkgMTSKlfgqetpe 353
Cdd:cd07629  82 LVGSlYYNINEPLSESAQFAGVVRELLkyRKLKHVQYE------------------------------MTKD-------- 123

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62122887 354 qreaklKMLETQIEEGEEMVKDRNVECEefvkgawTDIERFKEQKDHDLREALISYAIMQISMCKKGIQVWNNAK 428
Cdd:cd07629 124 ------SLLESALVAASDDLVISSTIKQ-------KDLPRFQREREADLREILKNYSKYHKDWAKQNLEAWKEAK 185

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 62122887  63 YTVYLIETRPVDAAS-EGTSPVpdSLWRRYSEFELLRNYLLVTY-------PFvvvPPLPEKRAeFvwhklsaDNMDPDF 134
Cdd:cd06881  17 YTEYKITSKVFSRSVpEDVSEV--VVWKRYSDFKKLHRELSRLHkqlylsgSF---PPFPKGKY-F-------GRFDAAV 83