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 1720413359  70 DTVQVELIPEKKGLFLKHVEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLG-ADREFIEGRRRALK 148
Cdd:cd06866     1 DTVTVELVPEKKGLFLKHVEYEVSSKRFKSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGsADREFLEARRRGLS 80

                          90       100
                  ....*....|....*....|....*
gi 1720413359 149 RFINLVARHPPFSEDVLLKLFLSFS 173
Cdd:cd06866    81 RFLNLVARHPVLSEDELVRTFLTEP 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  70 DTVQVELIPEKKGLFLKHVEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLG-ADREFIEGRRRALK 148
Cdd:cd06866     1 DTVTVELVPEKKGLFLKHVEYEVSSKRFKSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGsADREFLEARRRGLS 80

                          90       100
                  ....*....|....*....|....*
gi 1720413359 149 RFINLVARHPPFSEDVLLKLFLSFS 173
Cdd:cd06866    81 RFLNLVARHPVLSEDELVRTFLTEP 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  77 IPEKKGLF----LKHVEYEV-------SSQRFKS---SVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLG------AD 136
Cdd:COG5391   137 NPQSLTLLvdsrDKHTSYEIitvtnlpSFQLRESrplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKKSNSeyygdrFS 216

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 137 REFIEGRRRALKRFINLVARHPPFSEDVLLKLFLSFS--GSDFLP---ADIQTQFAMSRELIRNVYNSFYKLRDRAERIA 211
Cdd:COG5391   217 DEFIEERRQSLQNFLRRVSTHPLLSNYKNSKSWESHStlLSSFIEnrkSVPTPLSLDLTSTTQELDMERKELNESTSKAI 296

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 212 SrAIDNaaDLLIFGKELSALGSD----TTPLPSWAALHLSTWGSLKQALKGLSVEFALLADRAAQQGKKEENDVVEKLNL 287
Cdd:COG5391   297 H-NILS--IFSLFEKILIQLESEeeslTRLLESLNNLLLLVLNFSGVFAKRLEQNQNSILNEGVVQAETLRSSLKELLTQ 373

                  ....*..
gi 1720413359 288 FLDLLQS 294
Cdd:COG5391   374 LQDEIKS 380

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 1720413359  70 DTVQVELIPEKKGLFLKHVEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLG-ADREFIEGRRRALK 148
Cdd:cd06866     1 DTVTVELVPEKKGLFLKHVEYEVSSKRFKSTVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGsADREFLEARRRGLS 80

                          90       100
                  ....*....|....*....|....*
gi 1720413359 149 RFINLVARHPPFSEDVLLKLFLSFS 173
Cdd:cd06866    81 RFLNLVARHPVLSEDELVRTFLTEP 105

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 1720413359  71 TVQVELIPEKKGLFLKHVEYEVSSQRF---KSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA-DREFIEGRRRA 146
Cdd:cd06093     1 SVSIPDYEKVKDGGKKYVVYIIEVTTQggeEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNlDPEFIEERRKQ 80

                          90       100
                  ....*....|....*....|....*
gi 1720413359 147 LKRFINLVARHPPFSEDVLLKLFLS 171
Cdd:cd06093    81 LEQYLQSLLNHPELRNSEELKEFLE 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  77 IPEKKGLF----LKHVEYEV-------SSQRFKS---SVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLG------AD 136
Cdd:COG5391   137 NPQSLTLLvdsrDKHTSYEIitvtnlpSFQLRESrplVVRRRYSDFESLHSILIKLLPLCAIPPLPSKKSNSeyygdrFS 216

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 137 REFIEGRRRALKRFINLVARHPPFSEDVLLKLFLSFS--GSDFLP---ADIQTQFAMSRELIRNVYNSFYKLRDRAERIA 211
Cdd:COG5391   217 DEFIEERRQSLQNFLRRVSTHPLLSNYKNSKSWESHStlLSSFIEnrkSVPTPLSLDLTSTTQELDMERKELNESTSKAI 296

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 212 SrAIDNaaDLLIFGKELSALGSD----TTPLPSWAALHLSTWGSLKQALKGLSVEFALLADRAAQQGKKEENDVVEKLNL 287
Cdd:COG5391   297 H-NILS--IFSLFEKILIQLESEeeslTRLLESLNNLLLLVLNFSGVFAKRLEQNQNSILNEGVVQAETLRSSLKELLTQ 373

                  ....*..
gi 1720413359 288 FLDLLQS 294
Cdd:COG5391   374 LQDEIKS 380

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 1720413359   88 VEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLG----ADREFIEGRRRALKRFINLVARHPPFS-E 162
Cdd:smart00312  17 IEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGrlnnFSEEFIEKRRRGLEKYLQSLLNHPELInH 96

                   ....*....
gi 1720413359  163 DVLLKLFLS 171
Cdd:smart00312  97 SEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; 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 consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720413359 100 SVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA--DR---EFIEGRRRALKRFINLVARHPPFSEDVLLKLFL 170
Cdd:cd06860    38 SVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGllDRfspEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 193 IRNVYNSFYKLRDRAERIASRAIDNAADLLIFGKELSALGSDTTPLPSWAalhlstwgslkqaLKGLSVEFALLADRAAQ 272
Cdd:cd07307     2 LDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDLSNTD-------------LGEALEKFGKIQKELEE 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 273 QGKKEENDVVEKlnlFLDLLQSYKDlcerHEKGVLHKHQRALHKyglmKRQMMSAAHGRE---PESVEQLESRIVEQENV 349
Cdd:cd07307    69 FRDQLEQKLENK---VIEPLKEYLK----KDLKEIKKRRKKLDK----ARLDYDAAREKLkklRKKKKDSSKLAEAEEEL 137

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720413359 350 IQTMELRNYFSLYCLHQETQLVHVYLPLTSHILGAFVNSQIQGHKEMSKVWNDLKP 405
Cdd:cd07307   138 QEAKEKYEELREELIEDLNKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLP 193

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  81 KGLfLKHVEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA-DREFIEGRRRALKRFINLVARHPP 159
Cdd:cd06862    15 KGL-KSFIAYQITPTHTNVTVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRfEEDFIEKRRERLELWMNRLARHPV 93

                          90
                  ....*....|....
gi 1720413359 160 FSEDVLLKLFLSFS 173
Cdd:cd06862    94 LSQSEVFRHFLTCT 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  91 EVSSQRFKSS---VYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA-----DREFIEGRRRALKRFINLVARHPPFSE 162
Cdd:cd07284    26 KTSRSEFDSSefeVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGmverfNEDFIETRRKALHKFLNRIADHPTLTF 105

                  ....*....
gi 1720413359 163 DVLLKLFLS 171
Cdd:cd07284   106 NEDFKIFLT 114

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  87 HVEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRM-VPALPPKRVLGA-DREFIEGRRRALKRFINLVARHPPFSEDV 164
Cdd:cd07285    20 YIEYQLTPTNTNRSVNHRYKHFDWLYERLLVKFGLAIpIPSLPDKQVTGRfEEEFIKMRMERLQAWMTRMCRHPVISESE 99

                  ....*...
gi 1720413359 165 LLKLFLSF 172
Cdd:cd07285   100 VFQQFLNF 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  90 YEVSSQRFKSSVY---------------RRYNDFVVFHEVLLHKFPYrMVPALPPKRVLGA--DREFIEGRRRALKRFIN 152
Cdd:cd07276    11 YEVMEERARFTVYkirvenkvgdswfvfRRYTDFVRLNDKLKQMFPG-FRLSLPPKRWFKDnfDPDFLEERQLGLQAFVN 89

                          90
                  ....*....|....*...
gi 1720413359 153 LVARHPPFSEDVLLKLFL 170
Cdd:cd07276    90 NIMAHKDIAKCKLVREFF 107

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  87 HVEYEVSSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA-DREFIEGRRRALKRFINLVARHPPFSEDVL 165
Cdd:cd07286    20 YISYKLVPSHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRfEEDFISKRRKGLIWWMDHMCSHPVLARCDA 99

                          90
                  ....*....|.
gi 1720413359 166 LKLFLSFSGSD 176
Cdd:cd07286   100 FQHFLTCPSTD 110

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 181 DIQTQFAMSRELIRNVYNSFYKLRDRAERIASRAIDNAADLLIFGKELSALG-SDTTPLpswaalhlstwGSLKQALKGL 259
Cdd:cd07596     1 EEDQEFEEAKDYILKLEEQLKKLSKQAQRLVKRRRELGSALGEFGKALIKLAkCEEEVG-----------GELGEALSKL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359 260 SVEFALLADRAAQQGKKEENDVVEKLNLFLDLLQSYKDLCERHEKgVLHKHQRALHKYGLMKRQM--MSAAHGREPESVE 337
Cdd:cd07596    70 GKAAEELSSLSEAQANQELVKLLEPLKEYLRYCQAVKETLDDRAD-ALLTLQSLKKDLASKKAQLekLKAAPGIKPAKVE 148

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720413359 338 QLESRIVEQEnvIQTMELRNYFSLYC---------LHQETQLVhvylpLTShILGAFVNSQIQGHKEMSKVWNDLKP 405
Cdd:cd07596   149 ELEEELEEAE--SALEEARKRYEEISerlkeelkrFHEERARD-----LKA-ALKEFARLQVQYAEKIAEAWESLLP 217

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 1720413359  99 SSVYRRYNDFVVFHEVLlHKFPYRMVPALPPKRVLGA----------DREFIEGRRRALKRFINLVARHPPFSEDVLLKL 168
Cdd:cd06894    38 SSVRRRYSDFEWLRSEL-ERDSKIVVPPLPGKALKRQlpfrgddgifEEEFIEERRKGLETFINKVAGHPLAQNEKCLHM 116

                  ..
gi 1720413359 169 FL 170
Cdd:cd06894   117 FL 118

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  91 EVSSQRFKSSVYRRYNDFVVFHEVLLHKFPyRMVPALPPKRVLGA--DREFIEGRRRALKRFINLVARHP 158
Cdd:cd06870    26 VVSVGRSSWFVFRRYAEFDKLYESLKKQFP-ASNLKIPGKRLFGNnfDPDFIKQRRAGLDEFIQRLVSDP 94

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; 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. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720413359 100 SVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA--DR---EFIEGRRRALKRFINLVARHPPFSEDVLLKLFLS 171
Cdd:cd07283    38 SVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGvvDRfseEFVETRRKALDKFLKRIADHPVLSFNEHFNVFLT 114

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720413359 100 SVYRRYNDFVVFhEVLLHKFPYRMVPA-LPPKRVLGA-DREFIEGRRRALKRFINLVARHPPFSEDVLLKLFLS 171
Cdd:cd06877    45 SVLRRYNEFYVL-ESKLTEFHGEFPDApLPSRRIFGPkSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLS 117

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 1720413359  87 HVEYEVSSQRFK---------SSVYRRYNDFVVFHEVL--LHKFPYR--MVPALPPKRVLGA-DREFIEGRRRALKRFIN 152
Cdd:cd06881    17 YTEYKITSKVFSrsvpedvseVVVWKRYSDFKKLHRELsrLHKQLYLsgSFPPFPKGKYFGRfDAAVIEERRQAILELLD 96

                          90
                  ....*....|....*..
gi 1720413359 153 LVARHPPFSEDVLLKLF 169
Cdd:cd06881    97 FVGNHPALYQSSAFQQF 113

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  87 HVEYEVSSQRF--KSSVYRRYNDFVVFHEVLLHKFPyrMVPAL--PPKRVLGA-DREFIEGRRRA----LKRFINLVARH 157
Cdd:cd06874    18 HFEFEVKITVLdeTWTVFRRYSRFRELHKTMKLKYP--EVAALefPPKKLFGNkSERVAKERRRQletyLRNFFSVCLKL 95

                  .
gi 1720413359 158 P 158
Cdd:cd06874    96 P 96

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains 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. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720413359 101 VYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVL-GADREFIEGRRRALKRFINLV 154
Cdd:cd06873    43 VYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFnNLDRAFLEKRRKMLNQYLQSL 97

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  77 IPEKKGLFLKHVEYEvsSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGA--DREFIEGRRRALKRFINLV 154
Cdd:cd06884    14 DPEKYYVYVVEVTRE--NQASPQHVFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRsnIKSVAEKRKQDIQQFLNSL 91

                  ....*
gi 1720413359 155 ARHPP 159
Cdd:cd06884    92 FKMAE 96

The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  87 HVEYEV----SSQRFKSSVYR-----------RYNDFVVFHEVLLHKFPYRMVPALPPKRVLGADREfIEGRRRALKRFI 151
Cdd:cd06868    20 HVLYQIvvvtRLAAFKSAKHKeedvvqfmvskKYSEFEELYKKLSEKYPGTILPPLPRKALFVSESD-IRERRAAFNDFM 98

                          90
                  ....*....|....*....
gi 1720413359 152 NLVARHPPFSEDVLLKLFL 170
Cdd:cd06868    99 RFISKDEKLANCPELLEFL 117

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720413359  91 EVSSQRFKSSVYRRYNDFVVFHEVLL--HKFPYRMvpaLPPKRVLG-ADREFIEGRRRALKRFINLV 154
Cdd:cd06875    23 EVKVGSVEWTVKHRYSDFAELHDKLVaeHKVDKDL---LPPKKLIGnKSPSFVEKRRKELEIYLQTL 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720413359  86 KHVEYEV------SSQRFKSSVYRRYNDFVVFHEVLLHKFPYRMVPALPPKRVLGAD--REFIEGRRRALKRFINLV 154
Cdd:cd07300    17 KHVVYQIiviqtgSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNfsEEIIAERRVALRDYLTLL 93

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. The specific function of SNX12 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  98 KSSVYRRYNDFVVFHEVLlHKFPYRMVPALPPKRVLGA----------DREFIEGRRRALKRFINLVARHPPFSEDVLLK 167
Cdd:cd07294    39 ESCVRRRYSDFEWLKNEL-ERDSKIVVPPLPGKALKRQlpfrgdegifEESFIEERRQGLEQFINKIAGHPLAQNERCLH 117

                  ...
gi 1720413359 168 LFL 170
Cdd:cd07294   118 MFL 120

The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; 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. p47phox is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity. The PX domain of p47phox is also involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413359  77 IPEKKGLFLKHVEYEVSSQRFkssVYRRYNDFVVFHEVLLHKFP---------YRMVPALPPKRVLGADREfIEGRRRAL 147
Cdd:cd06887    14 VPSQHYVYMFLVKWQDLSEKL---VYRRFTEIYEFHKTLKEMFPieagdinkeNRIIPHLPAPKWFDGQRA-AENRQGTL 89