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 22327944 154 KITVSNPQKEQEISNSIVGGNTYITYQITTRTNLPDfGGPSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQ 233
Cdd:cd06865   1 KITVSDPKKEQEPSRVPLGGPPYISYKVTTRTNIPS-YTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 22327944 234 VMQKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQVQ 274
Cdd:cd06865  80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

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 22327944 154 KITVSNPQKEQEISNSIVGGNTYITYQITTRTNLPDfGGPSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQ 233
Cdd:cd06865   1 KITVSDPKKEQEPSRVPLGGPPYISYKVTTRTNIPS-YTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 22327944 234 VMQKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQVQ 274
Cdd:cd06865  80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

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 22327944    157 VSNPQKEQEisnsivGGNTYITYQITTRTNLpdfggpSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQVMQ 236
Cdd:smart00312   1 VVEPEKIGD------GKHYYYVIEIETKTGL------EEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNF 68

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 22327944    237 KQEFVEQRRVALEKYLRRLSAHPVIRN-SDELKVFLQ 272
Cdd:smart00312  69 SEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 153 IKITVSNPQKE-QEISNSivggNTYITYQITTRTNLPDFGGPSEF--SVRRRFRDVVTLADRLAETYRGFCIPPRPDKSV 229
Cdd:COG5391 131 ISSTVSNPQSLtLLVDSR----DKHTSYEIITVTNLPSFQLRESRplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKKS 206

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 230 VESQVMQK--QEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQVqgklplpmSTDVASrmldgavklPKQLFGeggas 307
Cdd:COG5391 207 NSEYYGDRfsDEFIEERRQSLQNFLRRVSTHPLLSNYKNSKSWESH--------STLLSS---------FIENRK----- 264

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 308 AVPVTEVGQPARGGRDLLRLFKELRQSVSNDWGGSKPPVVEEDKEFLeKKEKMHDLEQQIINASQQAESLVKAQQdmget 387
Cdd:COG5391 265 SVPTPLSLDLTSTTQELDMERKELNESTSKAIHNILSIFSLFEKILI-QLESEEESLTRLLESLNNLLLLVLNFS----- 338

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 388 mGELGLAFIKLTKFENEEAVCNPQRTRANDmknlataavkasrFYRELNSQTVKHldTLHEYLGMMMAVQGAFAD----- 462
Cdd:COG5391 339 -GVFAKRLEQNQNSILNEGVVQAETLRSSL-------------KELLTQLQDEIK--SRESLILTDSNLEKLTDQnledv 402

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 463 ----RSSALLTVQTL-LSELPSLQTrVEKLEAASSKVFGGDKSRIRKIEELKETIKVTEDAKNVAIKGYERIKENNRSEV 537
Cdd:COG5391 403 eelsRSLRKNSSQRAvVSQQPEGLT-SFSKLSYKLRDFVQEKSRSKSIESLQQDKEKLEEQLAIAEKDAQEINEELKNEL 481

                       410       420       430       440
                ....*....|....*....|....*....|....*....|...
gi 22327944 538 ERLDRERRADFMNMMKGFVVNQVGYAEKMGNVWAKVAEETSQY 580
Cdd:COG5391 482 KFFFSVRNSDLEKILKSVADSHIEWAEENLEIWKSVKEQLDRL 524

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 22327944 154 KITVSNPQKEQEISNSIVGGNTYITYQITTRTNLPDfGGPSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQ 233
Cdd:cd06865   1 KITVSDPKKEQEPSRVPLGGPPYISYKVTTRTNIPS-YTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQ 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 22327944 234 VMQKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQVQ 274
Cdd:cd06865  80 VMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

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 22327944 153 IKITVSNPQKEQEISNSivggntYITYQITTRTNLPDFGgPSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVES 232
Cdd:cd06859   1 FEISVTDPVKVGDGMSA------YVVYRVTTKTNLPDFK-KSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGR 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 22327944 233 qVMQKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd06859  74 -FKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLE 112

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 22327944 153 IKITVSNPQKEQEisnsiVGGNTYITYQITTRTNLPDFGGPsEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVES 232
Cdd:cd06863   1 LECLVSDPQKELD-----GSSDTYISYLITTKTNLPSFSRK-EFKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLEY 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 22327944 233 QVMQK--QEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFL 271
Cdd:cd06863  75 ITGDRfsPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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 22327944 153 IKITVSNPQKEQEisnsivGGNTYITYQITTRTNLPDFGgPSEFSVRRRFRDVVTLADRLAETYR--GFCIPPRPDKSVV 230
Cdd:cd07282   1 IEIGVSDPEKVGD------GMNAYMAYRVTTKTSLSMFS-RSEFSVRRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIV 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 22327944 231 E-------SQVMQKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd07282  74 GmtkvkvgKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 122

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 22327944 153 IKITVSNPQKEQEisnsivGGNTYITYQITTRTNLPDFGGpSEFSVRRRFRDVVTLADRLAETY--RGFCIPPRPDKSV- 229
Cdd:cd07281   1 LKVSITDPEKIGD------GMNAYVVYKVTTQTSLLMFRS-KHFTVKRRFSDFLGLYEKLSEKHsqNGFIVPPPPEKSLi 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 22327944 230 ------VESQVMQKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd07281  74 gmtkvkVGKEDSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVREFLE 122

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 22327944    157 VSNPQKEQEisnsivGGNTYITYQITTRTNLpdfggpSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQVMQ 236
Cdd:smart00312   1 VVEPEKIGD------GKHYYYVIEIETKTGL------EEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNF 68

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 22327944    237 KQEFVEQRRVALEKYLRRLSAHPVIRN-SDELKVFLQ 272
Cdd:smart00312  69 SEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

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 22327944 155 ITVSNPQKEqeisnsIVGGNTYITYQITTRTNLPDFGGPsEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQV 234
Cdd:cd07283   3 VTVDDPKKH------VCTMETYITYRVTTKTTRTEFDLP-EYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVV 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 22327944 235 MQ-KQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQVQ 274
Cdd:cd07283  76 DRfSEEFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

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 22327944 154 KITVSNPQKEQEISnsivGGNTYITYQITtrtnlpdfGGPSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKsvvesQ 233
Cdd:cd06862   2 HCTVTNPKKESKFK----GLKSFIAYQIT--------PTHTNVTVSRRYKHFDWLYERLVEKYSCIAIPPLPEK-----Q 64

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 22327944 234 VMQK--QEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd06862  65 VTGRfeEDFIEKRRERLELWMNRLARHPVLSQSEVFRHFLT 105

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 22327944 153 IKITVSNPQKEqeISNSIVG-GNTYITYQITTR---TNLPDFGGPSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKS 228
Cdd:cd06864   1 MEITVTEAEKR--TGGSAMNlKETYTVYLIETKiveHESEEGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKR 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 22327944 229 VveSQVMQK-------QEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd06864  79 A--MFMWQKlssdtfdPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLT 127

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 22327944 152 YIKITVSNPQkeqeisNSIVGGNTYITYQITTRTNLPDFGgPSEFSVRRRFRDVVTLADRLAETYRgFCIPPRPDKSVVE 231
Cdd:cd06894   1 FLEIDVVNPQ------THGVGKKRFTDYEVRMRTNLPVFK-KKESSVRRRYSDFEWLRSELERDSK-IVVPPLPGKALKR 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 22327944 232 SQVMQK------QEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd06894  73 QLPFRGddgifeEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQ 119

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 22327944 151 DYIKITVSNPQKEQeisnsiVGGNTYITYQITTRTNLPDFGgPSEFSVRRRFRDVVTLADRLaETYRGFCIPPRPDKSVV 230
Cdd:cd07294   2 NFLEIDIFNPQTVG------VGRNRFTTYEVRMRTNLPIFK-LKESCVRRRYSDFEWLKNEL-ERDSKIVVPPLPGKALK 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 22327944 231 ESQVMQKQE------FVEQRRVALEKYLRRLSAHPVIRNSDELKVFLQ 272
Cdd:cd07294  74 RQLPFRGDEgifeesFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQ 121

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 166 ISNSIVGGNTYITYQITTRTNLpdfggpSEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVeSQVMQKQEFVEQRR 245
Cdd:cd06897   5 IPTTSVSPKPYTVYNIQVRLPL------RSYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWF-LSTSSNPKLVEERR 77

                        90       100       110
                ....*....|....*....|....*....|.
gi 22327944 246 VALEKYLRRLSAHPV--IRNSDELKVFLQVQ 274
Cdd:cd06897  78 VGLEAFLRALLNDEDsrWRNSPAVKEFLNLP 108

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 22327944 176 YITYQITTRTNlpdfggpsEFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQvmqKQEFVEQRRVALEKYLRRL 255
Cdd:cd06866  18 HVEYEVSSKRF--------KSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSA---DREFLEARRRGLSRFLNLV 86

                        90
                ....*....|....*.
gi 22327944 256 SAHPVIRNSDELKVFL 271
Cdd:cd06866  87 ARHPVLSEDELVRTFL 102

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 171 VGGNTYITYQITTRTNLPDFGG--PSEFSVRRRFRDVVTLADRLAETYRGF---CIPPRpdksvvESQVMQKQEFVEQRR 245
Cdd:cd06877  17 SNGERIYVFCIEVERNDRRAKGhePQHWSVLRRYNEFYVLESKLTEFHGEFpdaPLPSR------RIFGPKSYEFLESKR 90

                        90       100
                ....*....|....*....|....*.
gi 22327944 246 VALEKYLRRLSAHPVIRNSDELKVFL 271
Cdd:cd06877  91 EIFEEFLQKLLQKPELRGSELLYDFL 116

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 1 and 2; 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 SNX1, SNX2, and similar proteins. 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 efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. 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 22327944 345 PVVEEDKEFLEKKEKMHDLEQQIINASQQAESLVKAQQDMGETMGELGLAFIKLTKFENEEAVcnpqrTRAndMKNLATA 424
Cdd:cd07623   6 KMDETDQWFEEKQQQIENLDQQLRKLHASVESLVNHRKELALNTGSFAKSAAMLSNCEEHTSL-----SRA--LSQLAEV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 425 AVKASRFYREL-NSQTVKHLDTLHEYLGMMMAVQGAFADRSSALLTVQTLLSELPSLQTRVEKLEAASskvfggdksRIR 503
Cdd:cd07623  79 EEKIEQLHGEQaDTDFYILAELLKDYIGLIGAIKDVFHERVKVWQNWQNAQQTLTKKREAKAKLELSG---------RTD 149

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22327944 504 KIEELKETIKVTEDAKNVAIKGYERIKENNRSEVERLDRERRADFMNMMKGFVVNQVGYAEKMGNVWAKVAEET 577
Cdd:cd07623 150 KLDQAQQEIKEWEAKVDRGQKEFEEISKTIKKEIERFEKNRVKDFKDIIIKYLESLLNTQQQLIKYWEAFLPEA 223

The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 164 QEISNSIVGGNtyITYQITTRTNLPDFGGPS-------EFSVRRRFRDVVTLADRLAETYRGFCIPPRPDKSVVESQVMq 236
Cdd:cd06868  10 QEIRGKTSSGH--VLYQIVVVTRLAAFKSAKhkeedvvQFMVSKKYSEFEELYKKLSEKYPGTILPPLPRKALFVSESD- 86

                        90       100       110
                ....*....|....*....|....*....|....*
gi 22327944 237 kqefVEQRRVALEKYLRRLSAHPVIRNSDELKVFL 271
Cdd:cd06868  87 ----IRERRAAFNDFMRFISKDEKLANCPELLEFL 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22327944 195 EFSVRRRFRDVVTLADRLAET--YRGFCIPPRPDKSVVE--SQVMQKQEfVEQRRVALEKYLRRLSAHPVIRNSDELKVF 270
Cdd:cd06893  50 THTVNRRFREFLTLQTRLEENpkFRKIMNVKGPPKRLFDlpFGNMDKDK-IEARRGLLETFLRQLCSIPEISNSEEVQEF 128

                .
gi 22327944 271 L 271
Cdd:cd06893 129 L 129

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 22327944 157 VSNPQKeqeiSNSIVGGNTYITYQIT-TRTNLPdfggpsefsVRRRFRDVVTLADRLAETY-RGFCIPPRPDKSVVESQv 234
Cdd:cd07285   5 VADPRK----GSKMYGLKSYIEYQLTpTNTNRS---------VNHRYKHFDWLYERLLVKFgLAIPIPSLPDKQVTGRF- 70

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 22327944 235 mqKQEFVEQRRVALEKYLRRLSAHPVIRNSDELKVFL 271
Cdd:cd07285  71 --EEEFIKMRMERLQAWMTRMCRHPVISESEVFQQFL 105