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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 537 NLRITGTITAREHSGTGFHPYTLYTVKYETVLNGENS-----SGLQQLAYHTVNRRYREFLNLQTRLEEKPDLRKFIkNV 611
Cdd:cd06893     1 NIRIPKTITAKEYKGTGTHPYTLYTVQYETILDVQSEqnpnaASEQPLATHTVNRRFREFLTLQTRLEENPKFRKIM-NV 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720429855 612 KGPKKLFPDLPFGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFLALN 664
Cdd:cd06893    80 KGPPKRLFDLPFGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEFLAYG 132

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 844 WLCTESM---QKFLHIIFGTLVQRWLEVQVANLTCPQRWAQYLHLLRESIWPGGVLPKfPRPGRTQAQKAATEKQALQSL 920
Cdd:pfam08628   1 WLRRRALnalKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPGGLLAE-PPPERTEEEKLRTRKEARKLL 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1720429855 921 MDLLPDFLVEILGVNKCRLSWSLVLESFQQP 951
Cdd:pfam08628  80 LSLIPDALGSVVGRENAREAARRVFDMLQNP 110

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 537 NLRITGTITAREHSGTGFHPYTLYTVKYETVLNGENS-----SGLQQLAYHTVNRRYREFLNLQTRLEEKPDLRKFIkNV 611
Cdd:cd06893     1 NIRIPKTITAKEYKGTGTHPYTLYTVQYETILDVQSEqnpnaASEQPLATHTVNRRFREFLTLQTRLEENPKFRKIM-NV 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720429855 612 KGPKKLFPDLPFGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFLALN 664
Cdd:cd06893    80 KGPPKRLFDLPFGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEFLAYG 132

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855  97 QLEQEINRTIQMIIRDFVLSWYRSVSHEPAFEAEMEAAMKGLVQELRRRMSIVD-SHALTQRVLTLCGCHLQSYIQAKEA 175
Cdd:pfam02194   3 EVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDlASLLLSRLLPLLTSHLEDYRKAEEA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 176 TAKEQscPVQPSQLWDAYCQVTAPHPAMSC--------PTTEVTYARGIVNLILKELVPKPHLETRTGRHVVVEVITCNV 247
Cdd:pfam02194  83 VRGKK--LNELDLALASKYLALKPHPALSPvllsssqsREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 1720429855 248 ILPLISKLSDPDWIHLILVSI 268
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

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 1720429855  544 ITAREHSGTGFHPYTLYTVKYETVLngenssglqqlAYHTVNRRYREFLNLQTRLeekpdLRKFiknvkgPKKLFPDLP- 622
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGL-----------EEWTVSRRYSDFLELHSKL-----KKHF------PRSILPPLPg 58

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1720429855  623 ------FGNMDSDRVEARKSLLESFLKQLCAIPEIGN-SEEVQEFL 661
Cdd:smart00312  59 kklfgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 537 NLRITGTITAREHSGTGFHPYTLYTVKYETVLNGENS-----SGLQQLAYHTVNRRYREFLNLQTRLEEKPDLRKFIkNV 611
Cdd:cd06893     1 NIRIPKTITAKEYKGTGTHPYTLYTVQYETILDVQSEqnpnaASEQPLATHTVNRRFREFLTLQTRLEENPKFRKIM-NV 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720429855 612 KGPKKLFPDLPFGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFLALN 664
Cdd:cd06893    80 KGPPKRLFDLPFGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEFLAYG 132

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855  97 QLEQEINRTIQMIIRDFVLSWYRSVSHEPAFEAEMEAAMKGLVQELRRRMSIVD-SHALTQRVLTLCGCHLQSYIQAKEA 175
Cdd:pfam02194   3 EVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDlASLLLSRLLPLLTSHLEDYRKAEEA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 176 TAKEQscPVQPSQLWDAYCQVTAPHPAMSC--------PTTEVTYARGIVNLILKELVPKPHLETRTGRHVVVEVITCNV 247
Cdd:pfam02194  83 VRGKK--LNELDLALASKYLALKPHPALSPvllsssqsREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 1720429855 248 ILPLISKLSDPDWIHLILVSI 268
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

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 1720429855 537 NLRITGTITAREhsgtGFHPYTLYTVKYETvlngenssglQQLAYHTVNRRYREFLNLQTRLEEKpdlrkfiknvkGPKK 616
Cdd:cd06093     1 SVSIPDYEKVKD----GGKKYVVYIIEVTT----------QGGEEWTVYRRYSDFEELHEKLKKK-----------FPGV 55

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1720429855 617 LFPDLP----FGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFL 661
Cdd:cd06093    56 ILPPLPpkklFGNLDPEFIEERRKQLEQYLQSLLNHPELRNSEELKEFL 104

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 577 QQLAYHTVNRRYREFLNLQTRLEEKPDLRKFiknvkgpkklfPDLP----FGNMDSDRVEARKSLLESFLKQLCAIPEIG 652
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKFPSVII-----------PPLPpkrwLGRYNEEFIEKRRKGLEQYLQRLLQHPELR 72

                  ....*....
gi 1720429855 653 NSEEVQEFL 661
Cdd:pfam00787  73 NSEVLLEFL 81

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 586 RRYREFLNLQTRLeekpdlrkfiknvkgpKKLFPDLPFGNMDS--------DRVEARKSLLESFLKQLCAIPEIGNSEEV 657
Cdd:cd06886    36 RRYREFANLHQNL----------------KKEFPDFQFPKLPGkwpfslseQQLDARRRGLEQYLEKVCSIRVIGESDIM 99

                  ....*
gi 1720429855 658 QEFLA 662
Cdd:cd06886   100 QDFLS 104

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 1720429855 556 PYTLYTVKYETvlngenssglqQLAYHTVNRRYREFLNLQTRLEekPDLRKFIKnVKGPKKLFpdLPFGNMDSDRVEARK 635
Cdd:cd06897    14 PYTVYNIQVRL-----------PLRSYTVSRRYSEFVALHKQLE--SEVGIEPP-YPLPPKSW--FLSTSSNPKLVEERR 77

                          90       100       110
                  ....*....|....*....|....*....|
gi 1720429855 636 SLLESFLKQLCAIPE--IGNSEEVQEFLAL 663
Cdd:cd06897    78 VGLEAFLRALLNDEDsrWRNSPAVKEFLNL 107

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 584 VNRRYREFLNLQTRLeeKPDLRKFIKNVKGPKKLFpdlpFGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFLAL 663
Cdd:cd07279    38 IERRYSDFLKLYKAL--RKQHPQLMAKVSFPRKVL----MGNFSSELIAERSRAFEQFLGHILSIPNLRDSKAFLDFLQG 111

                  .
gi 1720429855 664 N 664
Cdd:cd07279   112 P 112

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 1720429855 551 GTGFHPYTLYTVKYETVLNGENSSGLQqlayhtVNRRYREFLNLQTRLEEK---------PDlrkfiKNVKGpkKLFPDL 621
Cdd:cd06859    12 GDGMSAYVVYRVTTKTNLPDFKKSEFS------VLRRYSDFLWLYERLVEKypgrivpppPE-----KQAVG--RFKVKF 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1720429855 622 PFgnmdsdrVEARKSLLESFLKQLCAIPEIGNSEEVQEFL 661
Cdd:cd06859    79 EF-------IEKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 535 IQNLRITG-TITAREHSGTGfhpYTLYTVKYETvlngENSSGLQQLAYhtvnRRYREFLNLQTRLEE--KPDLRKFIknv 611
Cdd:cd07280     2 ATDVNVGDyTIVGGDTGGGA---YVVWKITIET----KDLIGSSIVAY----KRYSEFVQLREALLDefPRHKRNEI--- 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1720429855 612 kgpkklfPDLP--------FGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFL 661
Cdd:cd07280    68 -------PQLPpkvpwydsRVNLNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEFL 118

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 583 TVNRRYREFLNLQTRL--EEKPDlrkfiKNVKGPKKLfpdlpFGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEF 660
Cdd:cd06875    32 TVKHRYSDFAELHDKLvaEHKVD-----KDLLPPKKL-----IGNKSPSFVEKRRKELEIYLQTLLSFFQKTMPRELAHF 101

                  .
gi 1720429855 661 L 661
Cdd:cd06875   102 L 102

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 533 VVIQNLRItgtitareHSGTGFHPYTLYTVKYETvlngeNSSGLQqLAYHTVNRRYREFLNLQTRLEEKPDLRKfiknvk 612
Cdd:cd06898     2 VEVRDPRT--------HKEDDWGSYTDYEIFLHT-----NSMCFT-LKTSCVRRRYSEFVWLRNRLQKNALLIQ------ 61

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1720429855 613 gPKKLFPDLPFGNMDSDR-VEARKSLLESFLKQLCAIPEI 651
Cdd:cd06898    62 -LPSLPPKNLFGRFNNEGfIEERQQGLQDFLEKVLQTPLL 100

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 540 ITGTITAREHSGTGfhpYTLYTVKyetvLNGenssglqqlAYH-TVnrRYREFLNLQtrleEKpdLRKFIKNVKG----P 614
Cdd:cd06885     4 IPDTQELSDEGGST---YVAYNIH----ING---------VLHcSV--RYSQLHGLN----EQ--LKKEFGNRKLppfpP 59

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1720429855 615 KKLFPdlpfgnMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFL 661
Cdd:cd06885    60 KKLLP------LTPAQLEERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 537 NLRITGTItAREHSGTGFHPYTLYTVKYETvlngenSSGLQQLAYhtvnRRYREFLNLQTRLEEkpdlRKFIKNVKGPK- 615
Cdd:cd06882     1 DVAVSATI-ADIEEKRGFTNYYVFVIEVKT------KGGSKYLIY----RRYRQFFALQSKLEE----RFGPEAGSSAYd 65

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720429855 616 KLFPDLP----FGNmDSDRVEARKSLLESFLKQLCAIP-EIGNSEEVQEFL 661
Cdd:cd06882    66 CTLPTLPgkiyVGR-KAEIAERRIPLLNRYMKELLSLPvWVLMDEDVRLFF 115

The phosphoinositide binding Phox Homology domain of uncharacterized fungal 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 577 QQLAYHTVNRRYREFLNLQTRLeekpdLRKFiknvkgPKKLFPDLPFGNMdSDRVEARKSLlESFLKQLCAIPEIGNSEE 656
Cdd:cd06869    45 EEYRTIYVARRYSDFKKLHHDL-----KKEF------PGKKLPKLPHKDK-LPREKLRLSL-RQYLRSLLKDPEVAHSSI 111

                  ....*
gi 1720429855 657 VQEFL 661
Cdd:cd06869   112 LQEFL 116

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 1720429855 543 TITAREHSGTGFHPYTLYTVKYETVLNGENSSGLQqlayhtVNRRYREFLNLQTRLEEK-------PDLRKFIknVKGPK 615
Cdd:cd07284     4 TVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFE------VRRRYQDFLWLKGRLEEAhptliipPLPEKFV--MKGMV 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1720429855 616 KLFPDlpfgnmdsDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFL 661
Cdd:cd07284    76 ERFNE--------DFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720429855 547 REHSGTGfHPYTLYTVKyetVLngenSSGLQqlayHTVNRRYREFLNLQTRleekpdLRKFIKNvkgpkklfPDLPfgnm 626
Cdd:cd06880    10 LEVDESE-KPYTVFTIE---VL----VNGRR----HTVEKRYSEFHALHKK------LKKSIKT--------PDFP---- 59

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1720429855 627 dSDRV--------EARKSLLESFLKQLCAIPEIgnSEEVQEFLALNT 665
Cdd:cd06880    60 -PKRVrnwnpkvlEQRRQGLEAYLQGLLKINEL--PKQLLDFLGVRH 103

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 1720429855 583 TVNRRYREFLNLQTRLeekpdLRKFiknvkgPKKLFPDLP----FGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQ 658
Cdd:cd06862    33 TVSRRYKHFDWLYERL-----VEKY------SCIAIPPLPekqvTGRFEEDFIEKRRERLELWMNRLARHPVLSQSEVFR 101

                  ...
gi 1720429855 659 EFL 661
Cdd:cd06862   102 HFL 104

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 1720429855 583 TVNRRYREFLNLQTRLEEkpdlrkfIKNVKGPKKLFPDLPFGNMDSDRVEARKSLLESFLKQLCAIPEIGNSEEVQEFL 661
Cdd:cd06877    45 SVLRRYNEFYVLESKLTE-------FHGEFPDAPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFL 116