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 568957575  73 LLFEIASARIEERKVSKFVMYQVVVIQTGSFDSDKAVVERRYSDFERLQKALLKRFGPELEDVAFPRKRLTGNLSAETIC 152
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568957575 153 ERRRELREYLRLLYAVRAVRRSREFLDFLTRPEL 186
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568957575  73 LLFEIASARIEERKVSKFVMYQVVVIQTGSFDSDKAVVERRYSDFERLQKALLKRFGPELEDVAFPRKRLTGNLSAETIC 152
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568957575 153 ERRRELREYLRLLYAVRAVRRSREFLDFLTRPEL 186
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568957575  103 FDSDKAVVERRYSDFERLQKALLKRFgPELEDVAFPRKRLTGNLSAETICERRRELREYLRLLYAVRAVRRSREFLDFLT 182
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKF-PSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLE 82

                  ..
gi 568957575  183 RP 184
Cdd:pfam00787  83 SD 84

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568957575  73 LLFEIASARIEERKVSKFVMYQVVVIQTGSFDSDKAVVERRYSDFERLQKALLKRFGPELEDVAFPRKRLTGNLSAETIC 152
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568957575 153 ERRRELREYLRLLYAVRAVRRSREFLDFLTRPEL 186
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568957575  73 LLFEIASARIEERKVSKFVMYQVVVIQTGSFDSDKAVVERRYSDFERLQKALLKRFGPELEDVAFPRKRLTGNLSAETIC 152
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                         90       100
                 ....*....|....*....|....*...
gi 568957575 153 ERRRELREYLRLLYAVRAVRRSREFLDF 180
Cdd:cd07301   81 KRSRAFEQFLCHLHSLPELRASPAFLEF 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568957575  46 PSSNSSMTTRELQEHWQKEKSRwKHvRLLFEIASARIEERKVS--------KFVMYQVV----VIQTGSFDSDKAVVERR 113
Cdd:COG5391  101 FRSLRDMLSLLLPTSLQPPLST-SH-TILDYFISSTVSNPQSLtllvdsrdKHTSYEIItvtnLPSFQLRESRPLVVRRR 178

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568957575 114 YSDFERLQKALLKRFG----PELedvafPRKRLTGNLS 147
Cdd:COG5391  179 YSDFESLHSILIKLLPlcaiPPL-----PSKKSNSEYY 211

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
                 ....*....|....*....|....*....|....*....|....*....|
gi 568957575  84 ERKVSKFVMYQVVvIQTGSFDSDKAVVERRYSDFERLQKALLKRFGPELE 133
Cdd:cd07280   16 DTGGGAYVVWKIT-IETKDLIGSSIVAYKRYSEFVQLREALLDEFPRHKR 64

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568957575  80 ARIEERKVskFVMYQVVVIQTGSFDSDKAVVERRYSDFERLQKALLKRFGPELEDVAFPR 139
Cdd:cd06882    9 ADIEEKRG--FTNYYVFVIEVKTKGGSKYLIYRRYRQFFALQSKLEERFGPEAGSSAYDC 66

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568957575    86 KVSKFVMYQVVViqtgSFDSDKAVVERRYSDFERLQKALLKRFgPELEDVAFPRKRLTGNL 146
Cdd:smart00312  10 GKHYYYVIEIET----KTGLEEWTVSRRYSDFLELHSKLKKHF-PRSILPPLPGKKLFGRL 65

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568957575  89 KFVMYQVvviqtgSFDSDKAVVERRYSDFERLQKALLKRFG----PELedvafPRKRLTGNLSAETI 151
Cdd:cd06866   17 KHVEYEV------SSKRFKSTVYRRYSDFVWLHEYLLKRYPyrmvPAL-----PPKRIGGSADREFL 72