Domain associated with PX domains; unpubl. observations

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140    95 ERQLEQEIDRTIRMIMRDFVSSWYRTVSQEPAFEEEMEAAMRGLVQELRRRMAMVDRHALaqrVLTLCGCHLQSYIQ-AK 173
Cdd:smart00313    1 PAQLEEPLQLLISKIIRDYVQGWYKGVSEDPSFLREIEQTLEYILRQLYRRLSRQDSAHL---ILYEILKNLISTITnAL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140   174 EATAGQQSgTVEPSQLWEAYCRVTAPHPAVQSPSAEVTYTRGIVNAVLQGLVPKPHLETRTGRHVVVELITCNVILPLTS 253
Cdd:smart00313   78 EAVLRFAS-PQIPSTEIDLQYAETAIHKALSSPSNELTYRRQLVEMLLKFLLPEDSLCSRLHRCLLREVLAMQVILPLIT 156

                           170       180
                    ....*....|....*....|
gi 1768750140   254 KLSDPDWIHLVLVGIFSKAR 273
Cdd:smart00313  157 HLSDPDTINLCIILLFSSSR 176

Domain associated with PX domains; unpubl. observations

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140    95 ERQLEQEIDRTIRMIMRDFVSSWYRTVSQEPAFEEEMEAAMRGLVQELRRRMAMVDRHALaqrVLTLCGCHLQSYIQ-AK 173
Cdd:smart00313    1 PAQLEEPLQLLISKIIRDYVQGWYKGVSEDPSFLREIEQTLEYILRQLYRRLSRQDSAHL---ILYEILKNLISTITnAL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140   174 EATAGQQSgTVEPSQLWEAYCRVTAPHPAVQSPSAEVTYTRGIVNAVLQGLVPKPHLETRTGRHVVVELITCNVILPLTS 253
Cdd:smart00313   78 EAVLRFAS-PQIPSTEIDLQYAETAIHKALSSPSNELTYRRQLVEMLLKFLLPEDSLCSRLHRCLLREVLAMQVILPLIT 156

                           170       180
                    ....*....|....*....|
gi 1768750140   254 KLSDPDWIHLVLVGIFSKAR 273
Cdd:smart00313  157 HLSDPDTINLCIILLFSSSR 176

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  848 WLCTENM---RKVLHLIFGTLIQRWLEVQVANLTSPRRWVQYLRLLQESVWPGGVLPKcPRPVRTQEQKVAAEKQALQSL 924
Cdd:pfam08628    1 WLRRRALnalKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAE-PPPERTEEEKLRTRKEARKLL 79

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1768750140  925 MGVLPDVVVEILGVNRCRLGWSLVLESLQQP 955
Cdd:pfam08628   80 LSLIPDALGSVVGRENAREAARRVFDMLQNP 110

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 1768750140   549 ITAREHSGTGFHPYTLYTVKYETaldgessgglqQLAYHTVNRRYREFLNLQTRLeeksdLRKFiknvkgPKKLFPDLP- 627
Cdd:smart00312    1 VVEPEKIGDGKHYYYVIEIETKT-----------GLEEWTVSRRYSDFLELHSKL-----KKHF------PRSILPPLPg 58

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1768750140   628 ------FGNMDSDRVEARKSLLESFLKQLCAIPELAN-SEEVQEFL 666
Cdd:smart00312   59 kklfgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

Domain associated with PX domains; unpubl. observations

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140    95 ERQLEQEIDRTIRMIMRDFVSSWYRTVSQEPAFEEEMEAAMRGLVQELRRRMAMVDRHALaqrVLTLCGCHLQSYIQ-AK 173
Cdd:smart00313    1 PAQLEEPLQLLISKIIRDYVQGWYKGVSEDPSFLREIEQTLEYILRQLYRRLSRQDSAHL---ILYEILKNLISTITnAL 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140   174 EATAGQQSgTVEPSQLWEAYCRVTAPHPAVQSPSAEVTYTRGIVNAVLQGLVPKPHLETRTGRHVVVELITCNVILPLTS 253
Cdd:smart00313   78 EAVLRFAS-PQIPSTEIDLQYAETAIHKALSSPSNELTYRRQLVEMLLKFLLPEDSLCSRLHRCLLREVLAMQVILPLIT 156

                           170       180
                    ....*....|....*....|
gi 1768750140   254 KLSDPDWIHLVLVGIFSKAR 273
Cdd:smart00313  157 HLSDPDTINLCIILLFSSSR 176

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  848 WLCTENM---RKVLHLIFGTLIQRWLEVQVANLTSPRRWVQYLRLLQESVWPGGVLPKcPRPVRTQEQKVAAEKQALQSL 924
Cdd:pfam08628    1 WLRRRALnalKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAE-PPPERTEEEKLRTRKEARKLL 79

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1768750140  925 MGVLPDVVVEILGVNRCRLGWSLVLESLQQP 955
Cdd:pfam08628   80 LSLIPDALGSVVGRENAREAARRVFDMLQNP 110

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  582 QQLAYHTVNRRYREFLNLQTRLEEKSDLRKFiknvkgpkklfPDLP----FGNMDSDRVEARKSLLESFLKQLCAIPELA 657
Cdd:pfam00787    4 FSLEEWSVRRRYSDFVELHKKLLRKFPSVII-----------PPLPpkrwLGRYNEEFIEKRRKGLEQYLQRLLQHPELR 72

                   ....*....
gi 1768750140  658 NSEEVQEFL 666
Cdd:pfam00787   73 NSEVLLEFL 81

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  589 VNRRYREFLNLQTRLeeKSDLRKFIKNVKGPKKLFpdlpFGNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQEFLAL 668
Cdd:cd07279     38 IERRYSDFLKLYKAL--RKQHPQLMAKVSFPRKVL----MGNFSSELIAERSRAFEQFLGHILSIPNLRDSKAFLDFLQG 111

                   .
gi 1768750140  669 N 669
Cdd:cd07279    112 P 112

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 1768750140  545 ITGTITAREHSGTGFHPYTLYTVKYETALDgessggLQQLAYHTVNRRYREFLNLQTRLEEKSDLRKFI------KNVKG 618
Cdd:cd07281      1 LKVSITDPEKIGDGMNAYVVYKVTTQTSLL------MFRSKHFTVKRRFSDFLGLYEKLSEKHSQNGFIvppppeKSLIG 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1768750140  619 PKKlfpdLPFGNMDSDR---VEARKSLLESFLKQLCAIPELANSEEVQEFL 666
Cdd:cd07281     75 MTK----VKVGKEDSSSaefLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  591 RRYREFLNLQTRLeeksdlrkfiknvkgpKKLFPDLPFGNMDS--------DRVEARKSLLESFLKQLCAIPELANSEEV 662
Cdd:cd06886     36 RRYREFANLHQNL----------------KKEFPDFQFPKLPGkwpfslseQQLDARRRGLEQYLEKVCSIRVIGESDIM 99

                   ....*
gi 1768750140  663 QEFLA 667
Cdd:cd06886    100 QDFLS 104

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 1768750140  538 VVIQNlritgTITAREHSGTGFhpyTLYTVKYETALDGESSGGLqqlayhTVNRRYREFLNLQTRLEEKSDLrkfIKNVK 617
Cdd:cd06876     22 VSIQS-----YISDVEEEGKEF---VVYLIEVQRLNNDDQSSGW------VVARRYSEFLELHKYLKKRYPG---VLKLD 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1768750140  618 GPKKLFPDLPFGNmdSDRVEARKSLLESFLKQLCAIPELANSEEVQEFL 666
Cdd:cd06876     85 FPQKRKISLKYSK--TLLVEERRKALEKYLQELLKIPEVCEDEEFRKFL 131

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  545 ITGTITAREHSGTgfhpYTLY--TVKYETALDGESSgglqqlaYHTVnRRYREFLNLQTRLEEK-SDLRKfiknVKGPKK 621
Cdd:cd06873      9 IINTGIVKEHGKT----YAVYaiSVTRIYPNGQEES-------WHVY-RRYSDFHDLHMRLKEKfPNLSK----LSFPGK 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1768750140  622 LFpdlpFGNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQEFLA 667
Cdd:cd06873     73 KT----FNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVL 114

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  588 TVNRRYREFLNLQTRL--EEKSDlrkfiKNVKGPKKLFpdlpfGNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQEF 665
Cdd:cd06875     32 TVKHRYSDFAELHDKLvaEHKVD-----KDLLPPKKLI-----GNKSPSFVEKRRKELEIYLQTLLSFFQKTMPRELAHF 101

                   .
gi 1768750140  666 L 666
Cdd:cd06875    102 L 102

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 1768750140  549 ITAREHSGTGFHPYTLYTVKYETALDgessggLQQLAYHTVNRRYREFLNLQTRLEEKSDLrkFIKNVKGpKKLFPDLPF 628
Cdd:cd07293      6 VTNPQTVGVGRGRFTTYEIRLKTNLP------IFKLKESTVRRRYSDFEWLRSELERESKV--VVPPLPG-KALFRQLPF 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1768750140  629 ----GNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQEFL 666
Cdd:cd07293     77 rgddGIFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFL 118

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 1768750140  584 LAYHTVNRRYREFLNLQTRLEEKSDLRKfiknvkgPKKLFPDLPFGNMDSDR-VEARKSLLESFLKQLCAIPELANSEEV 662
Cdd:cd06898     34 LKTSCVRRRYSEFVWLRNRLQKNALLIQ-------LPSLPPKNLFGRFNNEGfIEERQQGLQDFLEKVLQTPLLLSDSRL 106

                   ....
gi 1768750140  663 QEFL 666
Cdd:cd06898    107 HLFL 110

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  542 NLRITGTItAREHSGTGFHPYTLYTVKYETaldgesSGGLQQLAYhtvnRRYREFLNLQTRLEEKSDLRKfiknVKGPK- 620
Cdd:cd06882      1 DVAVSATI-ADIEEKRGFTNYYVFVIEVKT------KGGSKYLIY----RRYRQFFALQSKLEERFGPEA----GSSAYd 65

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1768750140  621 KLFPDLP----FGNmDSDRVEARKSLLESFLKQLCAIP-ELANSEEVQEFL 666
Cdd:cd06882     66 CTLPTLPgkiyVGR-KAEIAERRIPLLNRYMKELLSLPvWVLMDEDVRLFF 115

The phosphoinositide binding Phox Homology domain of RPK118-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 bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  588 TVNRRYREFLNLQtrleekSDLRKFIKNVKGPKKLFPDLP----FGNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQ 663
Cdd:cd07287     39 VVWKRYSDFKKLH------KDLWQIHKNLCRQSELFPPFAkakvFGRFDESVIEERRQCAEDLLQFSANIPALYNSSQLE 112

                   ...
gi 1768750140  664 EFL 666
Cdd:cd07287    113 DFF 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 1768750140  585 AYH-TVnrRYREFLNLQtrleEKsdLRKFIKNVKG----PKKLFPdlpfgnMDSDRVEARKSLLESFLKQLCAIPELANS 659
Cdd:cd06885     28 VLHcSV--RYSQLHGLN----EQ--LKKEFGNRKLppfpPKKLLP------LTPAQLEERRLQLEKYLQAVVQDPRIANS 93

                   ....*..
gi 1768750140  660 EEVQEFL 666
Cdd:cd06885     94 DIFNSFL 100

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  589 VNRRYREFLNLQTRLEEKSDLrkfikNVKGPKKLFPDLpfgNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQEFLAL 668
Cdd:cd06872     35 VKRRFRNFETLHRRLKEVPKY-----NLELPPKRFLSS---SLDGAFIEERCKLLDKYLKDLLVIEKVAESHEVWSFLSA 106

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gi 1768750140  669 N 669
Cdd:cd06872    107 R 107

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  589 VNRRYREFLNLQTRLEEKSDL-------RKFIknVKGPKKLFPDlpfgnmdsDRVEARKSLLESFLKQLCAIPELANSEE 661
Cdd:cd07284     39 VRRRYQDFLWLKGRLEEAHPTliipplpEKFV--MKGMVERFNE--------DFIETRRKALHKFLNRIADHPTLTFNED 108

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gi 1768750140  662 VQEFL 666
Cdd:cd07284    109 FKIFL 113

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.

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gi 1768750140  548 TIT-AREHSGTgfhpYTLYTVKYETAldgeSSGGLQQLAYHTVNRRYREFLNLQtrlEEKSDLRKFIKnVKGPkklFPDL 626
Cdd:cd06881      6 TVTdTRRHKKG----YTEYKITSKVF----SRSVPEDVSEVVVWKRYSDFKKLH---RELSRLHKQLY-LSGS---FPPF 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1768750140  627 P----FGNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQEF 665
Cdd:cd06881     71 PkgkyFGRFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQF 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768750140  588 TVNRRYREFLNLQTRLEEKSdlrkfiknvkgPKKLFPDLP----FGNMDSDRVEARKSLLESFLKQLCAIPELANSEEVQ 663
Cdd:cd06862     33 TVSRRYKHFDWLYERLVEKY-----------SCIAIPPLPekqvTGRFEEDFIEKRRERLELWMNRLARHPVLSQSEVFR 101

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gi 1768750140  664 EFL 666
Cdd:cd06862    102 HFL 104