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 568996463 304 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ 383
Cdd:cd07277    1 INVWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKR 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568996463 384 LQSYLRSVMNKVIQMVPEFAANPKKETLVQLVPFFVDI 421
Cdd:cd07277   81 LQVYLRRVVNTLIQTSPELTACPSKETLIKLLPFFGDT 118

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463   114 ELRQAIVAMMNRKDELEEENGSLRNLLDGEMEHSAALRQEVDALRRKVTEQQE---RHATKVQALARENEVLKVQLKKYv 190
Cdd:TIGR02168  681 ELEEKIEELEEKIAELEKALAELRKELEELEEELEQLRKELEELSRQISALRKdlaRLEAEVEQLEERIAQLSKELTEL- 759

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463   191 gAVQMLKREGQTAEAVPSLWNVDAEVTVPEQKPGEVAEELASSYERklieVAEMHGELIEFNERLHRALVAKEALVSQMR 270
Cdd:TIGR02168  760 -EAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREA----LDELRAELTLLNEEAANLRERLESLERRIA 834

                          170       180
                   ....*....|....*....|....
gi 568996463   271 QELIDLRgpvpgDLSQTSEDQSLS 294
Cdd:TIGR02168  835 ATERRLE-----DLEEQIEELSED 853

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 568996463 304 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ 383
Cdd:cd07277    1 INVWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKR 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568996463 384 LQSYLRSVMNKVIQMVPEFAANPKKETLVQLVPFFVDI 421
Cdd:cd07277   81 LQVYLRRVVNTLIQTSPELTACPSKETLIKLLPFFGDT 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568996463   319 NAFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIG---NKDAKFVEERRKQLQSYLRSVMN 393
Cdd:smart00312  12 HYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463   114 ELRQAIVAMMNRKDELEEENGSLRNLLDGEMEHSAALRQEVDALRRKVTEQQE---RHATKVQALARENEVLKVQLKKYv 190
Cdd:TIGR02168  681 ELEEKIEELEEKIAELEKALAELRKELEELEEELEQLRKELEELSRQISALRKdlaRLEAEVEQLEERIAQLSKELTEL- 759

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463   191 gAVQMLKREGQTAEAVPSLWNVDAEVTVPEQKPGEVAEELASSYERklieVAEMHGELIEFNERLHRALVAKEALVSQMR 270
Cdd:TIGR02168  760 -EAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREA----LDELRAELTLLNEEAANLRERLESLERRIA 834

                          170       180
                   ....*....|....*....|....
gi 568996463   271 QELIDLRgpvpgDLSQTSEDQSLS 294
Cdd:TIGR02168  835 ATERRLE-----DLEEQIEELSED 853

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 568996463 304 INVWIPSVFLRGKAANAFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ 383
Cdd:cd07277    1 INVWIPSVFLRGKGSDAHHVYQVYIRIRDDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKR 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568996463 384 LQSYLRSVMNKVIQMVPEFAANPKKETLVQLVPFFVDI 421
Cdd:cd07277   81 LQVYLRRVVNTLIQTSPELTACPSKETLIKLLPFFGDT 118

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 568996463 305 NVWIPSVFLRGKAANAFHVYQVYIRIKD-DEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ 383
Cdd:cd06093    1 SVSIPDYEKVKDGGKKYVVYIIEVTTQGgEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEFIEERRKQ 80

                         90
                 ....*....|
gi 568996463 384 LQSYLRSVMN 393
Cdd:cd06093   81 LEQYLQSLLN 90

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568996463   319 NAFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIG---NKDAKFVEERRKQLQSYLRSVMN 393
Cdd:smart00312  12 HYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89

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 568996463 308 IPSVFLRGKAanaFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAI--GNKDAKFVEERRKQLQ 385
Cdd:cd06897    5 IPTTSVSPKP---YTVYNIQVRLPLRSYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFlsTSSNPKLVEERRVGLE 81

                 ....*...
gi 568996463 386 SYLRSVMN 393
Cdd:cd06897   82 AFLRALLN 89

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 568996463 321 FHVYQVYIRIK-DDEWNVYRRYTEFRALHHQLQSAFPQVRaYSFPPKKAIG-NKDAKFVEERRKQLQSYLRSVM 392
Cdd:cd07276   20 FTVYKIRVENKvGDSWFVFRRYTDFVRLNDKLKQMFPGFR-LSLPPKRWFKdNFDPDFLEERQLGLQAFVNNIM 92

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 568996463 331 KDDEWNVYRRYTEFRALHHQLQSAfpqVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLRSVM 392
Cdd:cd06871   34 PENSWQVIRRYNDFDLLNASLQIS---GISLPLPPKKLIGNMDREFIAERQQGLQNYLNVIL 92

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 568996463 315 GKAANAFHVYQVYIRIKD-----DEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLR 389
Cdd:cd06861   12 GDLTSAHTVYTVRTRTTSpnfevSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNFVEQRRAALEKMLR 91

                         90
                 ....*....|....
gi 568996463 390 SVMNK-VIQMVPEF 402
Cdd:cd06861   92 KIANHpVLQKDPDF 105

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463 315 GKAANAFHVYQVYIR-----IKDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAK--FVEERRKQLQSY 387
Cdd:cd06859   12 GDGMSAYVVYRVTTKtnlpdFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVKfeFIEKRRAALERF 91

                 ....*.
gi 568996463 388 LRSVMN 393
Cdd:cd06859   92 LRRIAA 97

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 568996463 321 FHVYQVYIRIKDDEW---------NVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKA--------IGNKDAKFVEERRKQ 383
Cdd:cd06864   23 YTVYLIETKIVEHESeeglskklsSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAmfmwqklsSDTFDPDFVERRRAG 102

                 ....*...
gi 568996463 384 LQSYLRSV 391
Cdd:cd06864  103 LENFLLRV 110

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568996463 322 HVYQVYIRIKDDEwnVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLRSVMN 393
Cdd:cd06866   19 VEYEVSSKRFKST--VYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSADREFLEARRRGLSRFLNLVAR 88

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform 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. 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. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. 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 568996463 310 SVFLRGKAANAFHVYQVYIRI----KDDEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRK-QL 384
Cdd:cd07289    3 SVFTYHKRYNPDKHYIYVVRIlregQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKvEL 82

                 ....*....
gi 568996463 385 QSYLRSVMN 393
Cdd:cd07289   83 NSYIQSLMN 91

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568996463 336 NVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGN-KDAKFVEERRKQLQSYLRSVM 392
Cdd:cd06898   38 CVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRfNNEGFIEERQQGLQDFLEKVL 95

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 568996463 305 NVWIPSV-FLRGKAANafHVYQVYI--------RIKDDE---WNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNK 372
Cdd:cd06877    4 RVSIPYVeMRRDPSNG--ERIYVFCieverndrRAKGHEpqhWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRRIFGPK 81

                         90       100
                 ....*....|....*....|..
gi 568996463 373 DAKFVEERRKQLQSYLRSVMNK 394
Cdd:cd06877   82 SYEFLESKREIFEEFLQKLLQK 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463 315 GKAANAFHVYQVYIR-----IKDDEWNVYRRYTEFRALHHQLQSAFPQvRAYSFPP----------KKAIGNKD---AKF 376
Cdd:cd07281   12 GDGMNAYVVYKVTTQtsllmFRSKHFTVKRRFSDFLGLYEKLSEKHSQ-NGFIVPPppeksligmtKVKVGKEDsssAEF 90

                         90
                 ....*....|....*..
gi 568996463 377 VEERRKQLQSYLRSVMN 393
Cdd:cd07281   91 LERRRAALERYLQRIVS 107

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463 304 INVWIPSVFL-RGKAANAFHVYQVYIRIKDDEWNVYRRYTEFRALHHQLQSAFpqvRAYSFPPKKaIGNKDAKFVEERRK 382
Cdd:cd06880    1 IEVSIPSYRLeVDESEKPYTVFTIEVLVNGRRHTVEKRYSEFHALHKKLKKSI---KTPDFPPKR-VRNWNPKVLEQRRQ 76

                         90       100
                 ....*....|....*....|..
gi 568996463 383 QLQSYLRSVM--NKVIQMVPEF 402
Cdd:cd06880   77 GLEAYLQGLLkiNELPKQLLDF 98

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463 308 IP-SVFLRGKAANAFHVYQVYIRikddewNVYR---RYTEFRALHHQLQSAFPQVRAYSFPPKKaIGNKDAKFVEERRKQ 383
Cdd:cd06885    4 IPdTQELSDEGGSTYVAYNIHIN------GVLHcsvRYSQLHGLNEQLKKEFGNRKLPPFPPKK-LLPLTPAQLEERRLQ 76

                 ....*...
gi 568996463 384 LQSYLRSV 391
Cdd:cd06885   77 LEKYLQAV 84

The phosphoinositide binding Phox Homology domain of uncharacterized plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463 294 SDFEISNRALIN--VWIPSVFLRGKAANAFHVYQVYIRIKD---DEWNVYRRYTEFRALHHQLQSAFPQVRAYSFPPKKA 368
Cdd:cd06879   17 SDGKAINPKVGNmsVVYSEYQPLNNAVDKFYRVQVGVQSPEgitTMRGVLRRFNDFLKLHTDLKKLFPKKKLPAAPPKGL 96

                         90       100
                 ....*....|....*....|....*..
gi 568996463 369 IGNKDAKFVEERRKQLQSYLRSVMNKV 395
Cdd:cd06879   97 LRMKNRALLEERRHSLEEWMGKLLSDI 123

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; 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. 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. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568996463 337 VYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ-LQSYLRSVMnkviQMVPEFA 403
Cdd:cd06884   36 VFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQdIQQFLNSLF----KMAEEVS 99

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568996463 337 VYRRYTEFRALHHQLQ------SAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLR 389
Cdd:cd06893   53 VNRRFREFLTLQTRLEenpkfrKIMNVKGPPKRLFDLPFGNMDKDKIEARRGLLETFLR 111

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 568996463 317 AANAFHVYQVYIRIKD-----DEWNVYRRYTEFRALHHQLQSAFPqvrAYSFPPK------KAIGNKDAKFVEERRKQLQ 385
Cdd:cd06865   19 GGPPYISYKVTTRTNIpsythGEFTVRRRFRDVVALADRLAEAYR---GAFVPPRpdksvvESQVMQSAEFIEQRRVALE 95

                 ....*.
gi 568996463 386 SYLRSV 391
Cdd:cd06865   96 KYLNRL 101

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568996463 337 VYRRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYlrsvMNKVIQ 397
Cdd:cd06862   34 VSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDFIEKRRERLELW----MNRLAR 90

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568996463 339 RRYTEFRALHHQLQSAFP-QVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLRSVmnkviQMVPEFAANP 406
Cdd:cd07301   40 RRYSDFERLHRRLRRLFGgEMAGVSFPRKRLRKNFTAETIAKRSRAFEQFLCHL-----HSLPELRASP 103

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568996463 339 RRYTEFRALHHQLQSAFPQVRAYSFPPKKAIGNKDAKfVEERRKQLQSYLRSVMN-KVIQ 397
Cdd:cd06886   36 RRYREFANLHQNLKKEFPDFQFPKLPGKWPFSLSEQQ-LDARRRGLEQYLEKVCSiRVIG 94