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 46370089   9 FLRHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEFPAFPRAQVFGRF 88
Cdd:cd07288   1 YYRFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRF 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 46370089  89 EASVIEERRKGAEDLLRFTVHIPALNNSPQLKEFFRGG 126
Cdd:cd07288  81 EAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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 46370089   9 FLRHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEFPAFPRAQVFGRF 88
Cdd:cd07288   1 YYRFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRF 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 46370089  89 EASVIEERRKGAEDLLRFTVHIPALNNSPQLKEFFRGG 126
Cdd:cd07288  81 EAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

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 46370089     15 VSDPRTHpkGYTEYKVTAQFISKKDPEdvKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGR---FEAS 91
Cdd:smart00312   1 VVEPEKI--GDGKHYYYVIEIETKTGL--EEWTVSRRYSDFLELHSKLKKHFPRSI-----LPPLPGKKLFGRlnnFSEE 71

                           90       100       110
                   ....*....|....*....|....*....|...
gi 46370089     92 VIEERRKGAEDLLRFTVHIPAL-NNSPQLKEFF 123
Cdd:smart00312  72 FIEKRRRGLEKYLQSLLNHPELiNHSEVVLEFL 104

Microtubule Interacting and Trafficking molecule domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46370089    182 AQEALDLLFNCESTEEASGSP-ARGPLTEAELALFDPFSKEgdPLPARQEGVKKKAAEYLKRAEEILRLHLSQLP 255
Cdd:smart00745   5 LSKAKELISKALKADEAGNYEeALELYKKAIEYLLEGIKVE--SDSKRREALKAKAAEYLDRAEEIKKSLLERLA 77

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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 46370089   9 FLRHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEFPAFPRAQVFGRF 88
Cdd:cd07288   1 YYRFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRF 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 46370089  89 EASVIEERRKGAEDLLRFTVHIPALNNSPQLKEFFRGG 126
Cdd:cd07288  81 EAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

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 46370089  11 RHYTVSDPRTHPKGYTEYKVTAQFISKKDPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFRRlEEFPAFPRAQVFGRFEA 90
Cdd:cd06881   3 RSFTVTDTRRHKKGYTEYKITSKVFSRSVPEDVSEVVVWKRYSDFKKLHRELSRLHKQLYLS-GSFPPFPKGKYFGRFDA 81

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 46370089  91 SVIEERRKGAEDLLRFTVHIPALNNSPQLKEFFRGG 126
Cdd:cd06881  82 AVIEERRQAILELLDFVGNHPALYQSSAFQQFFEEA 117

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 46370089  14 TVSDPRTHP---KGYTEYKVTAQfiskkdPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGRFEA 90
Cdd:cd06093   3 SIPDYEKVKdggKKYVVYIIEVT------TQGGEEWTVYRRYSDFEELHEKLKKKFPGVI-----LPPLPPKKLFGNLDP 71

                        90       100       110
                ....*....|....*....|....*....|....
gi 46370089  91 SVIEERRKGAEDLLRFTVHIPALNNSPQLKEFFR 124
Cdd:cd06093  72 EFIEERRKQLEQYLQSLLNHPELRNSEELKEFLE 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 46370089  19 RTHPKGYTEYKVTAQFISKKDPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEefpaFPRAQVFGRFEASVIEERRK 98
Cdd:cd07279   9 RTVKEGEKKYVVYQLAVVQTGDPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVS----FPRKVLMGNFSSELIAERSR 84

                        90       100
                ....*....|....*....|....*..
gi 46370089  99 GAEDLLRFTVHIPALNNSPQLKEFFRG 125
Cdd:cd07279  85 AFEQFLGHILSIPNLRDSKAFLDFLQG 111

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 46370089  14 TVSDPRT---HPKGYTEYKVTAQfISKKDPEdVKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFPRAQVFGRFEA 90
Cdd:cd06861   4 TVGDPHKvgdLTSAHTVYTVRTR-TTSPNFE-VSSFSVLRRYRDFRWLYRQLQNNHPGVI-----VPPPPEKQSVGRFDD 76

                        90       100       110
                ....*....|....*....|....*....|..
gi 46370089  91 SVIEERRKGAEDLLRFTVHIPALNNSPQLKEF 122
Cdd:cd06861  77 NFVEQRRAALEKMLRKIANHPVLQKDPDFRLF 108

Microtubule Interacting and Trafficking molecule domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46370089    182 AQEALDLLFNCESTEEASGSP-ARGPLTEAELALFDPFSKEgdPLPARQEGVKKKAAEYLKRAEEILRLHLSQLP 255
Cdd:smart00745   5 LSKAKELISKALKADEAGNYEeALELYKKAIEYLLEGIKVE--SDSKRREALKAKAAEYLDRAEEIKKSLLERLA 77

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46370089  14 TVSDPRTHP---------KGYTEYKVTAQfiSKKDPEDVKEVVVWKRYSDFRKLHGDLAYTHRNLFrrleeFPAFP---- 80
Cdd:cd06865   3 TVSDPKKEQepsrvplggPPYISYKVTTR--TNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAF-----VPPRPdksv 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 46370089  81 -RAQVFGRFEasVIEERRKGAEDLLRFTVHIPALNNSPQLKEFFR 124
Cdd:cd06865  76 vESQVMQSAE--FIEQRRVALEKYLNRLAAHPVIGLSDELRVFLT 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX2 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46370089  15 VSDPRTHPKG---YTEYKVTAQfiSKKDPEDVKEVVVWKRYSDFRKLHGDLA--YTHRNLFrrleeFPAFPRAQVFGRFE 89
Cdd:cd07282   5 VSDPEKVGDGmnaYMAYRVTTK--TSLSMFSRSEFSVRRRFSDFLGLHSKLAskYLHVGYI-----VPPAPEKSIVGMTK 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 46370089  90 ASV----------IEERRKGAEDLLRFTVHIPALNNSPQLKEFF 123
Cdd:cd07282  78 VKVgkedssstefVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 121

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 46370089   4 QAKDDFLRHYTVSDPRTHPKGYTEYKVTAQFIskkdPEDVKEVVVWKRYSDFRKLHGDLaythrnlfrrLEEFPAFPRAQ 83
Cdd:cd07280   1 HATDVNVGDYTIVGGDTGGGAYVVWKITIETK----DLIGSSIVAYKRYSEFVQLREAL----------LDEFPRHKRNE 66

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 46370089  84 V------------FGRFEASVIEERRKGAEdllRFTVHI---PALNNSPQLKEF 122
Cdd:cd07280  67 IpqlppkvpwydsRVNLNKAWLEKRRRGLQ---YFLNCVllnPVFGGSPVVKEF 117

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 46370089  14 TVSDPRTHPKGYTEYKVTAQFIskkdpedVKEVVVWKRYSDFRKLHGDLAY-THRNlfrRLEEFPafPRAQVFGRF-EAS 91
Cdd:cd06897   4 SIPTTSVSPKPYTVYNIQVRLP-------LRSYTVSRRYSEFVALHKQLESeVGIE---PPYPLP--PKSWFLSTSsNPK 71

                        90       100       110
                ....*....|....*....|....*....|...
gi 46370089  92 VIEERRKGAEDLLRFTVHIP--ALNNSPQLKEF 122
Cdd:cd06897  72 LVEERRVGLEAFLRALLNDEdsRWRNSPAVKEF 104

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 46370089  21 HPKG----YTEYKVTAQFISKKdpedvkevvVWKRYSDFRKLHGDLayTHRNLFRRLeefPAFPRAQVFGRFEASVIEER 96
Cdd:cd06866  10 EKKGlflkHVEYEVSSKRFKST---------VYRRYSDFVWLHEYL--LKRYPYRMV---PALPPKRIGGSADREFLEAR 75

                        90       100
                ....*....|....*....|....*...
gi 46370089  97 RKGAEDLLRFTVHIPALNNSPQLKEFFR 124
Cdd:cd06866  76 RRGLSRFLNLVARHPVLSEDELVRTFLT 103

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46370089  20 THPkgYTEYKVTAQFISKKDPE---------DVKEVVVWKRYSDFRKLHGDLayTHRNLFRRL-------EEFPAFPraq 83
Cdd:cd06893  18 THP--YTLYTVQYETILDVQSEqnpnaaseqPLATHTVNRRFREFLTLQTRL--EENPKFRKImnvkgppKRLFDLP--- 90

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 46370089  84 vFGRFEASVIEERRKGAEDLLRFTVHIPALNNSPQLKEF 122
Cdd:cd06893  91 -FGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEF 128

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46370089  23 KGYTEYKVTAQFiskkdpeDVKEVVVWKRYSDFRKLHGDLAythrnlfrrlEEFPA----FPRAQVFGR-FEASVIEERR 97
Cdd:cd06870  18 KRFTVYKVVVSV-------GRSSWFVFRRYAEFDKLYESLK----------KQFPAsnlkIPGKRLFGNnFDPDFIKQRR 80

                        90       100
                ....*....|....*....|....*.
gi 46370089  98 KGAEDLLRFTVHIPALNNSPQLKEFF 123
Cdd:cd06870  81 AGLDEFIQRLVSDPKLLNHPDVRAFL 106

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 46370089  48 VWKRYSDFRKLHGDLaythRNLFRRLEEFpAFPRAQVFGRFEASVIEERRKGAEDLLR 105
Cdd:cd07277  34 VYRRYSEFYELHKKL----KKKFPVVRSF-DFPPKKAIGNKDAKFVEERRKRLQVYLR 86

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46370089  15 VSDPRTHPKG---YTEYKV---TAQFISKKdpedvKEVVVWKRYSDFRKLHGDLAYTHRNLFRRLEEfPAFPRAQVF--- 85
Cdd:cd06894   6 VVNPQTHGVGkkrFTDYEVrmrTNLPVFKK-----KESSVRRRYSDFEWLRSELERDSKIVVPPLPG-KALKRQLPFrgd 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 46370089  86 -GRFEASVIEERRKGAEDLLRFTVHIPALNNSPQLKEF 122
Cdd:cd06894  80 dGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMF 117

MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar sorting proteins and others. The molecular function of the MIT domain is unclear.

                        10        20        30
                ....*....|....*....|....*....|...
gi 46370089 222 GDPLPARQEGVKKKAAEYLKRAEEILRLHLSQL 254
Cdd:cd02656  42 AEKEPKLRKLLRKKVKEYLDRAEFLKELLKKQK 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46370089  47 VVWKRYSDFRKLHGDLaythRNLFRRLEEfpAFPRAQVFG-RFEASVIEERRKGAEDLLRFTVHIPALNNSPQLKEFF 123
Cdd:cd07276  36 FVFRRYTDFVRLNDKL----KQMFPGFRL--SLPPKRWFKdNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFF 107