The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550 219 NAVLRVPIIGYEVMEERARFTAYKLRVENPEtNDYWLVMRRYTDFVRLNSKLKQAFPNLTLMLPRKKLFGDNFNAVFLDN 298
Cdd:cd07276   1 DRPIRPPILGYEVMEERARFTVYKIRVENKV-GDSWFVFRRYTDFVRLNDKLKQMFPGFRLSLPPKRWFKDNFDPDFLEE 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 24654550 299 RVQGLQIFVNSVMAKEELRKCKLVREFFCLD 329
Cdd:cd07276  80 RQLGLQAFVNNIMAHKDIAKCKLVREFFCLD 110

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550 219 NAVLRVPIIGYEVMEERARFTAYKLRVENPEtNDYWLVMRRYTDFVRLNSKLKQAFPNLTLMLPRKKLFGDNFNAVFLDN 298
Cdd:cd07276   1 DRPIRPPILGYEVMEERARFTVYKIRVENKV-GDSWFVFRRYTDFVRLNDKLKQMFPGFRLSLPPKRWFKDNFDPDFLEE 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 24654550 299 RVQGLQIFVNSVMAKEELRKCKLVREFFCLD 329
Cdd:cd07276  80 RQLGLQAFVNNIMAHKDIAKCKLVREFFCLD 110

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550   246 ENPETNDYWLVMRRYTDFVRLNSKLKQAFPNLTL-MLPRKKLFGdNFNAVFLDNRVQGLQIFVNSVMAKEELRKCKLVRE 324
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIpPLPPKRWLG-RYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLE 79

                  ..
gi 24654550   325 FF 326
Cdd:pfam00787  80 FL 81

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550 219 NAVLRVPIIGYEVMEERARFTAYKLRVENPEtNDYWLVMRRYTDFVRLNSKLKQAFPNLTLMLPRKKLFGDNFNAVFLDN 298
Cdd:cd07276   1 DRPIRPPILGYEVMEERARFTVYKIRVENKV-GDSWFVFRRYTDFVRLNDKLKQMFPGFRLSLPPKRWFKDNFDPDFLEE 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 24654550 299 RVQGLQIFVNSVMAKEELRKCKLVREFFCLD 329
Cdd:cd07276  80 RQLGLQAFVNNIMAHKDIAKCKLVREFFCLD 110

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550 226 IIGYEVMEERAR-FTAYKLRVEnPETNDYWLVMRRYTDFVRLNSKLKQAFPNLTLM-LPRKKLFGdNFNAVFLDNRVQGL 303
Cdd:cd06093   4 IPDYEKVKDGGKkYVVYIIEVT-TQGGEEWTVYRRYSDFEELHEKLKKKFPGVILPpLPPKKLFG-NLDPEFIEERRKQL 81

                        90       100
                ....*....|....*....|....*
gi 24654550 304 QIFVNSVMAKEELRKCKLVREFFCL 328
Cdd:cd06093  82 EQYLQSLLNHPELRNSEELKEFLEL 106

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 24654550    229 YEVMEERARFTAYKLRVENPETndYWLVMRRYTDFVRLNSKLKQAFPNLTL-MLPRKKLFG--DNFNAVFLDNRVQGLQI 305
Cdd:smart00312   5 EKIGDGKHYYYVIEIETKTGLE--EWTVSRRYSDFLELHSKLKKHFPRSILpPLPGKKLFGrlNNFSEEFIEKRRRGLEK 82

                           90       100
                   ....*....|....*....|..
gi 24654550    306 FVNSVM-AKEELRKCKLVREFF 326
Cdd:smart00312  83 YLQSLLnHPELINHSEVVLEFL 104

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 24654550 236 ARFTAYKLRVENPETNDYWLVMR-RYTDFVRLNSKLKQAFPNLTLM----LPRKKLFGD---NFNAVFLDNRVQGLQIFV 307
Cdd:cd07280  20 GAYVVWKITIETKDLIGSSIVAYkRYSEFVQLREALLDEFPRHKRNeipqLPPKVPWYDsrvNLNKAWLEKRRRGLQYFL 99

                        90
                ....*....|....*...
gi 24654550 308 NSVMAKEELRKCKLVREF 325
Cdd:cd07280 100 NCVLLNPVFGGSPVVKEF 117

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 24654550 231 VMEERARFTAYKLRVENPETNDYW--LVMRRYTDFVRLNSKLKQAFPNLT--LMLPRKKLFGdNFNAVFLDNRVQGLQIF 306
Cdd:cd07279  11 VKEGEKKYVVYQLAVVQTGDPDTQpaFIERRYSDFLKLYKALRKQHPQLMakVSFPRKVLMG-NFSSELIAERSRAFEQF 89

                        90       100
                ....*....|....*....|...
gi 24654550 307 VNSVMAKEELRKCKLVREFFCLD 329
Cdd:cd07279  90 LGHILSIPNLRDSKAFLDFLQGP 112

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24654550 256 VMRRYTDFVRLNSKLKQAFPNLTL-MLPRKKLFG-DNFNAVFLDNRVQGLQIFVNSVMAKEELRKCKLVREF 325
Cdd:cd06859  39 VLRRYSDFLWLYERLVEKYPGRIVpPPPEKQAVGrFKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLF 110

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 24654550 223 RVPIIGY--EVMEERARFTAYKLRVENPETNDY---WLVMRRYTDFVRLNSKLKQAFPNL-TLMLPRKKLFGDNF-NAVF 295
Cdd:cd06876  21 RVSIQSYisDVEEEGKEFVVYLIEVQRLNNDDQssgWVVARRYSEFLELHKYLKKRYPGVlKLDFPQKRKISLKYsKTLL 100

                        90       100       110
                ....*....|....*....|....*....|
gi 24654550 296 LDNRVQGLQIFVNSVMAKEELRKCKLVREF 325
Cdd:cd06876 101 VEERRKALEKYLQELLKIPEVCEDEEFRKF 130

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24654550 256 VMRRYTDFVRLNSKLKQAFPNLTL-MLPRKKLF----GDNFNAVFLDNRVQGLQIFVNSVMAKEELRKCKLVREFF 326
Cdd:cd06863  40 VRRRYSDFVFLHECLSNDFPACVVpPLPDKHRLeyitGDRFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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 24654550 238 FTAY----KLRVENPETNDY---WLVMRRYTDFVRLNSKLKQAFPNLTL-MLPRK-------KLFGDNFNAVFLDNRVQG 302
Cdd:cd06864  23 YTVYlietKIVEHESEEGLSkklSSLWRRYSEFELLRNYLVVTYPYVIVpPLPEKramfmwqKLSSDTFDPDFVERRRAG 102

                        90       100
                ....*....|....*....|...
gi 24654550 303 LQIFVNSVMAKEELRKCKLVREF 325
Cdd:cd06864 103 LENFLLRVAGHPELCQDKIFLEF 125

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24654550 256 VMRRYTDFVRLNSKLKQAFPN-LTLMLPRKKL----FGDNFNAVFLDNRVQGLQIFVNSVMAKEELRKCKLVR 323
Cdd:COG5391 175 VRRRYSDFESLHSILIKLLPLcAIPPLPSKKSnseyYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYKNSK 247

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 24654550 224 VPIIGYEVMEErarFTAYKLRVEnpeTNDY-WLVMRRYTDFVRLNSKLKQAFPNLTLMLPRKKLFGDNFNAvFLDNRVQG 302
Cdd:cd06875   6 IRIPSAETVEG---YTVYIIEVK---VGSVeWTVKHRYSDFAELHDKLVAEHKVDKDLLPPKKLIGNKSPS-FVEKRRKE 78

                        90
                ....*....|.
gi 24654550 303 LQIFVNSVMAK 313
Cdd:cd06875  79 LEIYLQTLLSF 89

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; 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. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, 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 24654550 250 TNDYWLVMRRYTDFVRLNSKLKQAFPNLT---LMLPRKKLFGDNFNAvFLDNRVQGLQIFVNSVMAKEELRKCKLVREFF 326
Cdd:cd06878  46 ISSGWVVTRKLSEFHDLHRKLKECSSWLKkveLPSLSKKWFKSIDKK-FLDKSKNQLQKYLQFILEDETLCQSEALYSFL 124

                .
gi 24654550 327 C 327
Cdd:cd06878 125 S 125

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24654550 251 NDYWLVMRRYTDFVRLNSKLKQAFPNL-TLMLPRKKLFGDNFNAVFLDNRVQgLQIFVNSVMA 312
Cdd:cd06874  29 DETWTVFRRYSRFRELHKTMKLKYPEVaALEFPPKKLFGNKSERVAKERRRQ-LETYLRNFFS 90

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550 242 KLRVENPETNDYWlVMRRYTDFVRLNSKLKQAFPNLTL-MLPRK-KLFGDNfnavfldNRVQgLQIFVNSVMAKEELRKC 319
Cdd:cd06869  39 RVRREGEEYRTIY-VARRYSDFKKLHHDLKKEFPGKKLpKLPHKdKLPREK-------LRLS-LRQYLRSLLKDPEVAHS 109

                ....*..
gi 24654550 320 KLVREFF 326
Cdd:cd06869 110 SILQEFL 116

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 24654550 233 EERARFTAYKLRVE-----NPETNDYWLVMRRYTDFVRLNSKLKQAFPNLTL-----MLPRKKLFGdNFNAVFLDNRVQG 302
Cdd:cd06881  12 RHKKGYTEYKITSKvfsrsVPEDVSEVVVWKRYSDFKKLHRELSRLHKQLYLsgsfpPFPKGKYFG-RFDAAVIEERRQA 90

                        90       100
                ....*....|....*....|....
gi 24654550 303 LQIFVNSVMAKEELRKCKLVREFF 326
Cdd:cd06881  91 ILELLDFVGNHPALYQSSAFQQFF 114

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 24654550 231 VMEERARFTAYklrveNPETNDYWLVMRRYTDFVRLNSKLKQAFPNLTL-MLPRKKLFgdNFNAVFLDNRVQGLQIFVNS 309
Cdd:cd06886  14 VEQNGEKFVVY-----NIYMAGRQLCSRRYREFANLHQNLKKEFPDFQFpKLPGKWPF--SLSEQQLDARRRGLEQYLEK 86

                        90
                ....*....|....*.
gi 24654550 310 VMAKEELRKCKLVREF 325
Cdd:cd06886  87 VCSIRVIGESDIMQDF 102

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 24654550 238 FTAYKLRVENPETNdywlVMRRYTDFVRLNSKLKQAFPNLTL-MLPRKKLFGdNFNAVFLDNRVQGLQIFVNSVMAKEEL 316
Cdd:cd06862  20 FIAYQITPTHTNVT----VSRRYKHFDWLYERLVEKYSCIAIpPLPEKQVTG-RFEEDFIEKRRERLELWMNRLARHPVL 94

                        90
                ....*....|....*
gi 24654550 317 RKCKLVREFF-CLDE 330
Cdd:cd06862  95 SQSEVFRHFLtCTDE 109

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24654550 235 RARFTAYKLRV-------ENPETNdywlVMRRYTDFVRLNSKLKQAFPNLTLMLPRKKLF------GDN--FNAVFLDNR 299
Cdd:cd06894  16 KKRFTDYEVRMrtnlpvfKKKESS----VRRRYSDFEWLRSELERDSKIVVPPLPGKALKrqlpfrGDDgiFEEEFIEER 91

                        90
                ....*....|.
gi 24654550 300 VQGLQIFVNSV 310
Cdd:cd06894  92 RKGLETFINKV 102