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 442625556  65 LRFDILLAHIMPPDGedvkiKRFVVYELTVKQDGaTEDTQPAKIERRYTDFRELYLGLKRQHPAEMANKYFPAKVLMGNF 144
Cdd:cd07279    1 LKFEIVSARTVKEGE-----KKYVVYQLAVVQTG-DPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNF 74

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442625556 145 KSELIGERSAAFEAFLTYVASQAMLRDSEYFLRFLQHD 182
Cdd:cd07279   75 SSELIAERSRAFEQFLGHILSIPNLRDSKAFLDFLQGP 112

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 442625556  65 LRFDILLAHIMPPDGedvkiKRFVVYELTVKQDGaTEDTQPAKIERRYTDFRELYLGLKRQHPAEMANKYFPAKVLMGNF 144
Cdd:cd07279    1 LKFEIVSARTVKEGE-----KKYVVYQLAVVQTG-DPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNF 74

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442625556 145 KSELIGERSAAFEAFLTYVASQAMLRDSEYFLRFLQHD 182
Cdd:cd07279   75 SSELIAERSRAFEQFLGHILSIPNLRDSKAFLDFLQGP 112

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 442625556    83 KIKRFVVYELTVKQDgatedTQPAKIERRYTDFRELYLGLKRQHPAEMANkYFPAKVLMG---NFKSELIGERSAAFEAF 159
Cdd:smart00312  10 GKHYYYVIEIETKTG-----LEEWTVSRRYSDFLELHSKLKKHFPRSILP-PLPGKKLFGrlnNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|..
gi 442625556   160 LTYVASQAML-RDSEYFLRFLQ 180
Cdd:smart00312  84 LQSLLNHPELiNHSEVVLEFLE 105

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 442625556  65 LRFDILLAHIMPPDGedvkiKRFVVYELTVKQDGaTEDTQPAKIERRYTDFRELYLGLKRQHPAEMANKYFPAKVLMGNF 144
Cdd:cd07279    1 LKFEIVSARTVKEGE-----KKYVVYQLAVVQTG-DPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNF 74

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442625556 145 KSELIGERSAAFEAFLTYVASQAMLRDSEYFLRFLQHD 182
Cdd:cd07279   75 SSELIAERSRAFEQFLGHILSIPNLRDSKAFLDFLQGP 112

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; 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. 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. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442625556  65 LRFDILLAHImppdgEDVKIKRFVVYELTVKQDGATeDTQPAKIERRYTDFRELYLGLKRQHPAEMANKYFPAKVLMGNF 144
Cdd:cd07300    1 LLFEIPSARI-----IEQTISKHVVYQIIVIQTGSF-DCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNF 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 442625556 145 KSELIGERSAAFEAFLTYVASQAMLRDSEYFLRFLQHDEL 184
Cdd:cd07300   75 SEEIIAERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

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 442625556  83 KIKRFVVYELTVKQDGATEDTqpakIERRYTDFRELYLGLKRQHPAEMANKyFPAKVLMGNFKSELIGERSAAFEAFLTY 162
Cdd:cd06093   13 GGKKYVVYIIEVTTQGGEEWT----VYRRYSDFEELHEKLKKKFPGVILPP-LPPKKLFGNLDPEFIEERRKQLEQYLQS 87

                         90
                 ....*....|....*...
gi 442625556 163 VASQAMLRDSEYFLRFLQ 180
Cdd:cd06093   88 LLNHPELRNSEELKEFLE 105

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 442625556  85 KRFVVYELTVKQDGatEDTQPA--KIERRYTDFRELYLGLKRQHPAEMANKyFPAKVLMG--NFKSELIGERSAAFEAFL 160
Cdd:cd06876   36 KEFVVYLIEVQRLN--NDDQSSgwVVARRYSEFLELHKYLKKRYPGVLKLD-FPQKRKISlkYSKTLLVEERRKALEKYL 112

                         90       100
                 ....*....|....*....|....
gi 442625556 161 tyvasQAMLR-----DSEYFLRFL 179
Cdd:cd06876  113 -----QELLKipevcEDEEFRKFL 131

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442625556  88 VVYELTVKQDGATEDTQPAKIERRYTDFRELYLGLKRQHPAEMANKyFPAKVLMGNFKSELIGERSAAFEAFLTYVASQA 167
Cdd:cd06861   19 TVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPP-PPEKQSVGRFDDNFVEQRRAALEKMLRKIANHP 97

                         90
                 ....*....|....*
gi 442625556 168 MLRDSEYFLRFLQHD 182
Cdd:cd06861   98 VLQKDPDFRLFLESE 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 442625556  87 FVVYELTVKQDGATEDTQPAKIERRYTDFRELYLGLKRQHPAEMA----NKYFPAKVLMGNFKSELIGERSAAFEAFLTY 162
Cdd:cd06863   19 YISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDFPACVVpplpDKHRLEYITGDRFSPEFITRRAQSLQRFLRR 98

                         90
                 ....*....|....*..
gi 442625556 163 VASQAMLRDSEYFLRFL 179
Cdd:cd06863   99 ISLHPVLSQSKILHQFL 115

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 442625556  82 VKIKRFVVYELTVKQDGATedtqpAKIERRYTDFRELYLGLKRQHPAEMANKyFPAK--VLMGNFKSELIGERSAAFEAF 159
Cdd:cd06897   10 VSPKPYTVYNIQVRLPLRS-----YTVSRRYSEFVALHKQLESEVGIEPPYP-LPPKswFLSTSSNPKLVEERRVGLEAF 83

                         90       100
                 ....*....|....*....|...
gi 442625556 160 LT--YVASQAMLRDSEYFLRFLQ 180
Cdd:cd06897   84 LRalLNDEDSRWRNSPAVKEFLN 106

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442625556  85 KRFVVYELT---VKQDGAtEDTQPAKIERRYTDFRELYLGLKRQHpAEMANK----YFPAKVLMGNFKSELIGERSAAFE 157
Cdd:cd06881   15 KGYTEYKITskvFSRSVP-EDVSEVVVWKRYSDFKKLHRELSRLH-KQLYLSgsfpPFPKGKYFGRFDAAVIEERRQAIL 92

                         90       100
                 ....*....|....*....|....*
gi 442625556 158 AFLTYVASQAMLRDSEYFLRFLQHD 182
Cdd:cd06881   93 ELLDFVGNHPALYQSSAFQQFFEEA 117

The phosphoinositide binding Phox Homology domain of Sorting Nexin 7; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX7 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, SNX30, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX7 has yet to be elucidated.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442625556  77 PDGEDVKIKRFVVYELTVKQDGATEDTQPAKIERRYTDFRELYLGLKRQHPAEMAN---KYFPAKVLMGNFKSELIGERS 153
Cdd:cd07284    8 PESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPplpEKFVMKGMVERFNEDFIETRR 87

                         90       100
                 ....*....|....*....|....*.
gi 442625556 154 AAFEAFLTYVASQAMLRDSEYFLRFL 179
Cdd:cd07284   88 KALHKFLNRIADHPTLTFNEDFKIFL 113

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 442625556  74 IMPPDGEDVKIKRFVVYELTVKQDGATEDTQPAKIERRYTDFRELYLGLKRQH-------PAEMANKYFPAKVLMGNFKS 146
Cdd:cd07294    8 IFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSkivvpplPGKALKRQLPFRGDEGIFEE 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 442625556 147 ELIGERSAAFEAFLTYVASQAMLRDSEYFLRFLQHDELTR 186
Cdd:cd07294   88 SFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDETIDR 127

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 442625556  87 FVVYEL-TVKQDGATEDTQPAKIE---RRYTDFREL--YLGLKRQH------PAEMANkYFPAKVLMGNFKSELIGERSA 154
Cdd:cd06864   23 YTVYLIeTKIVEHESEEGLSKKLSslwRRYSEFELLrnYLVVTYPYvivpplPEKRAM-FMWQKLSSDTFDPDFVERRRA 101

                         90       100
                 ....*....|....*....|....*..
gi 442625556 155 AFEAFLTYVASQAMLRDSEYFLRFLQH 181
Cdd:cd06864  102 GLENFLLRVAGHPELCQDKIFLEFLTH 128

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal 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. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 442625556 108 IERRYTDFRELYLGLKRQHPAEMANKyFPAKVLMGNFKSELIGER 152
Cdd:cd07277   34 VYRRYSEFYELHKKLKKKFPVVRSFD-FPPKKAIGNKDAKFVEER 77

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 442625556  80 EDVKIKRFVVYELTVKQ---DGATEDTQPAKIERRYTDFRELYLGLKRQHpAEMANKYFPAKVLMGNFKSELIGERSAAF 156
Cdd:cd06877   15 DPSNGERIYVFCIEVERndrRAKGHEPQHWSVLRRYNEFYVLESKLTEFH-GEFPDAPLPSRRIFGPKSYEFLESKREIF 93

                         90       100
                 ....*....|....*....|....*.
gi 442625556 157 EAFLTYVASQAMLRDSEYFLRFLQHD 182
Cdd:cd06877   94 EEFLQKLLQKPELRGSELLYDFLSPN 119

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442625556 107 KIERRYTDFRELYLGLK---RQHPaemankyFPAKVLMGNFKSELIGERSAAFEAFLTYVASQAMLRDSEYFLRFL 179
Cdd:cd06871   39 QVIRRYNDFDLLNASLQisgISLP-------LPPKKLIGNMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

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 442625556  67 FDILLAHimPPDGEDV-KIKRFVVYELTvkqdgATEDTQPakIERRYTDFRELYLGLKRQHPAEMANKYFPAKVLMGNFK 145
Cdd:cd07285    1 FDCVVAD--PRKGSKMyGLKSYIEYQLT-----PTNTNRS--VNHRYKHFDWLYERLLVKFGLAIPIPSLPDKQVTGRFE 71

                         90       100       110
                 ....*....|....*....|....*....|....
gi 442625556 146 SELIGERSAAFEAFLTYVASQAMLRDSEYFLRFL 179
Cdd:cd07285   72 EEFIKMRMERLQAWMTRMCRHPVISESEVFQQFL 105

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 442625556  84 IKRFVVYELTVKQDGATedtqpakIERRYTDFRELYLGLKRQHPAEMANKyFPAKVLMGNFKSELIGERSAAFEAFLTYV 163
Cdd:cd06866   15 FLKHVEYEVSSKRFKST-------VYRRYSDFVWLHEYLLKRYPYRMVPA-LPPKRIGGSADREFLEARRRGLSRFLNLV 86

                         90
                 ....*....|....*...
gi 442625556 164 ASQAMLRDSE---YFLRF 178
Cdd:cd06866   87 ARHPVLSEDElvrTFLTE 104