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 568914960 121 LLFEVTSANVVKDPPSKGAsgkLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAE 200
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYV---LYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAE 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568914960 201 TIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 235
Cdd:cd07301   78 TIAKRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 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 568914960 121 LLFEVTSANVVKDPPSKGAsgkLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAE 200
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYV---LYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAE 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568914960 201 TIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 235
Cdd:cd07301   78 TIAKRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 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 568914960   160 QISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRL---RRNFTAETIARRSRAFEQFLGHLQAVPELRQA-PDLQDFF 232
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 568914960 216 LQAVPELRQAPDLQDFFVLPELRRAQSLTCTGLYREALALWANAWQLQtqlgtpsgPDRPLlTLAGLAVCHQELEDPGEA 295
Cdd:COG3914   61 ALAAGEAAAAAAALLLLAALLELAALLLQALGRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEA 131

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568914960 296 RACSEKALQLLGDkrphpflapFLEAHVRLSWRLGLDKRQSEAqLQALQEA 346
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 568914960 121 LLFEVTSANVVKDPPSKGAsgkLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAE 200
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYV---LYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAE 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568914960 201 TIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLP 235
Cdd:cd07301   78 TIAKRSRAFEQFLCHLHSLPELRASPAFLEFFYLR 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 568914960 121 LLFEVTSANVVKDPPSKGAsgkLYTLAVMGPGPPDRQPAQISRRYSDFERLHRNLQRQFRGPMSAISFPRKRLRRNFTAE 200
Cdd:cd07300    1 LLFEIPSARIIEQTISKHV---VYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEE 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568914960 201 TIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVLPEL 237
Cdd:cd07300   78 IIAERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914960  154 PDRQPAQISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFF 232
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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914960 130 VVKDPPSKGASGKLYTLAVMGP---GPPDRQPAQISRRYSDFERLHRNLQR-----QFRGPMSAisFPRKRLRRNFTAET 201
Cdd:cd06881    6 TVTDTRRHKKGYTEYKITSKVFsrsVPEDVSEVVVWKRYSDFKKLHRELSRlhkqlYLSGSFPP--FPKGKYFGRFDAAV 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568914960 202 IARRSRAFEQFLGHLQAVPELRQAPDLQDFFV 233
Cdd:cd06881   84 IEERRQAILELLDFVGNHPALYQSSAFQQFFE 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 568914960 163 RRYSDFERLHRNLQRQFrgPMSAISFPRKR-LRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFFVL 234
Cdd:cd07276   39 RRYTDFVRLNDKLKQMF--PGFRLSLPPKRwFKDNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFFCL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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 568914960 153 PPDRQPAQISRRYSDFERLH-------RNL-QRQFRGPmsaiSFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQ 224
Cdd:cd07288   32 PEDVKEVVVWKRYSDLKKLHgelaythRNLfRRQEEFP----PFPRAQVFGRFEAAVIEERRNAAEAMLLFTVNIPALYN 107

                 ....*...
gi 568914960 225 APDLQDFF 232
Cdd:cd07288  108 SPQLKEFF 115

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568914960 161 ISRRYSDFERLHRNLQRQFrGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAV 219
Cdd:cd06874   34 VFRRYSRFRELHKTMKLKY-PEVAALEFPPKKLFGNKSERVAKERRRQLETYLRNFFSV 91

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 568914960 154 PDRQPAQISRRYSDFERLHRNLQRQ--FRGPMSAISfPRKRLRR----NFTAETIARRSRAFEQFLGHLQAVPELRQAPD 227
Cdd:cd06893   46 QPLATHTVNRRFREFLTLQTRLEENpkFRKIMNVKG-PPKRLFDlpfgNMDKDKIEARRGLLETFLRQLCSIPEISNSEE 124

                 ....*..
gi 568914960 228 LQDFFVL 234
Cdd:cd06893  125 VQEFLAY 131

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914960 123 FEVTsanvVKDPPSKG---ASGKLYTLAVMGPGPPDRQPA-QISRRYSDFERLHRNLQRQFRG----PMsaisfPRKRLR 194
Cdd:cd06861    1 FEIT----VGDPHKVGdltSAHTVYTVRTRTTSPNFEVSSfSVLRRYRDFRWLYRQLQNNHPGvivpPP-----PEKQSV 71

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568914960 195 RNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 231
Cdd:cd06861   72 GRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLF 108

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 568914960 161 ISRRYSDFERLHRNLQRQFRGPMSAiSFPRKR--LRRNFTAETIARRSRAFEQFLGHL--QAVPELRQAPDLQDFFVLP 235
Cdd:cd06897   31 VSRRYSEFVALHKQLESEVGIEPPY-PLPPKSwfLSTSSNPKLVEERRVGLEAFLRALlnDEDSRWRNSPAVKEFLNLP 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914960 152 GPPDRQPAQISRRYSDFERLHRNLqRQFRGPMSAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDF 231
Cdd:cd06877   37 KGHEPQHWSVLRRYNEFYVLESKL-TEFHGEFPDAPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDF 115

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 568914960 123 FEVTSANVVKDPPSKGAsgKLYTLAVMGPGPPDRQpaqISRRYSDFERLHRNLQRQFrgPMSAI-SFPRKRLRRNFTAET 201
Cdd:cd06862    1 YHCTVTNPKKESKFKGL--KSFIAYQITPTHTNVT---VSRRYKHFDWLYERLVEKY--SCIAIpPLPEKQVTGRFEEDF 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568914960 202 IARRSRAFEQFLGHLQAVPELRQAPDLQDFfvlpelrraqsLTCT 246
Cdd:cd06862   74 IEKRRERLELWMNRLARHPVLSQSEVFRHF-----------LTCT 107

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX 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. 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 568914960 163 RRYSDFERLHRNLQRQFrgPMSAI-SFPRK-RLRR----NFTAETIARRSRAFEQFLGHLQAVPELRQAPDLQDFF 232
Cdd:cd06863   42 RRYSDFVFLHECLSNDF--PACVVpPLPDKhRLEYitgdRFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. 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. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914960 140 SGKLYTLAVMGPGPPdrQPAQISRRYSDFERLHRNLQRQFrgPMSAI-SFP-RKRLRRNFTAETIARRSRAFEQFLGHLQ 217
Cdd:cd06883   15 KYYIYVVKVTRENQT--EPSFVFRTFEEFQELHNKLSLLF--PSLKLpSFPaRVVLGRSHIKQVAERRKIELNSYLKSLF 90

                         90
                 ....*....|....*....
gi 568914960 218 AVPELRQAPDLQDFFVLPE 236
Cdd:cd06883   91 NASPEVAESDLVYTFFHPL 109

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568914960  237 LRRAQSLTCTGLYREALALWANAWQLQTQLGtpsGPDRPLL--TLAGLAVCHQELEDPGEARACSEKALQLL 306
Cdd:pfam13424   7 NNLAAVLRRLGRYDEALELLEKALEIARRLL---GPDHPLTatTLLNLGRLYLELGRYEEALELLERALALA 75

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 568914960 158 PAQISRRYSDFERLHRNLQRQFRG----------PMSAISFPRKRLRRNFtaetIARRSRAFEQFLGH------LQAVPE 221
Cdd:cd07280   38 SIVAYKRYSEFVQLREALLDEFPRhkrneipqlpPKVPWYDSRVNLNKAW----LEKRRRGLQYFLNCvllnpvFGGSPV 113

                         90
                 ....*....|....
gi 568914960 222 LRQapdlqdfFVLP 235
Cdd:cd07280  114 VKE-------FLLP 120

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568914960 161 ISRRYSDFERLHRNLQRQFrgP-MSAISFPRKRLRRNFTAETIARRSRAFEQFLGHL-----QAVPELRQAPD 227
Cdd:cd07277   34 VYRRYSEFYELHKKLKKKF--PvVRSFDFPPKKAIGNKDAKFVEERRKRLQVYLRRVvntliQTSPELTACPS 104

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568914960 201 TIARRSRAFEQFLGHLQAVpeLRQAPDlqdfFVLPELRRAQSLTCTGLYREALALWANAWQLQtqlgtpsgPDRPLLtLA 280
Cdd:COG3914  120 NLLLALGRLEEALAALRRA--LALNPD----FAEAYLNLGEALRRLGRLEEAIAALRRALELD--------PDNAEA-LN 184

                         90       100
                 ....*....|....*....|....*
gi 568914960 281 GLAVCHQELEDPGEARACSEKALQL 305
Cdd:COG3914  185 NLGNALQDLGRLEEAIAAYRRALEL 209

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568914960 161 ISRRYSDFERLHRNLQRQFRG---PmsaiSFPRK-RLRRnftaetiaRRSR-AFEQFLGHLQAVPELRQAPDLQDFF 232
Cdd:cd06869   52 VARRYSDFKKLHHDLKKEFPGkklP----KLPHKdKLPR--------EKLRlSLRQYLRSLLKDPEVAHSSILQEFL 116