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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418515  66 QPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFFVLPE 145
Cdd:COG3914    5 ALLALAALAAAALLAAAAAAELALAAELEAAALAAALGLALLLLAALAEAAAAALLALAAGEAAAAAAALLLLAALLELA 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418515 146 LRRAQSLtctGLYREALALWANAWQLQaqlgtpsgPDRPLlTLAGLAVCHQELEDPGEARACCEKALQLLGDkslhplla 225
Cdd:COG3914   85 ALLLQAL---GRYEEALALYRRALALN--------PDNAE-ALFNLGNLLLALGRLEEALAALRRALALNPD-------- 144

                        170       180       190
                 ....*....|....*....|....*....|
gi 530418515 226 pFLEAHVRLSWRLGLDKRQSEArLQALQEA 255
Cdd:COG3914  145 -FAEAYLNLGEALRRLGRLEEA-IAALRRA 172

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418515   69 QISRRYSDFERLHRNLQRQFrgPMAAI-SFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 141
Cdd:pfam00787  10 SVRRRYSDFVELHKKLLRKF--PSVIIpPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418515  65 CQPAQISRRYSDFERLHRNLQRQFrgPMAAIS-FPRKRL-----RRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQ 138
Cdd:COG5391  170 SRPLVVRRRYSDFESLHSILIKLL--PLCAIPpLPSKKSnseyyGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYKNSK 247

                 ..
gi 530418515 139 DF 140
Cdd:COG5391  248 SW 249

Tetratricopeptide repeat;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418515  146 LRRAQSLTCTGLYREALALWANAWQLQAQLGtpsGPDRPLL--TLAGLAVCHQELEDPGEARACCEKALQLL 215
Cdd:pfam13424   7 NNLAAVLRRLGRYDEALELLEKALEIARRLL---GPDHPLTatTLLNLGRLYLELGRYEEALELLERALALA 75

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 530418515  37 LFLLPWAWVISDKPQ---LYTLAVIGPGPPDCQPAQISRRYSDFERLHRNLQRQFRGPMAAISFPRKRLRRNFTAETIAR 113
Cdd:cd07279    2 KFEIVSARTVKEGEKkyvVYQLAVVQTGDPDTQPAFIERRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAE 81

                         90       100       110
                 ....*....|....*....|....*....|.
gi 530418515 114 RSRAFEQFLGHLQAVPELRHAPDLQDFFVLP 144
Cdd:cd07279   82 RSRAFEQFLGHILSIPNLRDSKAFLDFLQGP 112

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418515  69 QISRRYSDFERLHRNLQRQFRGPMAAiSFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 141
Cdd:cd06093   33 TVYRRYSDFEELHEKLKKKFPGVILP-PLPPKKLFGNLDPEFIEERRKQLEQYLQSLLNHPELRNSEELKEFL 104

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 530418515    69 QISRRYSDFERLHRNLQRQFrgPMAAI-SFPRKRL---RRNFTAETIARRSRAFEQFLGHLQAVPEL-RHAPDLQDFF 141
Cdd:smart00312  29 TVSRRYSDFLELHSKLKKHF--PRSILpPLPGKKLfgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELiNHSEVVLEFL 104

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 530418515  72 RRYSDFERLHRNLQRQFrgPMAAISFPRKR-LRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFFVL 143
Cdd:cd07276   39 RRYTDFVRLNDKLKQMF--PGFRLSLPPKRwFKDNFDPDFLEERQLGLQAFVNNIMAHKDIAKCKLVREFFCL 109

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418515  72 RRYSDFERLHRNLQRQFrgPMAAISFPRKRL-RRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 141
Cdd:cd06870   38 RRYAEFDKLYESLKKQF--PASNLKIPGKRLfGNNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

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 530418515  69 QISRRYSDFERLHRNLQRQFRG----PMaaisfPRKRL--RRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDF 140
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 530418515  70 ISRRYSDFERLHRNLQRQFrGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQD 139
Cdd:cd06873   43 VYRRYSDFHDLHMRLKEKF-PNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQE 111

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 530418515  70 ISRRYSDFERLHRNLQRQFRGPMAAiSFPRKR--LRRNFTAETIARRSRAFEQFLGHL--QAVPELRHAPDLQDFFVLP 144
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 530418515  62 PPDCQPAQISRRYSDFERLHRNL----QRQFRGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDL 137
Cdd:cd07287   32 PEDVQEIVVWKRYSDFKKLHKDLwqihKNLCRQSELFPPFAKAKVFGRFDESVIEERRQCAEDLLQFSANIPALYNSSQL 111

                 ....
gi 530418515 138 QDFF 141
Cdd:cd07287  112 EDFF 115

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 530418515  70 ISRRYSDFERLHRNLQRQFrGPMAAISFPRKRL--RRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDF 140
Cdd:cd06876   59 VARRYSEFLELHKYLKKRY-PGVLKLDFPQKRKisLKYSKTLLVEERRKALEKYLQELLKIPEVCEDEEFRKF 130

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 530418515  68 AQISRRYSDFERLHRNLQRQFRG----PMaaisfPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDF 140
Cdd:cd06861   37 FSVLRRYRDFRWLYRQLQNNHPGvivpPP-----PEKQSVGRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLF 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418515  69 QISRRYSDFERLHRNLqRQFRGPMAAISFPRKRLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDF 140
Cdd:cd06877   45 SVLRRYNEFYVLESKL-TEFHGEFPDAPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDF 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418515  70 ISRRYSDFERLHRNLQRQFrgPMAAIS-FPRK-RLRRnftaetiaRRSR-AFEQFLGHLQAVPELRHAPDLQDFF 141
Cdd:cd06869   52 VARRYSDFKKLHHDLKKEF--PGKKLPkLPHKdKLPR--------EKLRlSLRQYLRSLLKDPEVAHSSILQEFL 116

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 530418515  69 QISRRYSDFERLHRNLqRQFrgPMAAISFPRKR-LRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDF 140
Cdd:cd06872   34 VVKRRFRNFETLHRRL-KEV--PKYNLELPPKRfLSSSLDGAFIEERCKLLDKYLKDLLVIEKVAESHEVWSF 103

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 530418515  48 DKPQLYTLAVIGPGPPdcQPAQISRRYSDFERLHRNLQRQFrgPMAAI-SFP-RKRLRRNFTAETIARRSRAFEQFLGHL 125
Cdd:cd06883   14 EKYYIYVVKVTRENQT--EPSFVFRTFEEFQELHNKLSLLF--PSLKLpSFPaRVVLGRSHIKQVAERRKIELNSYLKSL 89

                         90       100
                 ....*....|....*....|
gi 530418515 126 QAVPELRHAPDLQDFFVLPE 145
Cdd:cd06883   90 FNASPEVAESDLVYTFFHPL 109

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 530418515  72 RRYSDFERLHRNLQRQFrgPMAAI-SFPRK-RLRR----NFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFF 141
Cdd:cd06863   42 RRYSDFVFLHECLSNDF--PACVVpPLPDKhRLEYitgdRFSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFL 115

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 530418515  70 ISRRYSDFERLHRNLQRQFrgP-MAAISFPRKRLRRNFTAETIARRSRAFEQFLGHL-----QAVPELRHAPD 136
Cdd:cd07277   34 VYRRYSEFYELHKKLKKKF--PvVRSFDFPPKKAIGNKDAKFVEERRKRLQVYLRRVvntliQTSPELTACPS 104

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. 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 is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418515  68 AQISRRYSDFERLHRNLQRQFRGpmaAISFPRK-----RLRRNFTAETIARRSRAFEQFLGHLQAVPELRHAPDLQDFFV 142
Cdd:cd06865   42 FTVRRRFRDVVALADRLAEAYRG---AFVPPRPdksvvESQVMQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLT 118

                 ..
gi 530418515 143 LP 144
Cdd:cd06865  119 LQ 120