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 1720396605   1 MGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDL 80
Cdd:cd07301    26 IQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIAKRSRAFEQFLCHLHSLPELRASPAF 105

                  ....*..
gi 1720396605  81 QDFFVLP 87
Cdd:cd07301   106 LEFFYLR 112

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 1720396605   1 MGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDL 80
Cdd:cd07301    26 IQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIAKRSRAFEQFLCHLHSLPELRASPAF 105

                  ....*..
gi 1720396605  81 QDFFVLP 87
Cdd:cd07301   106 LEFFYLR 112

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720396605   12 QISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRL---RRNFTAETIARRSRAFEQFLGHLQAVPELRQA-PDLQDFF 84
Cdd:smart00312  29 TVSRRYSDFLELHSKLKKHF--PRSILpPLPGKKLfgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELINHsEVVLEFL 104

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396605  68 LQAVPELRQAPDLQDFFVLPELRRAQSLTCTGLYREALALWANAWQLQtqlgtpsgPDRPLlTLAGLAVCHQELEDPGEA 147
Cdd:COG3914    61 ALAAGEAAAAAAALLLLAALLELAALLLQALGRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEA 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720396605 148 RACSEKALQLLGDkrphpflapFLEAHVRLSWRLGLDKRQSEAqLQALQEA 198
Cdd:COG3914   132 LAALRRALALNPD---------FAEAYLNLGEALRRLGRLEEA-IAALRRA 172

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 1720396605   1 MGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDL 80
Cdd:cd07301    26 IQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIAKRSRAFEQFLCHLHSLPELRASPAF 105

                  ....*..
gi 1720396605  81 QDFFVLP 87
Cdd:cd07301   106 LEFFYLR 112

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 1720396605   4 GPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 83
Cdd:cd07300    29 GSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIAERRVALRDYLTLLYSLRFVRRSQAFQDF 108

                  ....*.
gi 1720396605  84 FVLPEL 89
Cdd:cd07300   109 LTHPEL 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396605   6 PDRQPAQISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFF 84
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKF--PSVIIpPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720396605  13 ISRRYSDFERLHRNLQR-----QFRGPMSAisFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFV 85
Cdd:cd06881    40 VWKRYSDFKKLHRELSRlhkqlYLSGSFPP--FPKGKYFGRFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720396605  15 RRYSDFERLHRNLQRQFrgPMSAISFPRKR-LRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVL 86
Cdd:cd07276    39 RRYTDFVRLNDKLKQMF--PGFRLSLPPKRwFKDNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFFCL 109

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720396605  12 QISRRYSDFERLHRNLQRQFRG----PMsaisfPRKRL--RRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 83
Cdd:cd06859    38 SVLRRYSDFLWLYERLVEKYPGrivpPP-----PEKQAvgRFKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLF 110

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396605  13 ISRRYSDFERLHRNLQRQFrGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQD 82
Cdd:cd06873    43 VYRRYSDFHDLHMRLKEKF-PNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQE 111

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 1720396605   6 PDRQPAQISRRYSDFERLHRNLQRQ--FRGPMSAISfPRKRLRR----NFTAETIARRSRAFEQFLGHLQAVPELRQAPD 79
Cdd:cd06893    46 QPLATHTVNRRFREFLTLQTRLEENpkFRKIMNVKG-PPKRLFDlpfgNMDKDKIEARRGLLETFLRQLCSIPEISNSEE 124

                  ....*..
gi 1720396605  80 LQDFFVL 86
Cdd:cd06893   125 VQEFLAY 131

The phosphoinositide binding Phox Homology domain of yeast MDM1p; 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. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720396605  13 ISRRYSDFERLHRNLQRQFrGPMSAISFPRKRL--RRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 83
Cdd:cd06876    59 VARRYSEFLELHKYLKKRY-PGVLKLDFPQKRKisLKYSKTLLVEERRKALEKYLQELLKIPEVCEDEEFRKF 130

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720396605  13 ISRRYSDFERLHRNLQRQFRGPMSAiSFPRKR--LRRNFTAETIARRSRAFEQFLGHL--QAVPELRQAPDLQDFFVLP 87
Cdd:cd06897    31 VSRRYSEFVALHKQLESEVGIEPPY-PLPPKSwfLSTSSNPKLVEERRVGLEAFLRALlnDEDSRWRNSPAVKEFLNLP 108

The phosphoinositide binding Phox Homology domain of RPK118-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 bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396605   5 PPDRQPAQISRRYSDFERLHRNL----QRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDL 80
Cdd:cd07287    32 PEDVQEIVVWKRYSDFKKLHKDLwqihKNLCRQSELFPPFAKAKVFGRFDESVIEERRQCAEDLLQFSANIPALYNSSQL 111

                  ....
gi 1720396605  81 QDFF 84
Cdd:cd07287   112 EDFF 115

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720396605  11 AQISRRYSDFERLHRNLQRQFRG----PMsaisfPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 83
Cdd:cd06861    37 FSVLRRYRDFRWLYRQLQNNHPGvivpPP-----PEKQSVGRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLF 108

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396605  68 LQAVPELRQAPDLQDFFVLPELRRAQSLTCTGLYREALALWANAWQLQtqlgtpsgPDRPLlTLAGLAVCHQELEDPGEA 147
Cdd:COG3914    61 ALAAGEAAAAAAALLLLAALLELAALLLQALGRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEA 131

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720396605 148 RACSEKALQLLGDkrphpflapFLEAHVRLSWRLGLDKRQSEAqLQALQEA 198
Cdd:COG3914   132 LAALRRALALNPD---------FAEAYLNLGEALRRLGRLEEA-IAALRRA 172

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720396605  12 QISRRYSDFERLHRNLqRQFrgPMSAISFPRKR-LRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 83
Cdd:cd06872    34 VVKRRFRNFETLHRRL-KEV--PKYNLELPPKRfLSSSLDGAFIEERCKLLDKYLKDLLVIEKVAESHEVWSF 103

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 1720396605  10 PAQISRRYSDFERLHRNLQRQFRG----------PMSAISFPRKRLRRNFtaetIARRSRAFEQFLGHLQAVPELRQAPD 79
Cdd:cd07280    38 SIVAYKRYSEFVQLREALLDEFPRhkrneipqlpPKVPWYDSRVNLNKAW----LEKRRRGLQYFLNCVLLNPVFGGSPV 113

                  ....
gi 1720396605  80 LQDF 83
Cdd:cd07280   114 VKEF 117

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 1720396605  12 QISRRYSDFERLHRNLQRQFRG----PMSAISFPRKRLRRnFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 83
Cdd:cd06860    38 SVRRRYQDFLWLRQKLEESHPThiipPLPEKHSVKGLLDR-FSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVF 112

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396605  53 TIARRSRAFEQFLGHLQAVpeLRQAPDlqdfFVLPELRRAQSLTCTGLYREALALWANAWQLQtqlgtpsgPDRPLLtLA 132
Cdd:COG3914   120 NLLLALGRLEEALAALRRA--LALNPD----FAEAYLNLGEALRRLGRLEEAIAALRRALELD--------PDNAEA-LN 184

                          90       100
                  ....*....|....*....|....*
gi 1720396605 133 GLAVCHQELEDPGEARACSEKALQL 157
Cdd:COG3914   185 NLGNALQDLGRLEEAIAAYRRALEL 209

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 1720396605   3 PGPPDRQpaqISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQ 81
Cdd:cd06862    27 PTHTNVT---VSRRYKHFDWLYERLVEKY--SCIAIpPLPEKQVTGRFEEDFIEKRRERLELWMNRLARHPVLSQSEVFR 101

                          90
                  ....*....|....*..
gi 1720396605  82 DFfvlpelrraqsLTCT 98
Cdd:cd06862   102 HF-----------LTCT 107