The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767935784   1 MEVYIPSFRYEESDLERGYTvvivwhrafqtkmesyevivleiafsngrltyqVFKIEVLMNGRKHFVEKRYSEFHALHK 80
Cdd:cd06880    1 IEVSIPSYRLEVDESEKPYT---------------------------------VFTIEVLVNGRRHTVEKRYSEFHALHK 47

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767935784  81 KLKKCIKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAVILENeELPKLFLDFLNVRHLPSLPKA 144
Cdd:cd06880   48 KLKKSIKTPDFPPKRVRNWNPKVLEQRRQGLEAYLQGLLKIN-ELPKQLLDFLGVRHFPSLPKS 110

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767935784   1 MEVYIPSFRYEESDLERGYTvvivwhrafqtkmesyevivleiafsngrltyqVFKIEVLMNGRKHFVEKRYSEFHALHK 80
Cdd:cd06880    1 IEVSIPSYRLEVDESEKPYT---------------------------------VFTIEVLVNGRRHTVEKRYSEFHALHK 47

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767935784  81 KLKKCIKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAVILENeELPKLFLDFLNVRHLPSLPKA 144
Cdd:cd06880   48 KLKKSIKTPDFPPKRVRNWNPKVLEQRRQGLEAYLQGLLKIN-ELPKQLLDFLGVRHFPSLPKS 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 767935784    39 IVLEIAFSNGRLTYQVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHV----RNWVPKVLEQRRQGL 111
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRsilPPLPGKKLfgrlNNFSEEFIEKRRRGL 80

                           90       100
                   ....*....|....*....|....*.
gi 767935784   112 ETYLQAvILENEELP---KLFLDFLN 134
Cdd:smart00312  81 EKYLQS-LLNHPELInhsEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767935784   1 MEVYIPSFRYEESDLERGYTvvivwhrafqtkmesyevivleiafsngrltyqVFKIEVLMNGRKHFVEKRYSEFHALHK 80
Cdd:cd06880    1 IEVSIPSYRLEVDESEKPYT---------------------------------VFTIEVLVNGRRHTVEKRYSEFHALHK 47

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767935784  81 KLKKCIKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAVILENeELPKLFLDFLNVRHLPSLPKA 144
Cdd:cd06880   48 KLKKSIKTPDFPPKRVRNWNPKVLEQRRQGLEAYLQGLLKIN-ELPKQLLDFLGVRHFPSLPKS 110

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 767935784  51 TYQVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKTP---EIPSKHvRNWV----PKVLEQRRQGLETYLQAvILENE 123
Cdd:cd06897   14 PYTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEppyPLPPKS-WFLStssnPKLVEERRVGLEAFLRA-LLNDE 91

                         90
                 ....*....|....*..
gi 767935784 124 ELP----KLFLDFLNVR 136
Cdd:cd06897   92 DSRwrnsPAVKEFLNLP 108

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 767935784    39 IVLEIAFSNGRLTYQVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHV----RNWVPKVLEQRRQGL 111
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRsilPPLPGKKLfgrlNNFSEEFIEKRRRGL 80

                           90       100
                   ....*....|....*....|....*.
gi 767935784   112 ETYLQAvILENEELP---KLFLDFLN 134
Cdd:smart00312  81 EKYLQS-LLNHPELInhsEVVLEFLE 105

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 767935784  51 TYQVFKIEVLMNGRKHFVEKRYSEFHALHKKL---KKCIKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAV-ILENEELP 126
Cdd:cd06875   16 GYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLvaeHKVDKDLLPPKKLIGNKSPSFVEKRRKELEIYLQTLlSFFQKTMP 95

                 ....*..
gi 767935784 127 KLFLDFL 133
Cdd:cd06875   96 RELAHFL 102

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767935784  46 SNGRLTYQVFkieVLMNGRKHFVEKRYSEFHALHKKLKKciKTPEI------PSKHVRNWVPKVLEQRRQGLETYLQAVI 119
Cdd:cd07277   15 SDAHHVYQVY---IRIRDDEWNVYRRYSEFYELHKKLKK--KFPVVrsfdfpPKKAIGNKDAKFVEERRKRLQVYLRRVV 89

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767935784  70 KRYSEFHALHKKLKKCIKT------PEIPSKhvRNWV-------PKVLEQRRQGLETYLQAVIL 120
Cdd:cd07280   43 KRYSEFVQLREALLDEFPRhkrneiPQLPPK--VPWYdsrvnlnKAWLEKRRRGLQYFLNCVLL 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767935784  68 VEKRYSEFHALHKKLKKC-IKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAV----ILENEELPKLFLD 131
Cdd:cd06871   40 VIRRYNDFDLLNASLQISgISLPLPPKKLIGNMDREFIAERQQGLQNYLNVIlmnpILASCLPVKKFLD 108

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 767935784  68 VEKRYSEFHALHKKLKKC---IKTPEIPSKH-VRNWVPKV--LEQRRQGLETYLQAV----ILENEELPKLFL 130
Cdd:cd06859   39 VLRRYSDFLWLYERLVEKypgRIVPPPPEKQaVGRFKVKFefIEKRRAALERFLRRIaahpVLRKDPDFRLFL 111

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 767935784  52 YQVFKIEVLMNGRKHF-----VEKRYSEFHALHKKLKKciKTPEI-----PSKHV---RNWVPKVLEQRRQGLETYLQAV 118
Cdd:cd06876   38 FVVYLIEVQRLNNDDQssgwvVARRYSEFLELHKYLKK--RYPGVlkldfPQKRKislKYSKTLLVEERRKALEKYLQEL 115

                 ..
gi 767935784 119 IL 120
Cdd:cd06876  116 LK 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767935784  67 FVEKRYSEFHALHKKLKK----CIKTPEIPSKH-VRNWVPKVLEQRRQGLETYLQaVILENEEL--PKLFLDFL 133
Cdd:cd07279   37 FIERRYSDFLKLYKALRKqhpqLMAKVSFPRKVlMGNFSSELIAERSRAFEQFLG-HILSIPNLrdSKAFLDFL 109

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767935784  48 GRLTYQVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKC---IKTPEIPSKHV-RNWVPKVLEQRRQGLETYLQAVI 119
Cdd:cd06874   14 GKDEHFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKypeVAALEFPPKKLfGNKSERVAKERRRQLETYLRNFF 89

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767935784  52 YQVFKIEVLMNGRKH--FVEKRYSEFHALHKKLKK---CIKTPEIPSKHV--RNWVPKVLEQRRQGLETYLQAVILENEE 124
Cdd:cd06883   16 YYIYVVKVTRENQTEpsFVFRTFEEFQELHNKLSLlfpSLKLPSFPARVVlgRSHIKQVAERRKIELNSYLKSLFNASPE 95

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 767935784  48 GRLTYQVFKIEV-LMNGRKHFVEKRYSEFHALHKKL------------KKCIkTPEIPSKHVRNWVPKVLEQRRQGLETY 114
Cdd:cd06882   16 GFTNYYVFVIEVkTKGGSKYLIYRRYRQFFALQSKLeerfgpeagssaYDCT-LPTLPGKIYVGRKAEIAERRIPLLNRY 94

                 ..
gi 767935784 115 LQ 116
Cdd:cd06882   95 MK 96

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 767935784  52 YQVFKIEVLMNG----RKHFVEKRYSEFHALHKKLKKC----IKTPEIPSKHV-RNWVPKVLEQRRQGLETYL-QAVILE 121
Cdd:cd07300   18 HVVYQIIVIQTGsfdcNKVVIERRYSDFLKLHQELLSDfseeLEDVVFPKKKLtGNFSEEIIAERRVALRDYLtLLYSLR 97

                         90
                 ....*....|..
gi 767935784 122 NEELPKLFLDFL 133
Cdd:cd07300   98 FVRRSQAFQDFL 109

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 767935784  41 LEIAFSN------GRLTYQVFKIEVLMNG-----RKHFVEKRYSEFHALHKKLKKCIKT--PEIPSKHVRNWVP------ 101
Cdd:cd07293    2 LEIDVTNpqtvgvGRGRFTTYEIRLKTNLpifklKESTVRRRYSDFEWLRSELERESKVvvPPLPGKALFRQLPfrgddg 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 767935784 102 ----KVLEQRRQGLETYLQAV----ILENEELPKLFL 130
Cdd:cd07293   82 ifddSFIEERKQGLEQFLNKVaghpLAQNERCLHMFL 118

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 767935784  46 SNGRlTYQVFKIEVLMNGR-------KHF-VEKRYSEFHALHKKLKK---CIKTPEIPSKhvRNWVPKV---LEQRRQGL 111
Cdd:cd06877   17 SNGE-RIYVFCIEVERNDRrakghepQHWsVLRRYNEFYVLESKLTEfhgEFPDAPLPSR--RIFGPKSyefLESKREIF 93

                         90       100
                 ....*....|....*....|...
gi 767935784 112 ETYLQAV----ILENEELPKLFL 130
Cdd:cd06877   94 EEFLQKLlqkpELRGSELLYDFL 116